Here, we take a closer look at injuries as well as diseases that might lead to back-of-knee pain.

Injury-Related Causes of Pain Behind Knee

1. Hamstring injury

Inflammation or tearing of one of the tendons of the hamstring muscles can cause pain behind the knee cap. The most common tendon behind knee pain is the biceps femoris tendon, which can become injured in activities such as kick-boxing, downhill running, or sprinting. The pain is usually sudden in onset and localized to the back of the knee, where the tendon attaches to the bone. After the initial injury, the pain may become a dull ache that quickly intensifies with sudden movements. Some mild swelling behind the knee also may be present. Treatment involves the combination referred to as “RICE”:

• Resting the knee
• Icing the back of the knee
• Compression knee bandages or braces
• Elevation of the knee, particularly after the initial injury

Nonsteroidal anti-inflammatory drugs (NSAIDs) may be helpful for pain control. Some people may benefit from physical therapy exercises to strengthen leg muscles. (See also Knee Pain Remedies: Start with Classic “RICE” Advice and Knee Joint Pain Solutions, from Strengthening Exercises to Surgery to Alternative Treatments.)

2. Meniscus tear

Both a sudden twisting of the knee and long-term overuse can cause tears in either of the menisci, two crescent-shaped pieces of cartilage in the knee. These tears can cause pain, a “locking” sensation in the knee, swelling, and difficulty with knee extension. Treatment is similar to that of a hamstring injury (RICE and NSAIDs), although some individuals may require surgical repair of the meniscus.

3. Posterior Cruciate Ligament (PCL) injury

The PCL is one of the strongest ligaments in the knee and helps provide stability to the back of the knee. Injury causing a sprain or tear of the PCL is not as common as injuries of other knee ligaments but can occur when the knee is overextended or if there is a forceful blow to the front of a bent knee (such as might occur in a car accident). Pain and swelling behind the knee may result as well as joint instability. Because the PCL often heals well on its own, treatment is usually nonsurgical and includes a RICE regimen, NSAIDs for pain relief, and immobilization of the knee with bandages or braces. Surgery is usually only indicated if there is a concomitant injury such as a knee dislocation.

Disease-Related Causes of Pain Behind Knee

1. Osteoarthritis

Osteoarthritis (OA) is a disease characterized by degeneration of the cartilage that provides cushioning between the bones of our joints. It commonly affects the weight-bearing joints of the body like the knee, causing pain (often worse at night), stiffness, and swelling. OA can cause knee joint pain, including pain behind knee cap. Treatment includes NSAIDs and cyclooxygenase 2 inhibitor drugs (COX 2 inhibitors) to reduce inflammation and provide pain control, physical therapy to strengthen the supporting muscles of the leg, and sometimes steroid injections into the knee joint. For severe OA, total knee replacement may be indicated.

2. Rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune disease in which the body’s immune system attacks the synovial lining of joints causing inflammation and often distortion and destruction of the affected joints. As with OA, RA can cause pain in any aspect of the knee including the back of the knee, but, unlike OA which may only affect one knee, RA most often involves both knees. Symptoms include pain (usually worse in the morning), swelling, and stiffness. Treatment can include NSAIDs, COX 2 inhibitors, steroids, or disease-modifying antirheumatic drugs (DMARDs).

3. Gout

Gout is a disease characterized by the build-up of the waste product uric acid in the blood of affected individuals. The uric acid can form crystals that deposit in joints causing a painful “attack” or flare. When the crystals deposit in the knee, the knee can become swollen, red, and warm. Pain can occur behind the knee but also in any other part of the knee. Treatment involves pain control with NSAIDs or the drug colchicine and the use of uric acid-lowering medications as well as the adoption of a gout diet low in purine-rich foods which can contribute to uric acid levels.

Injury or Disease-Related Back of Knee Pain Causes

1. Popliteal Cyst

A popliteal cyst, also called a Baker’s cyst, is a localized swelling behind the knee that occurs secondary to an injury or an inflammatory disease. As fluid builds up in the knee joint, it can bulge out into a ball-shaped protrusion behind the knee. While it can be painless in some people, it may cause back of the knee pain in others and often causes a decrease in range of motion, particularly with knee flexion. Specific treatment of the cyst is usually not needed. Treating the underlying injury or disease is more often indicated. Rarely, the cyst is drained or surgically removed if it is particularly large.

Life-Threatening Causes of Pain Behind the Knee

1. Deep vein thrombosis

A deep vein thrombosis (DVT) is a blood clot that develops in a vein. They most often occur in the large veins of the thigh or calf and, therefore, can cause pain behind knee cap. A variety of factors can put someone at increased risk of a DVT including trauma, prolonged sitting, cardiovascular disease, or family history of DVT. DVTs behind the knee will often cause localized pain, swelling, tenderness, redness, and warmth. Because the clot can break free and travel to the lung, where it can cause a life-threatening blockage in a lung artery (pulmonary embolus or PE), DVTs represent a medical emergency. Treatment involves the use of blood thinners such as warfarin or surgical removal.

2. Tumor

Tumors are a rare cause of pain behind the knee but should be considered as a cause if other conditions have been ruled out. Liposarcomas (malignant tumors of fat tissue), synovial sarcomas (malignant tumors of synovial tissue), and osteosarcomas (malignant bone tumors) are tumors that can be found behind the knee. Benign (non-malignant) tumors such as osteochondroma can also occur in the knee. A bulging mass in the knee that may be accompanied by systemic symptoms of weight loss, night sweats, or fever can be signs and symptoms of malignant tumors in the knee. Treatment varies depending on the specific tumor but may include chemotherapy, radiation, or surgery.

Originally published in 2016, this post is regularly updated.

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Geriatricians. These physicians, who have done additional training in geriatrics after a residency in internal medicine, specialize in caring for older adults and preventing and treating diseases and disabilities that tend to occur later in life. Geriatricians treat Alzheimer’s disease, as well as medical issues that may complicate memory problems in older adults, such as Parkinson’s disease, cardiovascular issues, or chronic obstructive pulmonary disease.

Neurologists. These specially trained physicians diagnose and treat disorders of the nervous system. They focus on diseases of the brain, spinal cord, nerves, and nerve centers, and are often consulted for neurological and memory problems such as Parkinson’s disease, multiple sclerosis, and Alzheimer’s disease. Neurologists are particularly knowledgeable about brain regions and their role in physical and mental functioning.

Geriatric Psychiatrists. These physicians specialize in caring for the mental and emotional health of older adults. Their extensive medical training has given them a thorough knowledge of the complex relationship between emotional illness and other medical illnesses in older individuals. They are well qualified to distinguish between physical and psychological causes of disorders, and are expert at dealing with memory problems that involve psychiatric issues, such as major depression, anxiety, agitation, or psychotic symptoms such as delusions.

Neuropsychologists. Neuropsychologists hold PhD degrees in psychology. They specialize in the psychological assessment and treatment of mental and nervous disorders that are more typical in older adults. Geriatric neuropsychologists focus on issues involving memory, competency, depression, anxiety, or adjustment difficulties. Through testing and therapy, they help older adults who experience anxiety, depression, or other psychological problems associated with memory loss.

Research Trials

One way to get access to groundbreaking memory disorder treatments, at no cost to you, is to enroll in a research trial offered by one of the major medical institutions in your area (see “Clinical Trial Resources”). A clinical trial is a research study that uses human volunteers in a controlled manner to determine whether new therapies are safe and effective.

People who enroll in clinical trials may benefit from their participation, but they also must be aware that there is risk, since these treatments are not yet proven. It is also possible that they won’t receive the treatment being studied but instead a placebo. These trials, however, are often the only access to cutting-edge therapy options not yet available to the public, and they give participants the opportunity to receive care from top-tier providers.

By working directly with medical researchers, you also can learn about the latest medical advances. And participating in a clinical trial gives you an opportunity to help improve the health of others who might benefit from new treatments in the future.

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Alzheimer’s Disease Education & Referral Center
www.nia.nih.gov/alzheimers
800-438-4380

Alzheimer’s Foundation of America (AFA)
www.alzfdn.org
866-232-8484
322 Eighth Ave., 7th Fl.
New York, NY 10001

American Federation for Aging Research (AFAR)
www.afar.org
888-582-2327
55 West 39th St.,16th Fl.
New York, NY 10018

National Institute of Mental Health (NIMH)
www.nimh.nih.gov
866-615-6464
6001 Executive Blvd., Rm 6200, MSC 9663
Bethesda, MD 20892-9663

National Institute on Aging
www.nia.nih.gov
800-222-2225
Bldg 31, Rm 5C27
31 Center Dr., MSC 2292
Bethesda, MD 20892

National Institute of Neurological Disorders and Stroke
www.ninds.nih.gov
800-352-9424
P.O. Box 5801
Bethesda, MD 20824

National Parkinson Foundation
www.parkinson.org
800-473-4636)
1359 Broadway, Suite 1509
New York, NY 100018

US Government Caregiver Support
https://www.usa.gov/disability-caregiver
800-872-4681

U.S. Department of Health & Human Services
www.hhs.gov
877-696-6775
200 Independence Ave., SW
Washington, D.C. 20201

Centers for Medicare and Medicaid Services (CMS)
medicare.gov
7500 Security Boulevard
Baltimore, MD 21244-1850
800-633-4227

National Center for Assisted Living
ncal.org
1201 L St. NW
Washington, DC 20005
202-842-4444

Alzheimer’s Association
Alz.org
225 N. Michigan Ave., Fl 17
Chicago, IL 60601
800-272-3900

Agencies That Help Caregivers

The American Society for Aging lists agencies that offer help for caregivers. Reaching out to theseorganizations and having discussions with your own primary care doctor can be important to your own health.

Although it can be difficult to admit, you have to consider your own care in order to care for your  loved one. Visit them at https://www.asaging.org

AARP
https://www.aarp.org/caregiving
877-434-7598

Alzheimer’s Association
https://www.alz.org/help-support/caregiving
800-272-3900

Alzheimer’s Foundation

Caregiving Resources

866-232-8484

American Association of Caregiving Youth
https://www.aacy.org
800-508-9618

Caregiver Action Network
https://caregiveraction.org
202-454-3970

Caregiver Support Services
http://caregiversupportservices.com
866-201-6896

Caring.Com
www.caring.com
800-973-1540

Caring Bridge
www.caringbridge.org
651-452-7940

Eldercare Locator
https://eldercare.acl.gov
800-677-1116

Family Caregiver Alliance
https://www.caregiver.org
800-445-8106

Home Instead Senior Care
https://www.homeinstead.com
888-331-1023

National Alliance for Caregiving

Home

301-718-8444

National Adult Day Services Association

National Adult Day Services Association: Innovation, Service, and Support

877-745-1440

National Family Caregiver Support Program
https://acl.gov/programs/performance-older-americans-act-programs
800-677-1116

National Institute on Aging’s National Alzheimer’s Education and Referral Center
https://www.nia.nih.gov/health/alzheimers
800-438-4380

National Long-Term Care Clearinghouse

National Adult Day Services Association: Innovation, Service, and Support

800-677-1116

Rosalynn Carter Institute for Caregiving

home

229-928-1234

VA Caregiver Support
https://www.caregiver.va.gov
844-698-2311

Well Spouse Association
https://wellspouse.org
732-577-8899

The post Resources appeared first on University Health News.

Alzheimer’s disease: The most common form of dementia. Memory, thinking, and behavior become progressively worse until a person requires help with most aspects of daily functioning.

amyloid plaque: In the brains of people with Alzheimer’s disease, protein pieces called beta-amyloid clump together to form a material called amyloid plaque. This impairs the ability of brain cells to function properly.

amyloid precursor protein (APP): The beta-amyloid that clumps together to form amyloid plaques is a small piece of this protein.

antibodies: These components of the immune system attack harmful substances in the body.

apolipoprotein E (ApoE): A gene that provides instructions for making a protein that is also called apolipoprotein E. The protein is involved in the transport of fats in the body. People who carry an allele of the ApoE gene called ApoE4 are at increased risk for Alzheimer’s disease.

beta-amyloid: Pieces of protein that can stick together to form amyloid plaques in the brains of people with Alzheimer’s disease.

biomarker: Something that can be measured in the body that indicates the presence or absence of disease or the risk for later developing a disease.

central nervous system: The part of the nervous system made up of the brain and spinal cord.

cerebellum: The part of the brain related to movement, balance, and emotion.

cerebral cortex: The outermost layer of the brain, the cerebral cortex is responsible for higher brain functions, such as intelligence, personality, and planning and organizing.

cerebrospinal fluid: The brain and spinal cord are surrounded by this clear fluid, which acts as a cushion.

cholinesterase inhibitors: These Alzheimer’s disease drugs act on a neurotransmitter (chemicals that facilitate communication between brain cells) called acetylcholine. Acetylcholine is diminished in people with Alzheimer’s disease. Cholinesterase inhibitor drugs (such as donepezil, rivastigmine, and galantamine) stop cholinesterase from deactivating acetylcholine, thus allowing more acetylcholine to remain in the brain.

cognition: This refers to mental functions such as memory, orientation, language, judgment, and problem solving.

dementia: An acquired loss of cognitive function that is serious enough to interfere with independent functioning. Typical dementias are progressive over time, and include disturbance in memory and executive function (planning and organizing). Dementia is a symptom of Alzheimer’s disease. There are several other causes (or types) of dementia.

deoxyribonucleic acid (DNA): This is the hereditary material inside of cells. Genes are composed of DNA.

gene: Genes code for physical traits like eye and hair color as well as many other functions of living organisms. Genes are made up of DNA. Each chromosome inside the nucleus (center) of a cell contains many genes. These are the basic units of heredity.

glucose: A sugar used by the body as a source of energy. Food that is eaten is broken down in the digestive system into glucose.

hippocampus: This brain structure plays an important role in memory. In people with Alzheimer’s disease the hippocampus shrinks considerably.

immune system: The immune system is a complex system that defends the body against attacks by foreign invaders. It can recognize potentially dangerous substances (such as bacteria and viruses) and mount attacks via specialized cells.

inflammation: When tissues of the body are injured by trauma, bacteria, heat, or other causes, inflammation (swelling) occurs. This is a response of the immune system that helps with getting rid of foreign substances and with healing. Sometimes inflammation persists beyond the time when it is useful, or occurs without a provoking threat, and can be harmful.

Lewy body dementia: One of several forms of dementia. Lewy bodies are microscopic proteins that can accumulate in the brain and cause mental decline. People with this type of dementia also have other symptoms, such as drowsiness, lethargy, visual hallucinations, physical rigidity, and loss of spontaneous movement.

magnetic resonance imaging (MRI): This diagnostic test uses a powerful magnet and radio waves to produce a highly detailed three-dimensional image of an internal body area. An MRI of the brain may be performed in people with suspected dementia.

mild cognitive impairment: Problems with memory, language and other mental functions that are more pronounced than normal age-related changes but don’t interfere significantly with everyday function.

mini-mental state examination (MMSE): A short test that measures a person’s basic cognitive health, including short-term memory, long-term memory, writing, and speaking.

neurons (also called nerve cells): There are numerous types of cells in the human body. The brain and spinal cord are composed of nerve cells. This type of cell has a cell body, several short branches (dendrites), and one long branch (axon). Nerve cells send signals (via neurotransmitters) down the axon, which are picked up by connecting cells at the dendrites.

neurotransmitter: These are chemicals that allow cells in the brain to communicate with one another.

