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Read web-exclusive content related to articles published in print.

Friday, April 14, 2017

Exercise and Dementia.jpeg

In the June/July 2017 issue, we look at the differences between how women and men experience neurologic disease and the subsequent emergence of sex-specific research. Understanding sex and gender differences may improve diagnosis, treatment, and outcomes for women. In this online exclusive, we address some of the psychosocial challenges women face after a diagnosis and how to manage them.


For women, who often serve as the emotional bedrock for their family and household, life may become extra challenging after a diagnosis of a chronic neurologic disease. Some families rise to the situation, while others struggle.

"Women [with neurologic diseases] don't always get the support they need from their spouses," says Maria De Leon, MD, a neurologist and movement disorders specialist in Nacogdoches, TX, and research advocate for the Parkinson's Foundation. "Women have higher divorce rates after being diagnosed with a neurologic disease. Their spouses say, 'This is not what I signed up for.'"

To counter the negative effects of a chronic neurologic condition, keep these strategies in mind.

Mind your health. Make taking care of yourself a top priority, even when you're juggling caring for children or elderly parents and perhaps working. That means getting enough sleep, eating well, exercising regularly, and finding ways to manage stress. "Taking care of yourself when you don't feel well can help make you feel better," Dr. De Leon says.

So can asking for help when you need it and recognizing (and honoring) your personal limits. Six months after the birth of her daughter in 2004, Stephanie Taylor, an author and high school teacher in Vancouver, WA, was diagnosed with MS. "I was lucky that I got a fast diagnosis, but I had an infant to care for as I navigated my first flare-ups," says Taylor. "My husband and I decided not to have more children because of my MS. I want to be there for my daughter and be the best and healthiest mom I can be."

Tell your doctor about side effects. Medication side effects aren't unique to women, but some may bother women more than they do men, says Dr. De Leon. For example, divalproex sodium (Depakote), pregabalin (Lyrica), and perampanel (Fycompa) can cause weight gain. "If a drug causes weight gain, some of my female patients are more reluctant to take it," says Jacqueline A. French, MD, FAAN, professor of neurology at the New York University Comprehensive Epilepsy Center and chief scientific officer for the Epilepsy Foundation. Similarly, hair thinning can occur with the anticonvulsant drugs levetiracetam (Keppra) and divalproex sodium, while others such as phenytoin (Dilantin) can cause excessive hair growth—side effects that may be unacceptable to some women.

If you experience these types of side effects and consider them intolerable, discuss them with your doctor to find ways to mitigate them. Your doctor might try another drug that can treat your condition effectively without causing those unwanted side effects.

Stay connected. Reach out to friends and extended family. It's important not to isolate yourself, even if some former friends can't handle your diagnosis.

After Carol Poole, who has early-stage Alzheimer's disease, told people about her diagnosis, some women in her social circle reacted badly and shunned her. "Some people seem to think it's contagious and don't want to have anything to do with me," says Poole, who used to be the president of several civic organizations. "They act as if I'm not here intellectually in the same way I once was. That's frustrating for me. Social engagement is so important because the more you withdraw, the more depressed you get." (This is a particular risk for women, since they are already more vulnerable to depression than men.)

Fortunately, Poole's extended family and some trusted friends rallied around, and she began participating in a support group for people with early-stage Alzheimer's disease once a month, which buoyed her mood. Joining a support group can make a significant difference. So can spending time with supportive friends and participating in interest-based social activities, whether it's joining a book club or volunteering at a museum or charitable organization.

Wednesday, March 15, 2017

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In the April/May 2017 issue, we speak to Marcia Gay Harden about her mother's diagnosis of Alzheimer's disease and how that motivated Harden to become an advocate for people with the disease. In this online exclusive, we describe several of the Alzheimer's disease clinical trials currently underway.


More than 400 clinical trials are currently studying new treatments for Alzheimer's disease, and many are actively recruiting participants. Here are a few.

Engage and Emerge

Aducanumab, a monoclonal antibody thought to target clumps of beta amyloid, is currently being evaluated in two global phase 3 studies, ENGAGE and EMERGE. Based on preclinical and phase 1b data, aducanumab has been shown to reduce amyloid plaque levels. The phase 3 trials are designed to evaluate the drug's safety and efficacy in slowing cognitive impairment and the progression of disability in people with early Alzheimer's disease. For more information, visit engageandemerge.com.

Anti-Amyloid Treatment in Asymptomatic Alzheimer's

The Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) study at Brigham and Women's Hospital in Boston is currently recruiting participants, says lead investigator Reisa A. Sperling, MD. The trial will measure the effectiveness of the experimental therapy solanezumab, an anti-amyloid antibody that may slow memory loss associated with amyloid buildup. The trial is aimed at delaying memory decline in older individuals who have amyloid plaque buildup in their brains but still have normal memory.

In previous studies, solanezumab did not show a beneficial effect in more than 1,000 people who did not exhibit any symptoms of Alzheimer's disease, says Dr. Sperling. But the participants in the A4 study are about 10 years earlier in their disease trajectory than the patients studied in previous solanezumab trials, she says. "This is a very similar prevention approach to what has been successful in diabetes and heart disease, such as using statins in individuals with elevated cholesterol before they have a heart attack or stroke," she says.