Parkinson’s disease: In people with this disease brain cells that produce a neurotransmitter called dopamine are diminished. Dopamine-producing cells are essential for movement. People with Parkinson’s disease typically have a tremor or shake at rest, that can affect the hands, arms, legs, and face. They also have stiffness in the limbs, slow movement, and impaired balance and coordination. Some people with Parkinson’s disease develop dementia, especially late in the course.

placebo: An inactive substance used in clinical trials of new drugs. In these studies, one group of patients will receive the drug being tested and a second group will receive the placebo. By comparing the two groups, scientists can determine if the drug being tested worked.

tau: A type of protein that is involved in brain structure; in Alzheimer’s disease, collapsed tau proteins form tangles that accumulate as the disease progresses.

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Although the analogy is a bit of a stretch, it can be helpful to think about your brain, or your memory, as a muscle—the earlier you start working and training it, the better (and longer) the outcome. In this chapter, we outline some suggestions that may help you organize information, imprint it in your mind, and hopefully recall it more easily.

Build Basic Memory Skills

Some of these simple approaches may help make information easier to retain and recall, while others may help mitigate the impact of memory loss:

Focus. Devote your attention to one memory task at a time. You’ll have an easier time fixing the information in your mind and recalling it later if you have given it your full attention.

Manage Your Memory. Try to organize the information you want to recall into separate categories that make sense to you. This might help overloading your memory with too much information at once. Take breaks during the process of remembering to give your brain a rest.

Make an Effort. To remember something, you have to put in some work. Get motivated to remember by considering how the information will be useful to you. For example, memorizing the names of your medications will enable you to discuss them more easily with your doctor at appointments.

Associate. Connect new pieces of information with things you already know. For example, if you meet a new neighbor named Carol, think “Carol Burnett” to help you remember her name the next time you run into her.

Use Mnemonic Strategies and Other Memory Techniques. Organize information into rhymes, acronyms, or other forms that are easier for your brain to encode and recall. For example, make a rhyme out of a friend’s neighborhood gate code that you have trouble remembering. “1024 opens the door.”

Understand the Information You Are Trying to Remember. If you’re trying to learn how to use the Bluetooth on your new car, try to understand how each step in the process works. You’ll be more likely to remember how to do something if you know the reason for it. Then practice repeating the steps to cement them in your mind.

Train, Rehearse, and Practice. If you have trouble concentrating, practice focusing on one subject or task for 10 minutes without letting your mind wander. The next day, increase your concentration time to 12 or 15 minutes, gradually building your ability to focus and ignore distractions. Or, challenge your power of concentration by reading a news article with the television on. Play online brain-training games (such as seniorbrains.com) to boost your brain’s processing speed. Instead of just humming along to the lyrics of your favorite song, try to memorize them.

Say it Out Loud. Some people are more auditory than others and may benefit from saying information they want to be certain to remember out loud. The sound of the words may be easier to recall than the visual of them written down. Even better, say it several times, as the repetition may help reinforce it.

Use Cues. Lists on your phone or on a pad are a great way to track errands you need to run or items you need to pick up, but sometimes other visual cues can serve as a good back up. If you run out of cereal, instead of automatically recycling the box, put it on your kitchen counter to remind you to pick up or order more.

Similarly, put your empty medicine bottle by the door or in your purse/briefcase to remind yourself to refill your prescription. Paste a “sticky note” on your computer screen to remind you to email your friend about dinner. Use clocks with timers to remind you to turn off the oven.

For a handy way to remember key memory strategies, see “Helpful Acronym ‘GULP’ Cues Memory Strategies.”

Train Your Brain

Regularly engaging in training exercises that help you practice specific cognitive abilities (e.g., attention or processing speed) may help protect against memory loss better than memory strategies alone. Examples of cognitive exercises you might try:

Strengthen your powers of attention by opening a book to a random page and counting the number of words without touching the page. If you lose count, begin again until you finish the page. Strengthen your ability to concentrate by introducing distractions, such as turning on a TV or music.

Boost information processing speed by looking at a picture in a magazine and trying to observe all the elements in it for one minute. Jot down all the details that you recall seeing on a piece of paper and then compare your notes to the actual picture. Or read an excerpt from a book for the same amount of time. Then make a list of all the details you can recall in the excerpt and compare it to the book section itself. As your processing speed improves, shorten the time you spend examining each new picture or reading each excerpt.

Increase your short-term memory by listening to a news update on the radio and then trying to recall all the stories covered during the music interlude or next commercial. Or if there is a story about a place you’re not familiar with, look up its major tourist attractions and try to recall those a few minutes later. As your short-term memory improves, try to remember additional details as well like the other countries it borders.

Exercise your capacity to recall information by reading a medium-length article on any subject while making an effort to remember as many details as you can. Put the article aside and write or recite as much as you can of its contents. Then check the original article to see how you did.

Use Mindfulness Meditation

Research suggests that the ability to pay attention—a key aspect of memory—declines with age. One excellent way to improve your ability to pay attention and remember is to practice mindfulness meditation. This form of meditation involves focusing your awareness on sensory stimuli in the present moment, while ignoring intrusive thoughts and inner chatter.

Mindfulness meditation can slow a racing mind, help you pay attention to information you need to learn, and improve your ability to focus without becoming distracted and jumping from thought to thought. Research suggests it may even help reverse memory loss.

Massachusetts General Hospital neuroscientist Sara Lazar, PhD, has demonstrated that older individuals who meditate have better preserved cortical regions of the brain. These regions, which are responsible for attention, sensory processing, and integrating emotional and cognitive processes, normally thin with age. Yet the regions remain thick in people who practice mindfulness meditation, an indication that performance of cognitive tasks associated with those regions is preserved.

To enjoy the benefits of mindfulness meditation, you need to practice regularly. A daily 20-minute meditation should be sufficient (see “Mindfulness Meditation Technique”).

Plan Ahead

Finding a regular time to get organized for the week to come can help you stay on top of “to do” items and avoid forgetting important upcoming events. Whether it is through a smartphone app, computer calendar, or paper calendar, note your goals, activities, appointments, and chores for each day of the week. A weekly plan will help you stay on track without cluttering your mind with minutiae. Before you start, check the previous week’s schedule and carry over any tasks you have not completed. Include emails you need to answer, bills that need to be paid, telephone calls you have to make, and so on. Think of tasks you need to accomplish, and projects you want to concentrate on for the week. Divide items into categories, such as “home,” “social activities,” “medical,” “work,” and “shopping.” And include entries such as:

Home:

• Chores (e.g., take out the trash and recycling on Tuesdays)
• Routine maintenance (e.g., change air filters on the 1st; schedule oil change for the 15th).

Social Activities

• Exercise activities (e.g., yoga class Monday, Wednesday, and Friday at 9)
• Special dates such as birthdays or anniversaries
• Social gatherings (e.g., book club on Thursday, dinner with neighbors Friday)

Medical

• Health-care provider appointments (e.g. physical therapy, blood work)
• Medication reminders (e.g. blood pressure medicine at bedtime)

At the beginning of each day, consult your weekly plan. As new tasks arise, get in the habit of recording them into your plan so that important information will be readily accessible. Cross off items you’ve accomplished. Carry the plan with you, so you’ll have it handy to refer to wherever you go.

Make Information Stand Out

Some studies suggest that confusion about previously learned information, rather than the passage of time, weakens memory and interferes with its transfer to long-term storage. To increase your ability to retain a memory, endow it with unique elements or associations so that it stands apart from other information you may be exposed to at the same time. You can use a number of imaginative techniques:

• Take a snapshot: Create a mental “photograph”—a visual record of what you want to remember. Notice as many details as possible, such as that the woman you’ve just met wears her hair in a tight bun.
• Prepare a speech: Pretend you must describe what you want to remember to someone else. Rehearsing details  out loud helps fix them in your mind.
• Sing it: Make up a jingle containing the information you’re trying to remember, such as a shopping list. “I need a dozen eggs, and some tissues for my nose. Ground beef, corn on the cob, and wart pads for my toes.” The rhythm and tune of your jingle will help fix the information in your mind so you can remember it more easily later.
• Create a vivid mental image: For example, to help you remember to buy peanut butter, spaghetti, and olives at the supermarket, try picturing yourself with peanut butter smeared in your hair, a necklace of olives, and a hula skirt made of spaghetti strands. The vivid image should make your shopping list easier to recall.

Putting it All Together

An easy way to remember the main pillars of a healthy approach to living that might reduce your odds of Alzheimer’s disease is one recommended by Dr. Tanzi of Massachusetts General. It is called SHIELD and includes:

• Work on good Sleep habits
• Keep a Handle on stress
• Interact with others
• Exercise daily
• Learn new skills
• Eat a healthy Diet

The post 9. Maximizing Memory appeared first on University Health News.

A groundbreaking Finnish study—the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) study, published in 2015—showed that a two-year interventional program of dietary changes, physical activity, cognitive training, social activity, and medical management of metabolic and vascular risk factors improved cognitive performance among those study participants, ages 60 to 77, who were randomized to the intervention compared with those who only received health advice.

Building upon these results and working in collaboration with the authors of the FINGER study, the Alzheimer’s Association launched a similar $20 million lifestyle intervention study of 2,000 60 to 79-year-old participants with a variety of risk factors for dementia in 2018, called the U.S. Study to Protect Brain Health through Lifestyle Intervention to Reduce Risk study (called the “POINTER study”). The study aims to add to the body of evidence that a substantial proportion of dementia cases could be prevented with lifestyle modifications even in individuals with pre-existing risk factors such as cardiovascular disease. It is expected to conclude in 2023.

The impact of lifestyle on dementia risk was a major theme of the 2019  Alzheimer’s Association International Conference (AAIC), with multiple encouraging studies offering hope even to those with an increased genetic risk for dementia. Among the highlights were:

• Making four or five healthy lifestyle changes (healthy diet, exercise, no smoking, light to moderate alcohol intake, and cognitive stimulation) reduces dementia risk by 60 percent compared to adopting one or no changes.
• Sticking to a healthy lifestyle (no smoking, moderate alcohol intake, healthy diet, and regular exercise) may reduce AD risk even in those at high genetic risk.
• Cognitive reserve, achieved through education and cognitive stimulation, might lower the risk of dementia among people exposed to high air pollution levels.

These build on The Lancet’s International Commission on Dementia Prevention, Intervention, and Care 2017 report that cited childhood education, aggressive blood pressure control, social engagement, smoking cessation, depression management, diabetes treatment, healthy weight maintenance, and hearing preservation as interventions that could help avoid roughly 35 percent of all dementia cases. Factors that influence heart and blood vessel health may be particularly important.

Research suggests that cerebrovascular disease may contribute to both brain atrophy and the buildup of abnormal proteins. The good news is that vascular risk factors can also be modified.

Reassess Your Diet

The food you eat is “fuel” for your entire body, the brain included. Brain cells need a rich and varied supply of vitamins and nutrients to grow and function properly, and to resist and repair damage (see “Vitamins for a Healthy Brain”). Important elements supplied by foods help protect your brain from free radicals (unstable molecules that damage brain cells through a process called oxidation) that play a role in AD and other disorders. The right foods may help boost mental energy, improve concentration, and strengthen communication between brain cells. They also may help preserve brain volume.

In a June 2018 study of over 4,400 cognitively unimpaired individuals published in the journal Neurology, Dutch researchers demonstrated that adherence to the Dutch dietary guidelines—which emphasize fruits and vegetables, fish and lean meats, nuts and legumes, and whole grains, among other healthy options—was significantly associated with larger brain volumes, including gray matter volume and hippocampal volume, both of which are known to decrease in AD.

A healthy diet also helps lower your risk for cardiovascular disease. High blood pressure, hardening of the arteries, stroke, and disease of the small blood vessels of the brain all contribute to memory decline.

Research consistently shows that a plant-based diet that’s low in fat and processed foods protects both your heart and your brain. One of the best-researched eating plans for heart and health is the Mediterranean diet, which limits meat and emphasizes fruits and vegetables, fish, and monounsaturated fats such as olive and canola oils. In addition to lowering risk for heart disease and cancer, Mediterranean-style diets are associated with a reduced risk for mild cognitive impairment (MCI).

Eating a Mediterranean diet supplemented with omega-3 fatty acid-rich olive oil or extra nuts may further enhance cognitive function, possibly because the antioxidant properties in extra-virgin olive oil help reduce oxidative stress on the body and improve circulation.

Researchers from the Mayo Clinic added support for the Mediterranean diet. In their study, published in the Journal of Alzheimer’s Disease, the researchers evaluated 278 participants ages 70 and older who were not cognitively impaired. The participants completed a food-frequency questionnaire, and each was assigned a Mediterranean Diet (MeDi) score based on how much of their food consumption was consistent with the core elements of a Mediterranean diet.

Each participant underwent amyloid positron emission tomography (PET) imaging, on average, 1.4 years after completion of the questionnaire. The study authors found that after adjusting for age, sex, education, and ApoE4 status, those individuals with a higher MeDi score had significantly lower levels of brain beta-amyloid as seen on PET scan.

Additionally, higher intake of vege­tables, vitamin A or beta-carotene from food sources, and moderate alcohol consumption were each independently associated with lower brain beta-­amyloid levels on PET imaging.

The Mediterranean style of eating (see “Mediterranean Diet”) may be particularly beneficial when it’s combined with the  Dietary Approaches to Stop Hypertension (DASH) diet used to lower high blood pressure. The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, which incorporates both styles of eating, might lower the risk of cognitive impairment by 30 to 35 percent, according to research presented at the 2017 Alzheimer’s Association International Conference.

The MIND diet includes 10 brain-healthy food groups that adherents are encouraged to eat regularly, along with five unhealthy food groups dieters are advised to limit or avoid (see “The MIND Diet”).

A study in the journal Alzheimer’s & Dementia showed that cognitive scores among adults (average age roughly 80 years old) with strict adherence to the MIND diet were equivalent to scores expected of people 7.5 years younger in age. Another study by the same researchers showed that while strict adherence to the Mediterranean, MIND, and DASH diets could reduce AD risk, even moderate adherence to the MIND diet could reduce risk. A 12-year study from Australia published in Alzheimer’s & Dementia in 2019 was the first to replicate the beneficial findings from the MIND diet outside of the U.S. This study did not find reduced odds of cognitive impairment with the Mediterranean diet.

Another diet plan that’s showing promise for halting mental decline is the Nordic Diet (see “The Nordic Diet”), which features local food favored in countries like Denmark, Finland, Iceland, Norway, and Sweden (including root vegetables, fish, and whole-grain cereals).

While it shares many of the same dietary features as the Mediterranean eating plan, the Nordic diet might be even better at protecting the heart and brain, as well as encouraging weight loss.

In a six-year study published in the February 2018 issue of Nutrients and first presented at the 2017 Alzheimer’s Association International Conference, researchers reported that among 2,223 dementia-free individuals ages 60 and older, adherence to a Nordic diet was associated with less cognitive decline than adherence to a Mediterranean diet, MIND diet, DASH diet, or the similar Baltic Sea Diet, which was created by the Finnish Heart Association, the Finnish Diabetes Association, and the University of Eastern Finland. At the 2018 AAIC, researchers presented additional data demonstrating that not only did the Nordic diet reduce cognitive decline, when combined with physical and mental activity, the reductions were even greater.

Foods for Focus

A few food groups benefit health in general and brain health in particular:

Fruits and Vegetables. When it comes to eating fruits and vegetables, the “five-a-day” rule is good advice. The World Health Organization recommends eating five servings of plant-based foods daily to improve your overall health and prevent diseases like cancer and heart disease. A 2017 Chinese study found that eating at least three servings of vegetables and two servings of fruit daily might lower the risk of dementia in older adults.

Fresh fruits and vegetables, such as spinach, strawberries, blueberries, and carrots, are high in brain-protective antioxidants. Adding more green, leafy vegetables high in vitamin K, such as spinach, kale, and collard greens, might be particularly helpful for slowing cognitive decline.

A 2018 study demonstrated that individuals whose diet was rich in plant-based polyphenols, such as nuts, citrus, berries, and leafy green vegetables in addition to soy, cereals and olive oil, had a lower risk of dementia over a 12-year period compared to those whose diet was low in these micronutrients.

Whole Grains. Whole-grain products, such as bread, cereal, pasta, and brown rice contain complex carbohydrates. These carbs provide healthy levels of the brain fuel glucose to increase energy and improve memory function.

Lean Protein. Low-fat dairy foods, nuts, seeds, and beans, and occasional servings of eggs, poultry, and lean meats provide protein that helps keep your mind alert. They also supply vitamins and other nutrients that promote the growth of new brain cells and support healthy brain functioning. Beans are loaded with magnesium, a mineral that helps regulate a key brain receptor important for learning and memory. Magnesium is found naturally in dark leafy vegetables, nuts, legumes, tofu, and whole grains.

Healthy Fats. Among the components that make the Mediterranean and MIND diets beneficial for heart and brain health are the types of fat it includes. Monounsaturated fats found in canola and olive oils can help lower levels of LDL (“bad”) cholesterol. Polyunsaturated oils, such as those derived from corn, cottonseeds, and sunflower seeds, help the body absorb vitamins. They also provide energy, which heightens alertness.

Omega-3 fatty acids appear to be especially important to brain health. Research suggests that these fatty acids, which are found in cold-water fish, as well as in flaxseeds and dark-green leafy vegetables, play a key role in cognitive health and functioning. People who eat fish at least once a week have more brain gray matter, and slower declines in memory and thinking ability than people who don’t regularly eat fish.

Regular fish eaters also appear to have reduced risk of MCI or AD. A phase 3 study conducted by researchers from the Veteran’s Administration and University of Wisconsin is looking to evaluate whether a purified form of the omega 3-fatty acid eicosapentaenoic acid (EPA), called icosapent ethyl (IPE), might improve brain blood flow, CSF biomarkers, and cognitive performance in cognitively-healthy veterans at increased risk of AD. The study has enrolled 150 participants ages 50 to 75 who will be randomized to the supplement vs. placebo and is expected to conclude in 2021.

Fluids. Consider the type of fluids you drink. Limit sodas, including diet soda, which has been linked to dementia risk. Water is a healthier option. Also consider having a cup or two of tea and/or coffee each day. Tea is rich in antioxidants and anti-inflammatory compounds that researchers say may help hold off cognitive decline—especially in people at genetic risk for dementia. The caffeine in both coffee and tea is also showing evidence of slowing mental decline. A recent study found that older women who drink two to three cups of coffee daily may be at lower risk for developing dementia or cognitive impairment.

Foods to Avoid

Caring for your brain requires not only adding nutritious foods to your diet but avoiding unhealthy foods as well. Reduce or eliminate saturated fats, such as butter and lard, and trans fats (hydrogenated or partially hydrogenated oils), which are found in many commercially prepared fried foods, processed foods, and snack foods. These unhealthy fats can raise levels of artery-clogging LDL cholesterol, and they might directly affect memory, too.

Go easy on simple carbohydrates, such as processed white rice and flour, and refined sugars, as these foods can increase your risk of developing insulin resistance, a condition that may be a contributing factor in the development of AD. Many people find that cooking at home more often helps them get the brain-healthy foods they need in their diet while avoiding the unhealthy fats and excess salt and sugar often found in prepared foods.

Watch Your Waistline

While a definitive link between body weight and memory decline has not yet been established, studies suggest that controlling your weight may be a good way to protect your brain.

A high body mass index (BMI), which measures your ratio of height to weight, is associated with poorer mental skills in older adults.

Experts aren’t sure what causes the association between weight and memory loss, but it may have to do with genetic factors. More than 33 percent of Americans carry a variant of a common gene that both increases their likelihood for obesity and makes them more vulnerable to AD. Regular exercise and a low-fat diet can minimize the effects of this gene variant.

Other research suggests that the effects of poor glucose tolerance—a common complication of obesity—may cause atrophy of the brain’s learning and memory centers in obese individuals. Low brain levels of the hormone leptin, which is associated with obesity, also may be responsible for learning and memory problems. The good news is that losing weight may help improve memory.

A complicating factor in the obesity-dementia connection is the contradictory finding that excess weight may have a protective effect in some older people. Several investigations have linked being underweight later in life with an increased risk for dementia.

Researchers at Massachusetts General Hospital and Brigham and Women’s Hospital found that seniors with the lowest BMIs have more deposits of beta-amyloid in their brains, especially if they have the ApoE4 gene variant, which raises the risk for AD. In the elderly, a very low BMI can indicate frailty, which is known to be associated with AD. Although this finding warrants further study, it underscores the idea that being underweight as you age can be as problematic as being overweight.

Engage in Exercise

The benefits of exercise for cognitive health are myriad, including warding off cognitive decline. Exercise is known to protect against conditions linked to Alzheimer’s, such as diabetes, high blood pressure, and obesity.

The ideal exercise program for both health promotion and dementia prevention combines aerobics and strength training with flexibility and balance exercises, like tai chi and yoga. Regular aerobic workouts enhance cognitive abilities by increasing the flow of oxygen-rich blood to areas of the brain responsible for learning and memory, promoting the growth of new connections between brain cells, and providing mental stimulation. Any aerobic physical exercise, from dancing to gardening, can improve brain function and lower your Alzheimer’s risk, as long as it gets your heart pumping.

Strength training—such as lifting light weights or working out with resistance bands—may improve executive function, memory, and working memory. Researchers have found that older adults who have strong muscles may be less likely to develop AD than people who are physically weak.

The earlier you start getting fit, the better. Staying active in midlife correlates with better cognition and a lower risk of developing dementia later in life (see “Midlife Cardiovascular Fitness Associated with Lower Dementia Risk in Women”). If you’ve been inactive for a while, see your doctor about designing an exercise program that’s safe for you. Start with a plan that seems manageable and aim to increase your workout as your stamina improves with a goal of 30 minutes or more of walking, swimming, or other forms of aerobic exercise at least five days a week. Even a single bout of exercise has been shown to not only improve people’s performance on cognitive testing but also improve connectivity on functional MRI.

Find activities that appeal to you. If you’ve never enjoyed running, jogging doesn’t have to be your exercise regimen. Instead, look for activities that you enjoy and vary them so that you stay engaged and avoid boredom. Remember that even household chores and gardening count as exercise. Include exercises to improve balance and coordination.

At least twice a week, strength train to boost energy, increase muscle mass, and help you burn fat faster. For maximum benefit, combine diet with exercise, brain training and social engagement. Listen to a podcast or educational program while you walk. Plan a regular exercise outing with friends. This multifaceted approach is good for overall health and may help slow cognitive decline in older adults.

Monitor Your Blood Pressure

The results of the SPRINT-MIND study demonstrate that staying on top of your blood pressure is critical to your cognitive health. Recent research suggests a lower-target blood pressure may have benefits for both cardiovascular and brain health, so talk to your doctor about what is recommended for you.

Break Bad Habits

Smoking, excessive alcohol consumption, and illicit drug use all have been linked to mental decline. If you smoke, quit. In addition to the well-known deleterious effects of smoking on the lungs and cardiovascular system, smoking has effects on the brain, which include neuron damage in the midbrain and hippocampus.

The United Kingdom’s Alzheimer’s Society reports that smoking increases an individual’s risk of developing dementia by 30 to 50 percent.

Research presented at the 2019 AAIC demonstrated that early adult to ­mid­life smoking was associated with an increased risk for cognitive impairment and that that impairment could be seen as early as age 40 —far earlier than originally suspected. Additionally, “heavy ­stable” (regular, multiple cigarettes per day) smokers were 1.5 to 2.2 times more likely to experience cognitive impairment than “quitters” or “minimal stable” (fewer cigarettes, less regular) smokers.

Chronic heavy drinking is linked to brain atrophy, impaired memory and learning, and disrupted communication between brain cells. Excessive alcohol consumption is of special concern in older adults, because with advancing age, people become increasingly vulnerable to the effects of alcohol. In an older brain, alcohol may accelerate normal aging, aggravating symptoms of cognitive decline and early dementia.

Researchers from the University of California San Francisco found that alcohol use disorder (compulsive alcohol use, loss of control over alcohol intake, and withdrawal when not using) is associated with an increased risk of dementia in women over the age of 55. So, if you drink, do so in moderation. Women should have no more than one serving of alcohol a day. Men should limit themselves to one or two servings (confirm this amount with your doctor).

Manage Your Medications

Many medications commonly prescribed to older adults have unwanted cognitive side effects. The more of these drugs you take, the higher the odds are that you’ll see some mental decline. Because your sensitivity to the effects of drugs increases with age and medications tend to linger longer in your system, side effects can show up at lower doses than they did when you were younger.

Every time you’re prescribed a new drug, weigh the risks and benefits and discuss possible side effects with your health-care provider. If the drug is known to affect cognition, ask whether you can try an alternative medication or start at a lower dose. Any decrease in cognitive function that occurs soon after you start taking a new drug or after a change in dose suggests the medication is the cause. Report these side effects to your doctor right away.

Review your list of medications—including over-the-counter drugs and supplements—with your doctor and pharmacist every year. This annual review can help you prevent unwanted side effects and dangerous interactions and weed out drugs you no longer need.

Memory-Impairing Drugs

Some drugs are known to cause iatrogenic amnesia, or drug-induced amnesia, but any drug has the potential. These include, but are not limited to:

•  Benzodiazepines used to treat anxiety and insomnia, such as lorazepam (Ativan)
• Benzodiazepine-like hypnotics used to treat anxiety, insomnia, and sleep disorders, such as zolpidem (Ambien)
• Antidepressants used to treat used to treat depression and anxiety, such as venlafaxine (Effexor), fluoxetine (Prozac), and paroxetine (Paxil, Pexeva)
• Newer anticonvulsants used to treat epileptic seizures, bipolar disorder, and nerve pain, which include gabapentin (Neurontin), lamotrigine (Lamictal), levetiracetam (Keppra), pregabalin (Lyrica), and topiramate (Topamax)
•   Other drugs to be concerned about: Isotretinoin (Accutane), which is used to treat acne; cyclosporine (Gengraf, Neoral, Sandimmune, SangCya), which are used to treat organ rejection, rheumatoid arthritis, and psoriasis; mefloquine (Larium), which is used to prevent and treat malaria; trihexyphenidyl (Artane), which is used to treat Parkinson’s disease; bupropion (Wellbutrin, Wellbutrin SR, Wellbutrin XL, Zyban, Budeprion), which is used to treat depression and seasonal affective disorder (SAD) and to help people quit smoking.

Minimize Stress

A stressful event could accelerate brain aging, according to research presented at the 2017 Alzheimer’s Association International Conference. Researchers from the University of Wisconsin studied this relationship in 1,320 adults in their 50s. They had the participants fill out questionnaires related to stressful events that occurred throughout their lifetime, and then they performed memory and problem-solving assessments on all participants. They found that the greater the number of stressful events an individual had experienced, the worse their performance on the cognitive function tests.

Feelings of pressure, tension, and distress increase levels of the stress hormone cortisol (see “How Stress and Cortisol Affect the Brain”). Excessive or prolonged elevations in cortisol can deteriorate networks of dendrites that connect neurons with one another, reducing communication among brain cells.

Long-term stress also impairs the functioning of neurotransmitters (chemicals responsible for transmitting messages from one cell to another). Stress can slow the creation of new neurons in the hippocampus to replace injured or dying cells (a process called neurogenesis), resulting in a gradual shrinkage of that key memory area. Research links shrinkage of the hippocampus with a higher risk of AD.

Stress also may activate protein kinase C, a brain enzyme that can impair functioning in the prefrontal cortex, the decision-making center of the brain responsible for short-term memory. Research implicated chronic stress as a modifier of the function of microglia, the predominant immune cells of the central nervous system and a key player in maintaining brain homeostasis or physiologic balance.

Fortunately, you may be able to protect your brain from the harmful effects of stress and reduce your risk for memory problems by learning relaxation techniques. The Relaxation Response (see “The Relaxation Response,” on page 84), developed by Herbert Benson, MD, of the Benson-Henry Institute (BHI) for Mind Body Medicine at Massachusetts General Hospital, can help lower breathing rate, blood pressure, and oxygen consumption, and may help reduce levels of oxidative stress on cells. Other stress-reducing techniques include deep-breathing exercises, yoga, tai chi, progressive relaxation, visualization, meditation, and relaxing activities such as listening to soothing music or taking a warm bath.

Try building a relaxing activity into your daily routine—whether it is a slow walk in the park, a cup of coffee outside, or a soothing bath. If you are feeling overwhelmed by stress, consider seeking help from a mental health professional.

Get Enough Sleep

Sleep is critical to vital processes ranging from immunity to growth to cellular repair and an integral part of maintaining our cognitive health. Current recommendations from the American Academy of Sleep Medicine, the National Sleep Foundation, and the American Sleep Association are for adults to get seven to nine hours of sleep a night, yet research suggests a third of American adults don’t achieve this.

During restful sleep, your brain consolidates newly acquired information and strengthens memories. A lack of sleep can make it more difficult for you to acquire memories of skills and procedures, such as how to navigate a website or ride a bike. Insufficient sleep also harms short-term memory, which is involved in temporarily storing and managing information.

More recently, research has revealed that sleep is a critical time for clearing toxins and waste from the brain. Studies have shown that the brain has a waste removal system, called the glymphatic system, that works in concert with the brain’s blood vessels, pumping cerebrospinal fluid through brain tissue to filter out waste. However, the glymphatic system is dependent on deep non-REM sleep to function optimally. Some scientists speculate that impairment of the glymphatic system due to disrupted sleep may influence clearance of beta-amyloid or tau proteins and thus explain the association between sleep deprivation and heightened risk of Alzheimer’s disease.

The quality of sleep and sleep architecture you experience changes with age. Adults ages 65 and older experience less stage IV sleep—the deep, restorative stage of sleep—than younger people. They also take longer to fall asleep and awaken more easily.

Conditions like obstructive sleep apnea and restless legs syndrome also may interrupt restful slumber. The interruption of oxygen flow caused by sleep apnea may be especially harmful to the brains of older adults. People with sleep apnea are more likely to have amyloid plaque buildup in their brains, as well as increased levels of tau protein.

Three studies presented at the 2017 Alzheimer’s Association International Conference demonstrated increased levels of these AD biomarkers in the brains of individuals with various forms of sleep-disordered breathing. In one of these studies, sleep disordered breathing among cognitively normal participants resulted in a more rapid accumulation of beta-amyloid than in controls, regardless of ApoE4 gene risk.

In a 2018 study in JAMA Neurology, researchers showed an association between significantly increased levels of beta-amyloid in the brains of cognitively normal adults ages 70 and older who experienced excessive daytime sleepiness over a seven-year period. This suggests that daytime fatigue may be a valuable warning sign for future ­dementia risk.

Additionally, elderly people with sleep issues and reduced oxygen while they sleep have more tiny strokes (microinfarcts) and greater brain cell loss than those who sleep well, and they may be at higher risk for cognitive decline.

Regular sleep disturbance is not a normal part of aging. People who experience chronic sleep problems (see “Sleep Problems Matter”) or who have conditions such as sleep apnea or restless legs syndrome should seek treatment. New research suggests that even short-term sleep deprivation can have harmful consequences at the cellular level in our brains.

But don’t necessarily turn to prescription medications to improve your sleep. Sleep experts recommend instead making good sleep hygiene—a pattern of habits and behaviors conducive to quality sleep—a priority, and a part of your regular routine.

To achieve good sleep hygiene, get a better night’s sleep, and bolster your memory, experts recommend that you:

• Try to go to bed at the same time each night and awaken at the same time each morning.
• Sleep in a darkened room with minimal noise.
• Do something relaxing before bed, like reading a book or taking a bath.
• Seek treatment for anxiety, medical conditions, and mood disorders that may interfere with your sleep.
• Eat small meals in the evening.
• Limit alcohol and avoid caffeine at least four to six hours before you go to bed. Stop drinking liquids close to bedtime to avoid middle-of-the-night bathroom visits.
• Speak with your doctor about medications you are taking that may be interfering with your sleep.
• Get plenty of exercise to help reduce tension and promote relaxation, but don’t exercise too close to bedtime.
• Get outside in the sunlight for at least 10 minutes each day.

Seek Social Engagement

Having close relationships and staying socially active may help keep your memory strong and slow cognitive decline. Social interaction requires paying attention to your surroundings, following a conversation, responding to the actions of others, and watching for verbal and non-verbal cues, all of which require a lot of brainpower. People who describe themselves as feeling lonely and socially isolated are twice as likely to develop dementia as people who report being socially active. Socializing delivers many benefits, including mental stimulation, reassurance and support, a reduced likelihood of depression, and an improved quality of life.

To keep your memory sharp, get out with friends as often as you can, even if it’s just for a quick dinner. Calling, emailing, or Skyping with friends and loved ones also can keep you socially active.

If you’re socially isolated, make an effort to engage with others, whether it be neighbors or colleagues or people you meet in a community class or activity. Volunteering can be a great way to meet new people while engaging your mind in a meaningful activity. Push yourself to find opportunities to interact with others. Research shows it may not only improve your mental acuity but also your mental well-being.

Move Your Mental Muscle

Mounting evidence suggests that exercising your brain with stimulating and challenging activities, such as reading the newspaper, playing checkers, working in an intellectually stimulating job, or going to a play may keep it sharp and help prevent dementia.

Activities that require concentration, use many senses at once, and involve new or unexpected experiences and approaches may help to create a buffer against cognitive decline, which doctors call cognitive reserve. Researchers have found that people with more cognitive reserve are better able to withstand the degenerative brain changes associated with AD and other forms of dementia.

Scientists are starting to tease out precisely how stimulation may change the brain in ways that lead to better memory performance and lower risk for AD. One study suggests that staying mentally active in middle age can reduce levels of beta-amyloid protein in the brains of people with the ApoE4 gene variation and slow the onset of Alzheimer’s symptoms. Brain-stimulating activities might make the brain fitter and more efficient. And, since the production of toxic beta-amyloid is linked to brain inactivity, a more efficient brain would be likely to produce less beta-amyloid.

Other research suggests that mental activity may reshape the brain through the promotion of powerful growth hormones. Learning stimulates the release of a protein called brain-derived neurotrophic factor, which helps keep brain cells functioning optimally and promotes the development of communication points between neurons, called synapses.

Challenge your mind with crossword puzzles, brain teasers, math problems, or sudoku puzzles. Learn a favorite poem by heart, memorize the capitals of all 50 states, or commit your shopping list to memory. Play card games—alone or with friends—or challenge family members to a game of Scrabble, chess, bridge, or poker. Read newspapers and magazines to keep up with current events and keep a journal. Try new hobbies, take dance lessons or a class at a local college, or learn a new language. Go back to work part-time at a mentally stimulating job that allows you to engage with your co-workers. Even changing your daily routine from time to time can be mentally stimulating.

Your Brain and Injury

Several studies show that a head injury may increase the risk for dementia and for developing cognitive loss earlier in life. In recent years there have been a wave of news reports focusing on football players who were diagnosed with chronic traumatic encephalopathy (CTE), a progressive brain disorder marked by the buildup of tau protein—the same protein found in the brains of people with Alzheimer’s.

A recent study from Boston University discovered CTE in 99 percent of the brains of former football players they studied. This finding has led the medical community to focus on the risks of brain injuries, and on efforts to prevent them.

Traumatic brain injury (TBI), caused by a blow to the head, a fall, or even violent jarring, may injure sensitive brain tissues in ways that might cause later declines in cognition. TBI leads to 2.8 million emergency department visits, hospitalizations, and deaths each year. Falls are the No. 1 cause of these injuries (47 percent). Symptoms of TBI vary depending on the area of the brain affected by the injury, and may not show up until hours, days, or even weeks later (see “Symptoms of Traumatic Brain Injury”). Prompt medical treatment may help prevent further damage.

Although more research is needed to clarify the relationship between TBI and dementia, taking steps to protect yourself from head injury is a wise precaution. Some common-sense suggestions:

• Use your seatbelt when you drive or ride in a car.
• Check your home for fall hazards, such as loose rugs or electrical cords, and eliminate them.
• Wear appropriate footwear, such as non-slip boots in icy weather.
• Have your doctor recommend exercises that can improve your muscle strength, gait, and balance.
• Wear a helmet to protect your head while riding a bike or engaging in other activities that carry a risk of head injury.
• Check with your doctor to see if you can change medications to reduce the risk of falls; many drugs also lead to confusion, drowsiness, or cognitive changes.

It might seem daunting to read the many ways in which lifestyle choices can impact your risk for dementia, and making changes to your own lifestyle may seem even more so. However, it’s worth considering ways in which you might get “more bang for your buck.” For example, try combining strategies: invite a group of friends to sign up for a bridge class with you, ask a work colleague to consider taking a daily walk with you during the lunch hour, or ask a family member to join you in a healthy cooking class.

There are many ways in which you can tackle more than one lifestyle change—healthy eating, weight loss, exercise, socialization, and mental engagement—simultaneously, but it may help to start slowly. You likely won’t revamp all of your lifestyle risk factors in one month. The good news is that many of these changes can build upon one another. Eating a healthier diet may give you more energy for exercise; getting regular physical activity may improve the quality of your sleep and reduce your stress; learning a new skill with a group of friends might help you stick to your commitment, and so on and so forth.

The post 8. Helping Yourself appeared first on University Health News.

AD drug research is not for the faint of heart. The failure rate has exceeded 99 percent. Yet, despite this, each drug trial adds valuable information to our growing understanding of the disease, helping to inform future studies. The sheer number of studies continues to increase as well.

In 2019, there were more studies in every phase than there had been in 2018, and the scope of studies is expanding.

Researchers are evaluating new biomarkers, developing new and more advanced outcome measures and enrolling patients in earlier stages of the disease process. Experts anticipate improvement in drug development success rates in the coming years as new drugs move through phase 2 and 3—often called the “learn” and “confirm” trials—in which they see if benefit can be achieved (phase 2) and then confirm it in larger-scale, longer-term trials (phase 3).

Drugs in the Pipeline

When thinking about the various drugs in the AD research “pipeline,” it can be helpful to think about the way researchers are anticipating those drugs might impact the disease:

1. Modifying the underlying disease pathology,
2. Improving existing cognitive symptoms, and
3. Addressing neuropsychiatric symptoms.

The first category is the only one that, in theory, would truly change the course of the disease while the latter two would help slow progression or mitigate symptomatology. And, while the majority of studies currently underway are looking at the first category, at this point in our understanding of the disease, all three categories have considerable merit and are the subject of active research.

Drugs that target amyloids continue to dominate the research field, but with repeated failures of anti-amyloid drugs and discovery of new processes involved in the disease progression, this trend is changing. Anti-amyloid drugs represent the greatest proportion of phase 3 disease modifying studies, but this is not the case for phase 2 studies—perhaps indicating a shift in research direction.

Targeting Beta-Amyloid

Beta-amyloid is the target of roughly 35 percent of the drugs that are currently undergoing phase 3 trials, which is a decrease from previous years. Scientists are focusing on preventing the production of the pathologic forms of beta-amyloid or removing the pre-existing abnormal protein from the brain.

One of the primary anti-production strategies has focused on blocking enzymes that may influence the development of AD, in particular the enzyme—BACE—that cleaves amyloid precursor protein (APP) into beta-amyloid. Unfortunately, one of the most anticipated drugs in this category, CNP520 (umibecestat) recently failed. The hope was that by inhibiting this enzyme, the cascade of events leading to the formation of amyloid plaques could be disrupted. However, in an interim analysis of a randomized, double-blind, placebo-controlled trial of almost 2,000 participants, those patients randomized to the drug showed signs of worsening cognitive function causing the investigators to discontinue the study.

Another BACE inhibitor, however, is showing more promise. E2609 (elenbecestat) has been shown to be safe and effective in phase 1 and 2 studies and is currently being investigated in a multi-site phase 3 study comparing 50 mg of the drug to placebo in adults with early AD. The study will measure cognitive function outcomes as well as other functional outcomes and safety measures, and is expected to conclude in 2023.

Recently, the Alzheimer’s Clinical Trials Consortium (ACTC)—a network funded by the NIA and directed by researchers from the Keck School of Medicine of USC, the Mayo Clinic College of Medicine and Science, and Harvard Medical School—recently selected elenbecestat to be evaluated in two large multi-site clinical studies set to begin this year.

The first study, called the A3 study, will assess whether elenbecestat can prevent amyloid buildup in the brains of cognitively normal individuals whose brain amyloid levels are below the threshold for elevated amyloid but who are at risk for further accumulation.

The second study, the A45 study, will target individuals in the preclinical stages of AD (no/minor cognitive impairment, elevated brain amyloid). Subjects will be treated first with a drug, BAN2401, which is an antibody to beta-amyloid designed to clear antibody deposits in the brain, and then with elenbecestat to reduce amyloid production and prevent reaccumulation. BAN2401 is also under investigation in a separate phase 3 study of patients with MCI or early AD with results expected in 2024.

Positive news has come from the study of another drug aimed at preventing amyloid plaque formation, tamiprosate. Tamiprosate is thought to work by enveloping amyloid peptides and preventing the transformation pathway that leads them to form oligomers and then ultimately plaques. In a study reported in The Journal of the Prevention of Alzheimer’s Disease in 2016, tamiprosate significantly improved cognition and function in individuals carrying two copies of ApoE4: a variant of the apolipoprotein E (ApoE) gene that is associated with a greater risk for AD.

Scientists then tweaked the drug, developing a pro-drug form of tamiprosate—ALZ-801—that has fewer side effects than tamiprosate and better pharmacokinetics. The U.S. Food & Drug Administration granted “fast-track” status for ALZ-801 based on its preliminary study results and safety profile.

A study evaluating ALZ-801 in individuals with mild AD and two copies of ApoE4 found that patients taking the drug had better preservation of cognitive function than those taking placebo. The company that manufactures ALZ-801 is planning to study the drug in other populations of AD patients.

Immunotherapy and Vaccines

One of the most exciting and best-­studied group of new therapies for Alzheimer’s disease harnesses the body’s own immune system, using vaccines or antibodies to find and destroy beta-amyloid and clear out plaques in the brain, or eliminate the clumps of tau protein that kill neurons and thus lead to memory loss. Two types of immunotherapy are under investigation:

• Active immunotherapies induce a response from the patient’s own immune system.
• Passive immunotherapies administer antibodies to create an immune response.

Scientists are studying both active and passive immunotherapies targeting the accumulation of beta-amyloid proteins. A few active therapies have produced antibody responses to beta-amyloid, including the CAD106 vaccine.

The Alzheimer’s Prevention Initiative Generation Study launched in August 2016 to study whether the CAD106 vaccine might stop amyloid buildup and prevent or delay Alzheimer’s symptoms.

The study initially looked to assess the efficacy of the BACE inhibitor, CNP520, in one arm and the CAD106 vaccine in a separate arm; however, the CNP520 arm was discontinued in 2019 because of worsening cognitive function. The CAD106 study arm, which includes adults ages 60 to 75, who have normal memory and thinking ability, but are at high risk for AD because they carry two copies of the ApoE4 allele, will run through 2025.

In 2016, researchers at Flinders University in Adelaide, Australia, announced the development of a combination vaccine platform called MultiTEP that causes the immune system to produce antibodies against both beta-amyloid and tau proteins. Studies in animals show that the vaccine is effective, and the researchers hope to test the vaccine in human trials within the next few years.

Passive immunotherapy research focuses on drugs called monoclonal antibodies. These drugs, which are already used to treat cancer, are engineered in the laboratory to mimic the antibodies the immune system naturally produces when confronted by bacteria, viruses, and other foreign invaders.

In the case of AD, monoclonal antibody drugs are engineered to target and destroy beta-amyloid proteins. So far, a few experimental drugs, including solanezumab and gantenerumab, have had disappointing clinical trial results in people with AD.

In early 2019, the manufacturer of another antibody drug, crenezumab, halted two large phase 3 studies because an interim data analysis indicated the drug was unlikely to achieve its outcome of cognitive improvement. A similar fate befell studies of the beta-­amyloid antibody drug, aducanumab, just months after the crenezumab studies were ended.

Researchers are learning that early intervention may be the key to stopping these destructive plaques, so they are trying a different approach with anti-amyloid drugs. For the first time, they are administering monoclonal antibodies before Alzheimer’s takes root.

To that end, Reisa Sperling, MD, of Brigham and Women’s Hospital, is leading a landmark research effort called the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Study (the A4 Study). This multimillion-dollar effort will include 1,000 adults with normal mental function but high levels of amyloid plaque in their brain. A4 will test whether solanezumab can clear these beta-amyloid deposits, along with tau buildup, thereby preventing cognitive decline. The study is expected to conclude in December 2020.

“The A4 study is the first trial designed to prevent memory loss, by identifying individuals who have the earliest changes of AD in the brain, but don’t yet have evidence of any symptoms,” Dr. Sperling says. “This trial will test a specific investigational treatment that’s designed to help the brain clear amyloid.”

Some of the most exciting data from a passive immunotherapy treatment strategy to date has come from the amyloid-targeting drug, BAN2401 (see “Targeting Beta-Amyloid,”on the previous page). Although early interim results were disappointing, data analysis of this antibody to beta-amyloid at the 18-month mark were far more promising in patients with early stage Alzheimer’s and the drug is being investigated in two phase 3 studies.

Immunotherapy also is being investigated to focus on abnormal tau proteins. A vaccine called AADvac1 has been studied in several phase 1 trials and was found to be safe and to elicit antibodies against the abnormal tau protein. A two-year phase 2 trial, completed in 2019, looked at the vaccine’s safety profile, along with cognitive performance and antibody production, in 208 participants with mild Alzheimer’s, but results have not yet been reported.

Passive immunotherapy using an anti-tau antibody called RO7105705 is being studied in a phase 2 study of 360 individuals between the ages of 50 and 80 with early stage Alzheimer’s. Participants will be randomized to the antibody or placebo and will be monitored with tau PET scans and serial cognitive assessments. The trial is set to run through 2022.

A second phase 2 study of RO715705 was initiated in 2019 in individuals with documented amyloid positivity (either by PET or CSF) and moderate dementia. Another anti-tau antibody, ABBV-8E12, is also being evaluated in a phase 2 study of 400 individuals with early AD and is estimated to finish in 2021.

Targeting Tau

In addition to the immunotherapy strategies targeted toward tau, researchers have begun to focus on other ways to inhibit abnormal tau protein. These drugs, however, represent a minute fraction of those in the pipeline, particularly among those that are in phase 3 trials.

Although research into tau-targeted drugs lags far behind beta-amyloid-based treatments, several drugs are currently under investigation. One such drug is leuco-methylthioninium (LMTX), which is thought to dissolve existing tau in the brain and prevent additional tau from forming.

A study presented at the 2016 Alzheimer’s Association International Conference found LMTX didn’t improve cognition or function in people with AD. However, despite the disappointing results, further studies, including a phase 3 study of 800 patients with mild disease, have shown that when given as a single drug therapy, LMTX might significantly slow the rate of brain atrophy. A phase 2/3 study of two different doses of LMTX and a placebo in 375 individuals with AD is currently underway with primary outcomes being FDG PET scans and cognitive function.

In early 2017, researchers at Washington University in St. Louis announced they were able to prevent Alzheimer’s-related brain damage by blocking tau production in monkeys and mice. They used compounds called antisense oligonucleotides (ASOs)—short sequences of DNA or RNA that have been genetically engineered to shut off tau production genes. The first phase 1 study of an anti-tau ASO, BIIB080, is underway in 44 adults with mild AD in Canada and Europe.

Another drug, ANAVEX2-73, targets not only tau but amyloid and inflammation as well. It is thought to improve cell signaling, reduce amyloid levels, and diminish tau phosphorylation. Phase 1 and 2 studies demonstrated the drug had a good safety profile. The phase 2 study also demonstrated improved mood and alertness and better social engagement among study participants. The study was extended at the request of family members and is set to conclude in 2020. Meanwhile, a phase 3 study evaluating two different doses of the drug vs. placebo in individuals with AD is expected to wrap up in 2021.

Histone Deacetylase Inhibitors

Drugs called histone deacetylase (HDAC) inhibitors offer new promise in fighting age-related memory decline and AD. HDACs are a group of 11 enzymes that control which genes are expressed and able to produce their respective proteins. This function can have important implications. For example, if a gene that triggers cell death (apoptosis) is silenced, it can lead to uncontrolled cell growth and ultimately to the formation of a cancerous tumor. This is why HDAC inhibitors were first developed—to treat cancer. But these drugs also may be useful for neurodegenerative diseases like AD.

One HDAC in particular, HDAC2, silences genes that are needed to form new memories. It is overproduced in the brains of people with AD. When researchers at MIT shut off this gene in the hippocampi of mice with AD, it restored normal cognitive function. Another study, this one of an HDAC6 inhibitor, found that it reduced brain tau levels and restored memory in mice with AD. Human studies are now looking at HDAC inhibitors. In a phase 2 study currently underway, scientists from the University of California, Irvine, are looking at whether nicotinamide (vitamin B3), an inhibitor of a class of HDAC, will reduce levels of tau in the CSF of individuals with MCI or mild AD.

Insulin

Insulin is a hormone that helps the body use sugar from foods as energy. Research is finding that this hormone might also have strong links to AD. The same enzyme breaks down both insulin and beta-amyloid. A disruption in insulin signaling in the brain can affect amyloid removal, cell survival, inflammation control, blood vessel function, and other factors involved in the development of AD.

Researchers are investigating whether an insulin nasal spray might help with Alzheimer’s and other forms of dementia. Delivered this way, insulin would bypass the bloodstream and therefore not cause unwanted side effects such as hypoglycemia (low blood sugar) or insulin resistance. A long-acting form of insulin called detemir (Levemir) appears to improve working memory (the ability to process and retain new information) in people with mild cognitive impairment (MCI) or early-onset AD who also have the ApoE4 gene. More research is needed to find out why the treatment is most effective in people with the ApoE4 gene, and to confirm the safety and effectiveness of an insulin spray for treating early Alzheimer’s.

In another study, researchers looked at whether a short-acting intranasal insulin impacted cognitive function in individuals with amnestic MCI (see Chapter 2) or early stage Alzheimer’s. The multicenter study, called the Study of Nasal Insulin in the Fight Against Forgetfulness or SNIFF study, randomized 240 individuals to twice daily doses of intranasal insulin or placebo and followed them for 12 months with cognitive assessments, MRI, and biomarker profile. The study was complicated by difficulty with the initial intranasal insulin device.

After the first 49 study participants started the study, the researchers switched to a different device (device 2) for the other study participants. Interestingly, at the end of the 12 months, they found no difference in outcomes between the placebo and device 2 patients, but they did see a trend toward improvement in the original device (device 1) group. Participants were given the opportunity to continue the study for another 6 months, all receiving intranasal insulin, with the same monitoring.

At the 2019 AAIC, the study authors reported that participants who had used device 1 had better cognitive and daily life activity test scores than did the patients originally receiving placebo. They also had significantly improved biomarker profiles. While the number of individuals in the device 1 group was small, the researchers suggest these results hold real promise as they occurred in individuals already suffering from AD symptoms. Larger studies will be needed to demonstrate that these results can be repeated.

Other Targets

As of 2019, 132 drugs were in the AD pipeline, up from 112 in 2018. Nearly 30 of these drugs had reached phase 3 trials, which test safety and effectiveness in large groups of patients. Researchers hope that some of the drugs being evaluated will either improve cognitive symptoms or improve neuro­psychiatric symptoms such as agitation or insomnia.

Here are just a few of the therapies under investigation:

Guanfacine. British researchers are investigating whether this drug, used to treat Attention Deficit Hyperactivity Disorder in children, will improve thinking and attention in patients with AD who are taking a cholinesterase inhibitor. Guanfacine boosts the levels of the neurotransmitter norepinephrine, which is reduced in AD. The phase 3 study has enrolled 160 participants and is scheduled to be complete in 2021.

Escitalopram. Also known as Lexapro, this drug is a selective serotonin reuptake inhibitor commonly used for depression. In a phase 3 study funded by the NIA, researchers are looking at whether escitalopram reduces agitation in patients with AD. Study participants will be randomized to the drug or placebo and followed for 12 weeks with clinical assessment every three weeks and phone call assessments in between. After the first 12 weeks, the drug will be discontinued, and all patients will be followed for an additional 12 weeks. The trial is set to end in 2022.

Nabilone. Results of a phase 3 study of a synthetic cannabinoid for the treatment of AD-associated agitation were presented at the 2019 AAIC. The researchers found that nabilone significantly improved both agitation and overall behavioral symptoms compared to placebo in the study participants, though they caution that there was an association with increased sedation.

More Promising Findings

SAK3. Researchers in Japan developed a drug called SAK3, which stimulates the release of the neurotransmitter acetylcholine in the brain. Acetylcholine plays an important role in both attention and cognition, and its dysfunction has been linked to both Alzheimer’s and vascular dementia. The authors say the drug  improves cognition, and inhibits amyloid accumulation, and demonstrates a good safety profile in animal trials. They expect clinical trials in humans to start within a few years.

Riluzole (Rilutek), a drug that affects the neurotransmitter glutamate and has been used to treat amyotrophic lateral sclerosis (ALS) since the 1990s, is undergoing a phase 2 study as an adjunct to individuals with mild Alzheimer’s who are already taking the cholinesterase inhibitor, donepezil (Aricept). The trial is expected to conclude this year.

ALZT-OP1. Neuroinflammation has been shown to be a key factor in the degeneration of brain cells in AD. ALZT-OP1 is a drug that combines the anti-inflammatory drug, ibuprofen, with cromolyn, which is a mast cell stabilizer used to treat asthma. Cromolyn works by decreasing the release of inflammatory chemicals called cytokines that are thought to contribute to the inflammatory processes in AD. ALZT-OP1 is being studied in a phase 3 study, called COGNITE, which will have four arms and enroll 600 participants with early AD. The study is anticipated to conclude late this year.

AGB101. Research shows that neuronal hyperactivity drives both amyloid and tau pathology in the brains of people with AD. AGB101 is a drug designed to decrease that overactivity and hopefully improve cognitive function. A phase 2 study demonstrated that the drug reduced hyperactivity in the brains of study participants and improved episodic memory, which is the earliest memory deficit seen in MCI. An NIA-funded phase 3 study, called the HOPE4MCI study, is evaluating AGB101 in over 800 people with MCI due to AD.

Calcineurin Inhibitors. People with AD have high levels of an enzyme called calcineurin, which plays a role in the harmful effects of beta-amyloid on the brain. Researchers at the University of Texas showed that blocking this enzyme restored memory in mice. They also discovered that people who receive calcineurin inhibitor medicines such as tacrolimus (Protopic) or cyclosporine (Gengraf) after an organ transplant are significantly less likely to develop dementia. The researchers plan to test calcineurin inhibitors in human trials, to see if they might prevent AD development.

PXT-864. This mixture of acamprosate calcium (used to treat alcohol dependency) and baclofen (a muscle relaxer) is being studied to treat AD, Parkinson’s, and ALS. The drug combination is thought to work synergistically to calm hyperexcitability in the brains of people with AD. Results from phase 2 studies of PXT864 are promising, showing cognitive stabilization in patients with mild AD.

Focused Ultrasound. One challenge in delivering Alzheimer’s drugs has been getting past the blood-brain barrier. In 2017, a team from Toronto tested a technology called focused ultrasound to open this barrier in a small group of Alzheimer’s patients. Clinical trials evaluating the safety and efficacy of the technology are underway in the U.S., Canada, and France. Once the ultrasound technology is proven safe and effective, researchers plan to use it to introduce an anti-amyloid drug directly into the brain.

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While this research is underway, past research has helped advance available treatments to the point where they can help manage some of the most troubling cognitive and behavioral symptoms, and make life easier for people with the condition, and their caregivers.

Planning

Progressive decline with AD is inevitable, making planning a critical part of the treatment paradigm. When a ­diagnosis is made, the patient, their ­primary caregiver(s), and the health-care provider must work together to ­discuss the patient’s wishes, educating the caregiver(s) on the typical disease progression, evaluating living arrangement options, and discussing treatments.

Alzheimer’s Medications

Some experts believe that the first step in pharmacologic management of Alzheimer’s is a re-evaluation of a patient’s existing medications. Many medications are contraindicated or not recommended for people with AD. For example, diphenhydramine (Benadryl) is commonly taken with acetaminophen for pain or sleep relief, yet its use is discouraged in patients with AD because it is an anticholinergic.

Benzodiazepines, often taken for anxiety or insomnia, and benzodiazepine-related drugs—zolpidem (Ambien), eszopiclone (Lunesta), and zaleplon (Sonata)—that are used as sleep aids should also be avoided. In addition, benzodiazepines are associated with an increased risk of mortality—as high as 40 percent—in patients with AD.

These medications are associated with a dose-dependent increased risk of fractures in patients with AD. Reviewing what is in the medicine cabinet of a patient with dementia and eliminating drugs that pose a risk is therefore an important part of AD management.

When it comes to drugs used to treat Alzheimer’s, there are two primary categories: 1) those that treat memory, language skills, and other cognitive symptoms of the disease and 2) those that address agitation and other behavioral issues.

Treating Cognitive Symptoms

Four drugs are approved to treat the cognitive symptoms in Alzheimer’s. Three are cholinesterase inhibitors and one is an N-methyl-D-aspartate (NMDA) receptor antagonist.

Cholinesterase Inhibitors. The multiple factors that appear to play a role in Alzheimer’s result in a progressive loss of neurons. To date, there are no approved medications that can prevent that cell death. Cholinesterase inhibitors, however, boost the function of the remaining cells by increasing levels of an essential brain chemical—the neurotransmitter acetylcholine. By inhibiting the enzyme that breaks down acetylcholine, this class of drugs has been shown to modestly improve memory and other cognitive function, along with daily functioning, in some people with mild-to-moderate Alzheimer’s. Unfortunately, these results vary among individuals and in those who do see benefit, it is typically only for a ­couple of years.

Of note, the drugs in this class appear to be about equally effective at improving cognition and the ability to function in people with mild-to-moderate AD. Only one cholinesterase inhibitor, donepezil (Aricept), is approved for use in severe AD. Common side effects of cholinesterase inhibitors include nausea, diarrhea and fecal urgency, and vivid or disturbing dreams.

Three cholinesterase inhibitors are approved by the U.S. Food & Drug Administration (FDA) to treat people with AD:

• Donepezil (Aricept) is suitable for people with mild-to-severe Alzheimer’s. When taken once a day, it can help with memory and other daily tasks.
• Rivastigmine (Exelon) is for mild-to-moderate Alzheimer’s. It can be taken twice daily by mouth or applied once a day in patch form. The patch is associated with fewer gastrointestinal side effects than the oral form, and it can help patients who have trouble swallowing. The patch also is approved to treat dementia related to Parkinson’s disease.
• Galantamine (Razadyne), used in mild-to-moderate Alzheimer’s, improves mental function and behavior in patients with Alzheimer’s, as well as in those with both Alzheimer’s and vascular dementia. An extended-release version can be taken once a day.

NMDA Receptor Antagonist. The only NMDA receptor agonist is memantine (Namenda), which treats moderate-to-severe AD. Memantine works by regulating the action of a chemical messenger in the brain called glutamate, which, in excess, can damage nerve cells.

When used alone or with donepezil (and other cholinesterase inhibitors), memantine can modestly improve cognitive function and the ability to perform daily activities in some patients. When used together, the two drugs delay nursing-home placement for patients with AD. The most common side effects from the medication are constipation, drowsiness, dizziness, and headache.

Treating Behavioral Symptoms

Behavioral and psychiatric symptoms are arguably among the most challenging aspects of the disease, affecting as many as 85 to 90 percent of patients with dementia. They can be particularly distressing to caregivers. Symptoms such as anxiety, agitation, hallucinations, delusions, aggression, hostility, and uncooperativeness are among the biggest reasons why people with Alzheimer’s are institutionalized.

Although many doctors write prescriptions for drugs such as antidepressants to address behavioral symptoms, in many cases, non-drug approaches are as or more effective. Doctors recommend different non-drug strategies for coping with these behaviors before trying medication treatments (unless the person poses a safety risk):

• Educating the caregiver: It is critical to educate caregivers that changes in behavior and personality are because of the disease and not willful actions or personal affronts.
• Improving communication between the caregiver and the person with dementia: The Alzheimer’s Association advises caregivers to ask questions about personal comfort to see if physical symptoms might be the source of agitation. They also recommend avoiding confrontation or arguing over facts.
• Offering meaningful activities to the person with dementia: Activities that bring joy or calm to a patient may improve  their mood and behavior.
• Establishing routines with simplified activities: Simplified routines may help reduce anxiety and frustration.
• Creating a safe environment: In addition to avoiding situations in which a patient with dementia might get lost or disoriented, it is important to keep them in an environment that minimizes stressors, including elements such as excessive noise or glaring lights.

Other ways to improve the situation without drugs include addressing the causes of distress, distracting or redirecting the person, creating a peaceful environment that separates the individual from what seems to be upsetting them, and helping them engage in regular physical activity to potentially reduce irritability and aggressive behavior. Addressing potential medical causes of agitation or negative behaviors is critical.

Side effects from medications used for AD, deterioration in vision or hearing, constipation, and indolent infection (such as an undiagnosed bladder infection) are among many factors that can cause new agitation and anxiety or exacerbate existing cases in someone with Alzheimer’s. Obtaining a thorough medical evaluation should be one of the first steps in evaluating these kinds of behavioral symptoms.

If these interventions don’t help, caregivers can speak to the patient’s doctor about medications to treat behavioral and psychiatric symptoms of Alzheimer’s. Although no drug is FDA-approved for this purpose, antidepressant medications may be used off-label. In rare, specific circumstances, antipsychotics can be used off-label.

Antidepressants. Antidepressants known as selective serotonin reuptake inhibitors (SSRIs) are used to manage symptoms of depression, and they can ease irritability and depression in people with Alzheimer’s. Examples of antidepressants used to treat behavioral symptoms of Alzheimer’s include:

• Citalopram (Celexa)
• Escitalopram (Lexapro)
• Fluoxetine (Prozac)
• Paroxetine (Paxil)
• Sertraline (Zoloft)

These medications may contribute to memory loss. However, older adults with dementia and symptoms of depression may see their cognition improve to some extent when treated with antidepressants.

In general, experts recommend starting slowly with these medications. Target one symptom, as relieving that symptom may alleviate other problems (e.g., treating depression may mitigate sleep problems). Also, start with the lowest dose possible to avoid any potential medication side effects.

Antipsychotic Medications. Among the most disturbing features of dementia are severe emotional symptoms, such as aggression, hostility, agitation, hallucinations, and delusions. These symptoms are so distressing that doctors may prescribe antipsychotic medications to alleviate them.

Examples of antipsychotic medications include:

• Aripiprazole (Abilify)
• Haloperidol (Haldol)
• Olanzapine (Zyprexa)
• Quetiapine (Seroquel)
• Risperidone (Risperdal)
• Ziprasidone (Geodon)

Some studies have questioned the value and safety of antipsychotic use in people with dementia. The FDA issued a “black box” warning on certain classes of antipsychotics in 2002 and extended it to all antipsychotics in 2008.

Guidelines from the American Psychiatric Association urge doctors to use antipsychotics in dementia patients as a last resort—only when symptoms are severe, dangerous, or cause the patient significant distress. Doctors should start their patients at the minimum dose and gradually increase it, keeping the minimum dose necessary. Patients who don’t respond after four weeks should be tapered off the drug. Even those who do show a response should be weaned off the drugs after four months and  followed up to see if their symptoms return.

Instead of turning to antipsychotic medications at the first sign of agitation, Maurizio Fava, MD, Psychiatrist-in-Chief, Massachusetts General Hospital  Director, Division of Clinical Research of the MGH Research Institute, recommends approaching behavioral issues on a case-by-case basis and using a range of possible strategies that reflect the specific circumstances and characteristics of the person with dementia. Non-­pharmacological options for calming an agitated person include:

•  Avoiding potentially upsetting situations: Prevent agitation by anticipating and resolving factors—such as boredom, excessive stimulation, or pain—that tend to cause disruptive behaviors.
• Giving in, when appropriate: Allow certain behaviors, provided they don’t complicate caregiving or pose a risk to the person with dementia or others. For example, if the person wants to select his own wardrobe, let him—even if it results in odd clothing combinations, as long as it is appropriate to the weather.
• Responding flexibly: Allow for changes in routine and environment to help keep the person calm. For example, if the person hates broccoli, replace it with an equally healthy vegetable. If baths cause problems, see if they can be less frequent, or if changing the person administering the bath can reduce disruption.

“You can also seek advice from support groups to help you find safe ways to cope with disturbed behavior,” Dr. Fava advises. “But if these basic measures do not work to control agitation, don’t hesitate to seek professional help. A health-care provider may recommend alternatives to riskier antipsychotic drugs that have been shown to help soothe some agitated individuals, such as cholinesterase inhibitors used to treat dementia, antidepressants such as trazodone (Desyrel) and SSRIs, anti-epileptic medications such as divalproex (Depakote), and lithium. If your loved one is being treated with antipsychotics, share your concerns about the medication with his or her care provider.”

If severe behavioral problems, such as hallucinations, delusions or aggression, don’t respond to other therapies, it may be necessary to prescribe antipsychotic drugs in the short term until other, less risky strategies can be found.

“Despite serious concerns, a case still can be made for the use of antipsychotic medications under certain circumstances,” says Dr. Fava. “In certain patients, the medications can help reduce some of the worst behavioral symptoms of AD. This is important because unmanageable behavior often triggers a move from home care to a nursing home, where antipsychotics may be necessary to prevent an unstable patient from harming another resident.”

Alternative Treatments

The slow progress in identifying new drugs for AD treatment has led many to look to alternative treatment options, ranging from special diets to over-the-counter supplements to home therapies.

Unfortunately, using supplements has yet to yield robust scientific evidence in its favor, although there are reasons for considering them. Experts caution, though, that supplements not vetted by the FDA (for efficacy or for safety) may have serious interactions with prescription medications. Discuss any supplement use with a health-care provider.

Huperizine A

Huperizine A is derived from a Chinese moss and has been studied in a number of smaller trials for its potential use in AD because it shares some features with cholinesterase inhibitors. While early studies showed some promise, the largest study to date in the U.S. to evaluate the drug—the Alzheimer’s Disease Cooperative Study—showed no benefit over placebo.

Coenzyme Q10

Coenzyme Q10 (CoQ10) is an antioxidant the body makes naturally. It is essential for cellular energy production and controlling cell-damaging free radicals created as a byproduct of that energy production. A synthetic version of CoQ10, idebenone, has been tested for Alzheimer’s but has not shown a benefit.

The National Institutes of Health (NIH) says that CoQ10 is well tolerated, although side effects and medicine interactions are possible. Research on it is inconclusive as to its benefits.

Ginkgo Biloba

Ginkgo biloba is believed to have antioxidant and anti-inflammatory properties, and the supplement is used in Europe to treat Alzheimer’s. Some research has shown modest cognitive improvements in patients with early-stage AD. However, the largest study to date found that ginkgo biloba was no better than placebo at warding off or slowing the progression of AD and other dementias.

Curcumin

Curcumin is an herbal compound extracted from turmeric, a dried root powder often used in curry recipes. Curcumin has some anti-inflammatory properties and has been explored as a potential treatment for AD. Animal studies have shown that curcumin can potentially inhibit both amyloid and tau aggregation, though no human studies to date have shown any improvement in cognitive function. Researchers from the Veteran’s Administration are currently studying whether combining curcumin with yoga (both aerobic and non-­aerobic) may impact disease biomarkers and cognitive outcomes. Study results are expected to be released in 2020.

Resveratrol

Resveratrol, a compound found in grapes, berries, and red wine, has strong antioxidant and anti-inflammatory properties. Animal studies suggest it might slow brain aging or prevent dementia, and researchers are investigating whether it might be beneficial for warding off mental decline in humans.

In a 2015 study that tested a supplement containing the amount of resveratrol in roughly 1,000 bottles of wine, patients with mild-to-moderate AD showed stabilization of a beta-amyloid marker linked to disease progression. Similar results were seen in a 2017 study published by researchers from Georgetown University. They found that in patients with mild-to-moderate AD, resveratrol appeared to reduce both levels of beta-amyloid and inflammatory markers. Further study is needed to see if these changes in biomarkers correlate with changes in disease progression.

Omega-3 Fatty Acids

The polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) found in a variety of food sources, including fatty fish, flax, soy, walnuts, and certain vegetable oils help modulate the structure of nerve cell membranes and are important to gene expression in the central nervous system. Research has linked omega-3 fatty acids to a reduced risk for heart disease, stroke, and possibly dementia. It’s well known that DHA and EPA are essential for nerve health and that AD is strongly correlated with a decrease in omega-3 levels in the brain and peripheral tissues. Recently, neuroimaging studies revealed that people with high omega-3 levels may have greater cerebral blood flow.

In a 2017 Journal of Alzheimer’s Disease study, researchers used an imaging technique called single photon emission computed tomography (SPECT) to look at blood flow in the brains of 166 participants as they performed a series of mentally challenging tasks. They noted that those individuals with higher omega-3 levels also had greater blood flow to regions of the brain involved with learning, memory, and dementia.

Studies on omega-3 supplements have shown mixed results, and at this time there is not enough evidence to recommend them as a means to prevent or treat AD, though another phase 3 study evaluating an omega-3 fatty acid is currently underway in the U.S.

Occupational Therapy

A French study published in the Journal of Alzheimer’s Disease found that occupational therapy reduces behavioral issues, improves patients’ quality of life, and reduces the burden on caregivers, especially helpful in the early stages of the disease.

An occupational therapist can make the home environment safer and basic tasks easier to complete. For example:

• Removing potential dangers around the home, such as locking up chemicals and medications, securing loose rugs, and removing knobs on the stove.
• Installing deadbolt locks on doors to prevent wandering.
• Providing written, step-by-step directions for basic tasks like getting dressed or using the microwave.
• Teaching the caregiver to deal with mood changes and other behavioral issues.

Music Therapy

One of the simplest ways to mitigate the damaging effects of Alzheimer’s might be by listening to music. The regions of the brain that process music are among the last to be damaged by dementia. So even in the late stages of the disease, when patients can’t recognize their family and friends, they can still remember the lyrics to their favorite songs.

Music stimulates areas of the brain involved with memory and attention, and it triggers the release of dopamine, a neurotransmitter that boosts mood. Listening to music not only brings joy to people with dementia, but evidence suggests it may help them recall lost memories and cope with the stresses of their disease.

The first national study of music therapy on nursing home residents with dementia, which was published online April 2017, in the American Journal of Geriatric Psychiatry, found that listening to music improved patients’ behaviors, and reduced their reliance on antipsychotic and anti-anxiety medicines.

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The good news is that most memory lapses are not associated with dementia but are due to age-related changes in the brain, or physical or emotional causes, many of which are treatable. It is when these memory issues begin to happen more often, making it hard to recall once familiar information or perform sequential steps in a task, that mild cognitive impairment (MCI) may be to blame.

MCI describes a condition that is more severe than normal, age-related memory loss and can sometimes, but not always, precede dementia. Research shows that MCI is more likely to develop among people who begin to report some memory loss in their 70s compared with people who don’t notice memory loss. Yet the progression to MCI, if it happens, is generally a slow one, often taking several years to occur.

Treatable Conditions

As the brain ages, so does the body. Some of these physical changes in our overall health can also cause changes in our memory. These alterations in memory function are distinct from age-related or dementia-related brain changes in that they can be reversible. In many of these cases, treating the underlying condition also resolves the memory issues.

The list of medical conditions that can negatively impact your memory is a lengthy one. Conditions ranging from sleep deprivation, alcohol abuse, poor nutrition, thyroid disorders, liver and kidney problems, dehydration, low blood sugar, and head injuries to certain medication reactions can all be culprits when it comes to memory problems (see Chapter 3 for more on the causes of memory loss). Because not all of these conditions will have other symptoms as obvious as memory impairment, it is critical to consult your health-care provider if you are experiencing memory problems. He or she will perform a comprehensive evaluation, looking for all potential causes of memory impairment, including those that may be caused by treatable medical conditions.

The feelings and emotions we experience with different life events can also exert a profound impact on our memory. Emotional distress, especially, can have a devastating effect on memory. Anxiety, depression, and chronic stress can interfere with the normal encoding and storage process and can significantly affect our ability to remember even the ­simplest things.

The triggers for this emotional distress can be normal life events—the loss of a loved one, a move, or an “empty nest.” Coping with these events can lead to some temporary inattention, mild forgetfulness, or confusion in the aftermath for some people. While support from friends and family can ease some of the stress, should symptoms persist, it is imperative to seek help from a health-care provider. Help in the form of counseling, medication, or lifestyle changes can relieve some of the emotional distress and any associated ­memory impairment.

Age-Associated Memory Changes

If you have noticed that your ability to recall names or find the words you want to use to describe something has diminished with age, you are likely not alone. These changes can be a normal part of the aging process. Similarly, you might find that multi-tasking has become more challenging or that it takes more energy to focus your attention. For example, you may notice that to keep up with the plot of a novel, you need to read at a slightly slower pace than you used to or that it is a little more difficult to recall all the points made by a speaker you heard a few days ago.

These age-associated memory changes are thought to be the result of a number of physiologic changes that occur in our brains over time. One of the most notable changes is an actual shrinkage of the brain, resulting from a loss of brain weight and volume at a rate of about 5 percent per decade after age 40.

If you’ve ever seen an image of a human brain, you’ll recall the surface being composed of a maze of wrinkles or folds (called gyri) with spaces (called sulci) in between. As we age and our brain shrinks, these gyri become smaller and the sulci widen.

Similarly, the large spaces inside our brain that contain cerebrospinal fluid—called ventricles—begin to increase in volume. Imaging studies show that this shrinkage doesn’t tend to occur uniformly throughout the brain; but instead, it is more pronounced in some areas, like the prefrontal cortex, that are responsible for more complex mental activities like executive functioning, which is the ability to plan, organize, and complete a task or tasks.

All of this is largely due to two factors. The first is that, as we age, we start to lose brain cells (neurons), a few at a time, although people who remain healthy and are mentally, socially, and physically active are able to generate new cells to replace many of these lost neurons. At the same time damage from aging occurs to the branch-like dendrites and nerve fibers, called axons, that extend from one neuron to another.

Additionally, blood flow to the brain decreases with age, as do levels of certain hormones and neurotransmitters that are involved in the transmission of signals among cells in the brain, and to and from the brain and other parts of the body. Some evidence suggests that the neurotransmitter dopamine, which plays a role in both cognitive and motor performance, begins to decline at a rate of 10 percent per decade beginning in early adulthood. The combination of fewer brain cells and lower levels of brain chemicals like hormones and neurotransmitters changes the way the brain stores new information and makes it harder to recall information already stored.

Among the factors that distinguish physiologic changes in age-associated memory decline from changes seen in Alzheimer’s disease (AD) is the type of matter most affected. Research suggests that in the normal aging process, changes in the brain’s “white matter”—the bundles of long, slender, sheathed nerve fibers that project from neurons and enable them to communicate with other neurons—are greater than those in the “gray matter”—areas in the brain’s cortex that are responsible for most important memory functions. By contrast, AD impacts the gray matter to a much greater extent than the white matter.

Finally, you may be surprised to learn that many of the hallmark features of AD—the formation of twisted protein filaments, called neurofibrillary tangles, inside nerve cells, as well as the buildup of clusters of damaged beta-amyloid proteins, called plaques, in the brain’s gray matter—can also be found in the brains of older people who show no signs of dementia. Why the presence of these markers is associated with dementia in some people but not in others remains a subject of ongoing research.

Cognitive Reserve

These age-related brain and memory changes do not occur for everyone. Researchers have found that some older individuals maintain razor-sharp memory function into their 80s and beyond. On a physiologic level, these individuals tend to have far fewer neurofibrillary tangles than most people and they appear to be resistant to the formation of the twisted filaments (although they still can develop plaques).

This resiliency to the ravages of age and conditions like AD is known as “cognitive reserve.” The concept first originated in the late 1980s, when researchers described 10 cases in which deceased individuals who had no apparent symptoms of dementia while they were alive showed signs of advanced AD in postmortem brain scans.

Since then, research has supported the concept that individuals can create a “buffer” of sorts that protects them from the cognitive deficits seen with age- or disease-related brain changes. This buffer is thought to be a result of a greater proliferation of and connection between neurons in the brain in response to cognitively stimulating experiences.

Factors like education, an intellectually challenging career, exercise, and mentally and socially stimulating activities are thought to contribute to cognitive reserve. Research suggests people with more cognitive reserve are better able to stave off the degenerative brain changes associated with dementia, or to maintain cognition in the face of those changes.

Noticeable Changes

Subtle declines in cognition, particularly among memory, reasoning, and vocabulary skills can start to appear as early as in your 40s. It is often not until the 50s, however, that people become more aware of an increase in memory lapses or other age-associated changes in cognitive skills. (see “Memory Through the Ages”).

It makes sense then that these changes tend to correlate with age. The older people are, the more difficulty they may have with working memory and mental organization. People may start to misplace things more easily, occasionally forget a name or phone number, have more trouble multitasking, become easily distracted, or struggle to learn things as easily as they once did. This phase is sometimes referred to as “subtle cognitive decline” or “subtle cognitive impairment.”

When MCI Appears

When the occasional memory lapse begins to become a regular occurrence but doesn’t impact your ability to continue living your life relatively unchanged, you may have crossed the line into mild cognitive impairment (MCI). MCI is the stage that comes after age-associated memory impairment, and it sometimes—but not always—leads to dementia (see Chapter 3). Currently, as many as 15 to 20 percent of Americans ages 65 and older have MCI, according to the Alzheimer’s Association. Although MCI is not the same as dementia, research suggests it may be a precursor to dementia, particularly Alzheimer’s.

According to Alzheimer’s Association statistics, as many as 32 percent of people with MCI may progress to dementia within five years. In a meta-analysis (a type of analysis in which the results of multiple studies are pooled and analyzed for a greater strength of evidence) of 41 studies, researchers found that among people with MCI who were followed for five years or longer, 38 percent ultimately developed dementia.

More recently, experts have begun to classify MCI into two different categories based on the skills that are affected.

• Nonamnestic MCI describes MCI affecting thinking skills other than memory including visual or spatial perception (e.g., finding it more difficult to navigate your way around a once familiar location), the ability to judge the steps needed to complete a complex task (e.g., pulling together your financial information to file your taxes), or language processing (e.g., losing your train of thought mid-conversation).
• Amnestic MCI refers to MCI characterized primarily by memory changes. People with amnestic MCI have more trouble remembering things that once came easily to them—like appointments or conversations. They also may begin to lose or misplace things more frequently. These memory problems are relatively mild, but people with MCI perform worse on cognitive tests than others of the same age group. Amnestic MCI is more likely to be caused by underlying Alzheimer’s disease and carries a greater risk of progressing to dementia. The National Institute on Aging reports that roughly eight out of every 10 individuals with amnestic MCI go on to develop dementia within seven years.

People with MCI still can perform their daily activities and have no apparent symptoms of dementia, although some complex tasks may require more effort or alternative strategies, such as greater use of lists, calendars, etc. People with MCI can live independently and take care of themselves—for example, they can get dressed by themselves, prepare their meals without assistance, eat their meals, and go on walks without getting lost. But in AD and other dementias, these functions gradually disappear.

To reduce the likelihood that you’ll develop MCI or that existing MCI will worsen, practice good lifestyle habits, like eating a nutritious diet, exercising, and managing health conditions that can impair brain function, such as high blood pressure, triglycerides, blood sugar, and LDL (“bad”) cholesterol levels, along with other risk factors.

If you believe you or a loved one may have MCI, consult a health-care provider who can help determine whether the memory impairment may be associated with a treatable physical or mental disorder. Being seen by a doctor can help ensure that you or your loved one gets optimal care and has access to new treatments for memory problems as soon as they become available.

Meanwhile, reduce daily frustration by adopting strategies to help with forgetfulness, such as making lists and keeping calendars of appointments. Whether or not you’ve been diagnosed with MCI, you still should plan ahead and make decisions regarding your future medical care and finances.

Serious Impairment

Most people who live into their 70s, 80s, and beyond never experience memory problems more severe than normal age-associated slips. But for some, forgetfulness may get progressively worse, and begin to interfere with everyday functioning.

Memory loss of any degree warrants an evaluation by a health-care provider. This is particularly true if you or a loved one has memory loss and it seems to be getting worse or is impacting your daily life. A medical assessment can help identify a cause and can help you create a course of action. Although there is no cure for AD, there are many steps you and your support network can take to address symptoms and plan ahead, and your health-care provider is a critical part of this process (see “First Alzheimer’s Disease Best Clinical Practice Guidelines Developed”).

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One of the prevailing theories for why researchers have yet to discover a drug that effectively treats AD is that these investigational drugs are being tested too late in the course of the disease. Many experts think that the cascade of brain damage that characterizes AD has progressed beyond the point of no return in patients enrolled in these trials and that research needs to focus on earlier stages of the disease—even preclinical stages—to see benefit.

But, here lies the rub: Diagnosing the disease before symptoms have occurred is extremely challenging. The most recent diagnostic guidelines from the National Institute on Aging (NIA) and the Alzheimer’s Association (AA) do not include diagnostic criteria for preclinical AD outside of the research setting, largely because many of the tests that allow for preclinical diagnosis are too new to have been standardized for widespread use. These guidelines may change sooner rather than later, however, as scientists continue to make significant strides in both validating and fine-tuning many of those tests.

In the meantime, our ability to diagnose AD in the early clinical stages has also improved dramatically. Studies have shed light on more subtle cognitive changes that herald AD, providing clues about early stages of the disease. Similarly, advances in neuroimaging technologies and the various structural changes that occur during the disease have aided early diagnosis.

Diagnostic Guidelines

Without a single, definitive diagnostic test for AD, experts from the NIA and AA have developed a multimodal approach for diagnosis in their diagnostic guidelines. The core components of these guidelines include a clinical history of cognitive decline, such as difficulty acquiring and remembering new information as well as trouble with complex tasks like making holiday meals or preparing tax records, and neurocognitive testing results that show clear deficits. Although it remains a supplemental component to diagnosis, biomarker testing—including imaging, blood, and cerebral spinal fluid tests—has become the subject of increasing focus as our understanding of the disease grows.

Knowing the Warning Signs

The symptoms of dementia can be subtle and because they often appear gradually, they can sometimes be easy to overlook. A partner, friend, or other relative may be the first to notice that something isn’t quite right. While most mild memory complaints are simply part of growing older, it is important not to ignore them. Watch out for these 10 warning signs from the Alzheimer’s Association checklist of common symptoms, and contact a doctor for assessment if you or a loved one experience:

• Recent memory loss that affects daily life
• Trouble planning or problem solving
• Difficulty performing familiar tasks
• Problems finding the right words when talking or writing
• Disorientation of time and place
• Trouble understanding visual relationships between objects
• Poor judgment
• Trouble finding things
• Lack of interest in going to work or participating in social activities.

Although memory loss has traditionally been one of the earliest AD symptoms, sometimes depression and behavioral changes like irritability and appetite loss emerge first. Researchers are trying to determine whether these symptoms are simply a reflection of the frustration brought on by early memory loss, or a direct result of Alzheimer’s damage to the brain.

Scientists at Brigham and Women’s Hospital found that challenges such as having trouble balancing a checkbook or driving to a doctor’s appointment correlate to dampened activity levels in certain parts of the brain. Detecting these difficulties early on, and understanding how they relate to changes in the brain, could ultimately pave the way for new treatments prescribed earlier in the course of the disease (see “Biological Definition of Alzheimer’s”).That’s why it’s important to be vigilant in watching for unusual cognitive symptoms beyond memory loss, and report them to your doctor.

Whether the changes are cognitive, behavioral, or functional, the U.S. Clinical Practice Guidelines, first announced at the 2018 Alzheimer’s Association International Conference, urge individuals concerned about changes in themselves or someone they know to seek medical evaluation. Studies show that early diagnosis allows an individual to be more involved in their future care and treatment plan, including participation in clinical research trials.

Diagnosing Alzheimer’s

For most individuals, an Alzheimer’s diagnosis will begin with a visit to your primary care provider. Your doctor will review your personal and family medical history, ask you about any symptoms you’ve experienced, review your medications, and give you a physical exam. He or she will likely administer a simple cognitive screening test, such as the Montreal Cognitive Assessment (MoCA) or Mini-Mental State Exam (MMSE), to look for formal evidence of cognitive decline.

You also may be referred to a neuropsychologist for tests that measure aspects of brain function such as memory, attention, executive functions (such as problem-solving abilities, calculation, and abstraction), language skills, and visuo-spatial abilities. Research reinforces the importance of cognitive testing in early disease detection.

Cognitive Function Tests

General diagnostic and cognitive function tests include:

General Practitioner Assessment of Cognition (GPCOG). This brief screening assessment incorporates both short-term recall and time/date orientation with a caregiver question list to highlight recent symptoms and changes in daily functioning. This test is typically used for the cognitive assessment that is now a part of the Medicare Annual Wellness visit.

Mini-Mental State Examination (MMSE). Your doctor will ask you a series of questions, such as the names of common objects, the date, the location of your doctor’s office, or to follow an instruction (see “The Mini-Mental State Examination”). The maximum score on the MMSE is 30 points. A score of 20 to 24 suggests mild dementia, 13 to 20 suggests moderate dementia, and less than 12 indicates severe dementia.

Montreal Cognitive Assessment Test (MoCA). The MoCA is a more sensitive test than the MMSE, especially for mild cognitive impairment (MCI) and mild or early-onset AD. Like the MMSE, it takes about 10 minutes to complete, and the maximum score is 30 points. MoCA is 100 percent sensitive at detecting mild AD, and 90 percent sensitive at detecting MCI.

Mini-Cog. This test asks you to remember the names of three common objects and then repeat them a few minutes later. You’ll also be asked to draw a clock showing a time your doctor specifies.

Computerized Tests. These tests offer an advantage over paper tests in that they are standardized, so they can be administered in exactly the same way each time they’re given. The U.S. Food & Drug Administration (FDA) has approved several computerized tests. These include CANTAB Mobile, a 10-minute memory test done using a touchscreen on a computer tablet or iPad; Cognivue, a computer-based test that creates a single brain health score; ANAM, a computer-based cognitive assessment program originally developed by the military for traumatic brain injury evaluation; and COGNIGRAM, another digital assessment tool that can be used on a one-time basis or for ongoing assessment.

Care Giver or Informant Testing. The 2011 diagnostic guidelines emphasized the importance of involving an “informant,” an individual who knows the patient well and who spends enough time with them to be able to comment on changes in cognition and behavior.

Behavioral Checklist. Current diagnostic tests focus on loss of memory and other cognitive abilities. Researchers are working on a different kind of checklist that might help identify people at risk for AD based on behavioral symptoms. The Mild Behavioral Impairment Checklist (MBI-C) looks at a collection of behaviors that can precede MCI—apathy/drive/motivation; mood/affect/anxiety; impulse control/agitation/reward; social appropriateness; and thoughts/perception. For a diagnosis of MCI, the symptoms must have continued for at least six months. The creators of the checklist say that once it has been refined, the scale may serve as a guide to researchers, as well as to family members of older adults at risk for dementia.

Blood and Urine Tests. These tests can rule out conditions that cause memory loss, such as thyroid problems, kidney or liver dysfunction, and infections. Initial screening blood tests typically include thyroid stimulating hormone, vitamin B₁₂, homocysteine, complete blood count, complete metabolic panel, erythryocyte sedimentation rate, and C-reactive protein.

Neurological Tests. Your doctor will check your coordination, strength and muscle tone, balance, eye movement, speech, and reflexes to look for other brain disorders, such as a stroke or ­Parkinson’s disease.

Brain Imaging. Your doctor may recommend brain imaging to help arrive at a diagnosis.

• Computed tomography (CT) provides a three-dimensional view of your brain to help your doctor spot a stroke or bleeding in the brain.
• Magnetic resonance imaging (MRI) identifies abnormalities in brain structure with sharper resolution than CT scans and can help doctors assess the structure of your brain.
• PET scans are used to examine brain metabolism and look for areas with reduced metabolism that may be suggestive of lower brain activity. In addition, new PET tests can identify brain amyloid or tau, although these tests  may not be covered by insurance.

New Tests for Alzheimer’s

The push within the research community is to hone in on the earliest stages of AD. Although not yet included in guidelines for clinical practice, diagnostic guidelines for research settings incorporate biomarkers and recommend that they be used in clinical trials examining the various stages of AD development. Most of these biomarkers involve either neuroimaging techniques or measurements of substances found in cerebrospinal fluid (CSF). The long-term goal is to identify accurate biomarker tests that can be  integrated into general clinical practice.

Some studies are working to make this a reality. In 2018, European researchers published preliminary results from their European Medical Information Framework for Alzheimer’s Disease Multimodal Biomarker Discovery (EMIF-AD) study, which was designed to find non-invasive biomarker tests that identify AD and predict the rate of cognitive decline.

The study involved three subgroups of participants—those who were cognitively normal, those with MCI, and those with AD. In their first round of data analysis, they noted several interesting findings: 1) the ApoE4 allele was more common in beta-amyloid positive individuals (abnormal beta-amyloid levels in CSF or by PET scan); 2) among individuals with MCI, beta-amyloid-positive individuals performed worse on cognitive tests than beta-amyloid negative individuals; and 3) beta-amyloid positive individuals in the cognitively normal and MCI groups had a faster rate of cognitive decline than the beta-amyloid negative individuals in those groups. Additional analyses are ongoing to assess other biomarkers in this population.

Another major study, supported by the National Institutes of Health and more than 30 organizations, is helping to validate a number of biomarkers to improve Alzheimer’s diagnosis. Called the Alzheimer’s Disease Neuroimaging Initiative (ADNI), the project began in 2004. Now in its third phase, it is set to run until 2022. Its researchers are investigating cognition, function, brain structure, and biomarker changes in healthy older adults, and those with MCI or AD.

These brain scans and biomarkers show promise for detecting AD:

Brain Scans

Neuroimaging techniques such as PET and MRI scans can detect changes in the brain structure that may be associated with early AD.

PET Scans. In the past, it was only possible to spot beta-amyloid plaque buildup in the brain after death. Over the last few years, researchers have been developing techniques to identify beta-amyloid plaque using PET scans. To conduct these scans requires a tracer—a substance that binds to beta-amyloid in the brain so it can be visualized.

Three molecular imaging tracers—­florbetapir F-18 (Amyvid), flutametamol F18 (Vizamyl), and florbetaben F18 (Neuraceq)—can detect beta-amyloid plaques in people with suspected AD. When these chemicals are injected into the bloodstream, they travel to the brain and bind with plaques where they accumulate between neurons, making them visible on PET scans.

Beta-amyloid PET scans are not yet a routine diagnostic tool, but research suggests they could lead to more accurate diagnoses if they were implemented more often. This is vital, since as many as 25 percent of patients in clinical trials do not have AD, leading to a lot of wasted time and reduced power to detect any real impact of the agents in these studies.

Two studies reported at the 2017 Alzheimer’s Association International Conference found that PET scans more accurately confirmed or excluded an AD diagnosis compared to current diagnostic methods. More than 80 percent of people with cognitive impairment said they’d be willing to undergo a PET scan if their doctor recommended it.

In 2015, the Alzheimer’s Association launched a four-year, $100 million research study called Imaging Dementia—
­Evidence for Amyloid Scanning (IDEAS). This study, which includes more than 18,000 Medicare recipients, will help ­assess the usefulness of PET scans for amyloid imaging.

In the first phase of the study,  researchers reported that the scans altered the medical management of both MCI and AD in over 65 percent of cases, including reducing the need for other diagnostic tests and influencing the medications used for treatment. The study was completed in 2019 and the second phase of the analysis—whether the imaging improved health outcomes—is expected to be published in 2020.

Until recently, researchers were similarly unable to hunt for tau in the brains of living individuals with suspected Alzheimer’s. But in 2015, Keith Johnson, MD, Reisa Sperling, MD, and their team at Massachusetts General Hospital for the first time used PET technology to scan patients for tau protein.

Researchers are actively studying tau tracers for use in PET imaging, with the first one, MK-6240, having been approved by the FDA in 2017. Studies have shown that tau PET scans not only aid in the diagnosis of AD, but in monitoring disease progression. They also serve as a complementary tool to measuring tau in CSF. A study published in JAMA Neurology in 2018 showed that tau PET scans predicted memory decline in individuals with familial AD.

Researchers from Massachusetts General Hospital followed a group of 12 South American patients—nine cognitively unimpaired and three with mild cognitive impairment (MCI)—with an inherited genetic mutation in the gene for presenilin 1 for familial Alzheimer’s, and compared them with 12 age-matched cognitively unimpaired people from the same community without the mutation.

They found that PET scans revealed beta-amyloid deposits roughly 15 years before the onset of clinical symptoms while tau deposits were detected closer to five years before symptoms. Levels of tau deposition were more closely associated with cognitive decline than beta-amyloid levels, with higher tau levels correlating with faster rates of decline. The findings in this small but carefully chosen sample point to the potential of tau PET scans to identify Alzheimer’s disease in a shorter, potentially more actionable, time window before the start of clinical disease.

Other research using PET scans focuses on the already approved fluorodeoxyglucose (FDG)-positron emission tomography (PET). These FDG PET scans include a labeled form of glucose and highlight areas where the brain is metabolizing sugar, and thus, is active. FDG scans are considered a measurement of neuronal injury as they can reveal areas of reduced activity in a pattern resembling AD or instead that are typical of fronto-temporal dementia (FTD). FDG PET is currently approved by Medicare and other insurers for the differentiation of AD and FTD but not for the diagnosis of MCI or early dementia.

MRI and fMRI. MRI uses radio waves and magnets to create a detailed picture of the brain and is a key tool in understanding structural brain changes.

The brain shrinkage characteristic of AD typically develops in a fairly standard pattern that can be recognized by a trained observer, and these early changes have been seen both on MRI and at autopsy. In addition, MRI also reveals not only large strokes but smaller strokes (known as lacunes) and microhemorrhages, as well as changes in the brain’s white matter (essentially the “cabling” between brain cells) that contribute to dementia, often in combination with AD pathology. Again, both MRI and autopsy studies have shown that vascular pathology plays a significant role in the development of dementia and that many older patients with Alzheimer’s disease have mixed pathologies.

Functional magnetic resonance imaging (fMRI) is a newer imaging technique that maps activity in the brain. fMRI can be used to view brain cell function and detect changes in activity that may indicate developing AD.

Low-Tech Checks. In recent years, studies have demonstrated that sophisticated scanning technology is not the only screening capable of detecting brain changes that precede dementia symptoms. Clinicians can use simple memory tests such as these:

• Memory Binding Test (or Memory Capacity Test). This test uses recall to reveal memory loss in patients without overt symptoms. It can provide clues to whether there are beta-amyloid deposits in the brain.
• Behavioral Pattern Separation-Object Test. This assesses recognition of familiar objects to detect early signs of MCI.

Biomarkers in Cerebrospinal Fluid

The brain and spinal cord are bathed in protective CSF, and the fluid is a valuable diagnostic tool for central nervous system infections and other diseases.

Over the past 20 years, as tests for certain proteins excreted into the fluid by brain cells have become available, CSF has begun to play a critical role in the diagnosis and prognosis of AD. An “Alzheimer’s profile” includes CSF tests for a form of beta-amyloid called A42, total tau (t-tau), and phosphorylated tau (p-tau).

Studies using both CSF and PET scans have increasingly demonstrated A42 to be an accurate biomarker of early disease as it appears in the CSF in many cases before beta-amyloid appears on PET scans or before clinical symptoms have become apparent in people who develop AD.

In the early years, these tests were plagued by variability between labs and relatively high error rates. More recently, advancements in diagnostic technology have helped standardize results, making them an even more important diagnostic tool for subclinical disease (in some cases the tests can detect disease 10 to 15 years before symptoms appear).

Another biomarker found in CSF, YKL-40, is a protein associated with neuroinflammation, another known factor in the pathology of Alzheimer’s. Scientists think that microglia, the cells that surround the beta-amyloid plaques, may secrete YKL-40 as part of an inflammatory response to the deposits.

An ongoing meta-analysis of CSF biomarkers updated regularly by Alzforum (a research website for the Alzheimer’s community) has shown that YKL-40 holds promise as another important CSF biomarker—both for diagnosis and predicting disease progression, although critics point out that its presence in other neuroinflammatory diseases may limit its utility.

More recently, researchers have been looking at biomarkers that reflect damage and injury at the synaptic level in the brain. Synapses are the main communication units between cells in the brain. They are composed of a pre-­synaptic area where neurotransmitters are released and transported to the post-synaptic receptors on another nerve cell. It is thought that dysfunction and degeneration of the synapses is what directly causes cognitive decline in AD.

Studies have shown that measuring a synaptic protein, neurogranin, is another accurate diagnostic tool that also may help predict the progression of the disease. Neurogranin is thought to be critical in a process called long-term potentiation which, in turn, is crucial for long-term memory formation. Studies have shown that neurogranin levels are reduced in the brains of individuals with AD but are increased in their CSF. Importantly, neurogranin does not appear to be elevated in other neurodegenerative diseases such as Parkinson’s or Lewy body dementia, making it a more specific biomarker.

Despite the increasing accuracy of CSF biomarkers and the growing number of biomarkers being studied, the invasive test needed to obtain CSF—a lumbar puncture (or spinal tap)—may be a limiting factor. Some medical professionals believe CSF biomarkers may not improve diagnostic sensitivity enough to justify the invasive procedure.

Biomarkers in Blood

Efforts to replace the need for a spinal tap with a less invasive, more easily obtainable blood draw have led to a push for developing an accurate blood test for Alzheimer’s. This has been challenging, however, because even though proteins excreted by the brain flow freely into the CSF, only a few brain proteins are able to cross the blood-brain barrier and enter the bloodstream.

Many of these efforts have focused on looking at whether levels of amyloid in the blood of people with Alzheimer’s might correlate with amyloid in the brain and CSF. Research  shows that as beta-­amyloid plaques develop in the brain, there is less of the protein available to circulate in
the blood.

In particular, the level of A42 in the blood drops, so a lower ratio of A42 to another beta-amyloid product, A40, has indicated plaque formation in the brain in past studies, but accuracy rates are  only in the 80 to 87 percent range.

Blood tests for tau are also being researched, as tau in the blood appears to correlate with tau in the brain. Tau appears later in the course of the disease, though, so its presence is better at predicting rate of cognitive decline in individuals with existing dementia.

Tau is also a target of a blood test that analyzes platelets, the component of blood involved in clotting. Researchers have noninvasively detected damaged tau protein in the platelets of people with AD. Evaluating the ratio between abnormal and normal tau protein in platelets can correctly identify people with Alzheimer’s early in the disease process.

Neurofilament light protein (NfL) has received a lot of attention lately. NfL is a structural protein found in the axon of nerve cells—the long threadlike extensions that transmit signals between nerves. When an axon is injured, NfL is released and leaks into the blood. As a result, it has proven to be a reliable marker for neuronal injury.

Studies show elevated NfL levels in a broad range of neurodegenerative conditions, which means it wouldn’t be ideal for differentiating one neurologic condition from another. However, it may hold promise as a reliable means of tracking disease progression.

Another area of research involves the field of epigenetics or the study of how modification of gene expression (as opposed to changes in the actual genetic code itself) impacts health. MicroRNAs are small non-coding RNA molecules (containing about 22 nucleotides; RNA is ribonucleic acid, a nucleic acid present in all living cells).

MicroRNAs are involved in a variety of biological processes, including the cell cycle, and regulate gene expression. Researchers have identified certain microRNAs whose levels in blood appear to correlate with AD. Studies using panels of microRNAs in the blood to diagnose AD have demonstrated accuracies as high as 95 percent, though the tests are still at an early stage of development.

Some researchers believe that a panel of blood biomarkers may be a better way to diagnose AD than a single marker assay. Over the past 10 years, researchers have investigated panels that measure a broad range of biomarkers including inflammatory proteins. One of the first large studies to do so demonstrated highly accurate results, but subsequent researchers were not able to replicate the results.

Recently, however, researchers from Cardiff University in Wales published results of a study evaluating a 53-­biomarker panel in 199 patients with MCI, 262 with AD, and 259 cognitively normal controls in the June 2019 issue of the Journal of the Alzheimer’s Association. They found that 10 of the inflammatory protein biomarkers could be used to accurately distinguish individuals with AD from controls when patients’ age and ApoE4 status were accounted for.

Research presented at the 2018 Alzheimer’s Association International Conference indicates that the measurement of certain bile acids, including some produced in the liver and some produced by bacteria in the gut, correlates with AD biomarkers such as CSF beta-amyloid and tau, along with changes in brain volume. Similarly, other research has linked levels of certain lipids, important components of cell membranes, to AD. Experts say these findings highlight the connection between our brains and gastrointestinal tract, providing new direction for further research along with underscoring the potential for diet to impact disease.

A saliva test might be an even easier, noninvasive way to detect changes associated with AD. Investigators are using technologies such as liquid chromatography-mass spectrometry (LCMS) and metabolomics (the study of small molecules called metabolites in blood, saliva, and tissues) to identify unique substances in saliva of people with AD but not in those with normal cognitive function.

None of these tests have reached the commercial market, as of yet. Results from initial studies for noninvasive diagnostic tests need to be validated on larger scales before they can move from the research arena to clinical practice. Experts agree, however, that the latest findings hold promise for that transition.

Focusing on the Senses

New tests for Alzheimer’s may rely on our ability to smell, see, and hear as an early warning system.

Smell Tests. As AD begins to affect the brain, it often touches cells important to the sense of smell, making it harder for a person to distinguish between various scents. Smell testing might be a useful tool to predict progression to dementia in older adults at risk.

Researchers are studying several scent-based diagnostic tools. The University of Pennsylvania Smell Identification Test (UPSIT) was developed as an easy way to diagnose Alzheimer’s early, without the need for expensive brain scans. The 40-item test has limitations, however, including the fact it doesn’t consider differences in smelling ability among healthy people.

A team at Massachusetts General Hospital tried to improve the UPSIT with a battery of four scent-based tests. In a study published in Annals of Neurology, their tests were able to accurately distinguish between people with normal cognitive functioning and those with MCI and AD. One of the tests, the Odor Percept Identification Test-20 (OPID-20) involved exposing participants to 20 different scents for two seconds each.

Participants were then given four words and asked which word they thought best described the odor. Researchers found that patients who performed poorly on the OPID-20 were more likely to have thinning in the hippocampus and entorhinal cortex, which are areas of the brain  associated with Alzheimer’s. In a study published in 2019, Japanese scientists also demonstrated that poor performance on a smell test correlated with worse scores on a cognitive assessment test (ADAS), and with degree of atrophy in an area of the brain commonly affected in AD.

Despite the promise of a scent test for predicting Alzheimer’s, other medical problems including sinus disease and allergies, also can lead to an impaired sense of smell. Any smell tests developed to detect AD must be able to distinguish between it and other medical causes.

Sight Tests. Changes in the retina (a layer of light-sensitive cells at the back of the eye) may offer a window into the disease. People with AD show signs of reduced blood flow and cell loss in the retina compared to individuals with normal cognition. Problems with contrast sensitivity, visual field, depth, motion, and color perception also can indicate Alzheimer’s. As with smell, it’s important to distinguish between AD and common eye diseases, such as glaucoma. However, the eyes could prove a noninvasive, inexpensive new pathway for AD diagnosis.

Alzheimer’s Risk Scores

Doctors don’t have a crystal ball for predicting a patient’s cognitive future, but researchers are working on ways to help predict the likelihood of developing AD.

The most recent Alzheimer’s prediction method comes from the University of California with a test called the polygenic hazard scoring system, which can predict the age at which someone might develop AD based on 31 genetic markers.

In a 2017 study, the researchers demonstrated that even when controlling for ApoE4 status, the system was effective in predicting time to dementia and risk for cognitive decline in asymptomatic individuals. More work needs to be done, but this system may help identify candidates for clinical trials.

In Sweden, researchers developed an AD prediction method based on age, education, gender, systolic blood pressure, body mass index, blood cholesterol, and physical activity. By combining these scores, the researchers identified people at high risk for developing dementia within 20 years, so lifestyle changes can be made. The model shows promise but needs more research to determine whether altering these risk factors will change dementia outcomes.

A large international effort, called the International Genomics of Alzheimer’s Project (IGAP), has studied thousands of patients since 2011 in an effort to not only discover and map all of the genes that contribute to AD but also to identify less common variants that may influence a person’s risk. The hope is that this knowledge will help predict someone’s risk of developing AD in addition to pointing the way to new treatment options.

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