Volunteers must be 65 to 85 years of age with normal thinking and memory function and no outward signs of dementia, Dr. Sperling says. The researchers will use a PET scan to determine whether the participants have an elevated level of amyloid plaque in their brains. For more information, visit A4study.org or call 844-A4STUDY.


The phase 3 clinical trial known as TOMMORROW, which completed enrollment last year, is one of the largest to look at mild cognitive impairment (MCI) due to Alzheimer's disease. The five-year randomized, double-blind, placebo-controlled, parallel-group trial, funded by Takeda Pharmaceuticals and Zinfandel Pharmaceuticals, involves approximately 3,500 people between the ages of 65 and 83 at centers in the United States, the United Kingdom, Germany, Switzerland, and Australia.

Researchers are investigating whether identifying specific genes is a valid way to assess the risk of MCI due to Alzheimer's disease in people older than 65. One of these genotypes is TOMM40, which inspired the study's name. They are also evaluating the safety and efficacy of pioglitazone, a drug currently used to treat type 2 diabetes, for postponing the onset of MCI in people with normal cognitive function who are considered to be at high risk for Alzheimer's disease. Research suggests that pioglitazone works by increasing the sensitivity of cells to insulin and regulating glucose levels, which are abnormal in both diabetes and Alzheimer's disease, and suppressing inflammation, which is also linked to both conditions.

Dominantly Inherited Alzheimer Network Trials Unit

Formed in 2012 at Washington University in St. Louis, the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) designs and directs trials for people with or at risk for dominantly inherited Alzheimer's disease, a rare form of the condition caused by a gene mutation, which is responsible for less than 1 percent of all cases of the disease. Mutations in the amyloid precursor protein (APP), presenilin 1 (PSEN-1), or presenilin 2 (PSEN-2) are associated with developing Alzheimer's disease at a young age, usually in the 30s, 40s, or 50s.

A phase 2/3 randomized, double-blind, placebo-controlled trial is currently underway to test the experimental drugs gantenerumab and solanezumab for safety, side effects, and effects on imaging and biomarkers in people who know they have a genetic mutation, as well as those who don't know their genetic status but have a 50 percent chance of having a mutation because a parent or sibling has one. The researchers will evaluate them for subtle changes in cognition, but participants at this early stage are not likely to have more than minimal changes during the study period.

Alzheimer's Prevention Initiative

Last year, the Banner Alzheimer's Institute in Phoenix, AZ, launched the Alzheimer's Prevention Initiative (API), an international, collaborative research team formed to study ways to prevent the disease. The group currently has two five-year trials underway in individuals who are cognitively well but have the highest risk for developing Alzheimer's symptoms.

In the first, the API Autosomal Dominant Alzheimer's Disease (ADAD) trial, researchers are testing the efficacy and safety of crenezumab, a monoclonal antibody that that helps to remove amyloid beta protein from the brain, in members of an extended family in Medellin, Colombia, who carry the PSEN1 E280A autosomal dominant mutation, which makes it a certainty that they will develop the disease at an average age of 44.

In the other trial, the API Generation study, scientists are investigating whether two experimental therapies—an active immunotherapy (CAD106) and a beta-secretase 1 inhibitor (CNP520) can prevent or delay the disease in 1,300 cognitively healthy older adults between the ages of 60 and 75 who are at high risk of developing Alzheimer's disease because they have two copies of the risk gene apolipoprotein 4 (one from each parent).

Learning from Failure

"We have seen several clinical trials across the country that were unsuccessful," Dr Sperling says. "Yet even unsuccessful trials provide us with new clues about the disease." Consider the anti-amyloid therapies solanezumab, crenezumab, and bapineuzumab, for example, . In trials involving people with mild to moderate Alzheimer's disease, none has significantly slowed cognitive decline or improved global functioning. But at higher doses, the drugs have had an effect on those with mild forms of the disease, which supports the theory that to treat the disease, therapy must begin at a much earlier stage, well before symptoms appear.

Both Dr. Aisen and Dr. Sperling emphasize the urgent and ongoing need for clinical trial participants. For information on other Alzheimer's disease clinical trials in your area, visit alz.org or clinicaltrials.gov and type in "Alzheimer's disease."


Wednesday, March 15, 2017


In the April/May 2017 issue, we interview Marcia Gay Harden about her mother's experience with Alzheimer's disease as well as Harden's newest role as an advocate for people with the disease. In this online exclusive, we explore the latest research efforts to find disease-modifying therapies.


Long before people with Alzheimer's disease show signs of cognitive decline, plaques made of the beta-amyloid protein and twisted fibers of the tau protein begin to form in their brains. "The disease starts 10 to 15 years before a person begins experiencing dementia symptoms," says Paul Aisen, MD, director of the Alzheimer's Therapeutic Research Institute at the Keck School of Medicine at the University of Southern California in Los Angeles. By the time someone reaches age 65, he or she has a 10 percent chance of developing Alzheimer's disease. That risk increases to 50 percent by age 85.

As the Baby Boomer generation continues to age, the number of people with Alzheimer's disease could triple to 13.8 million by the year 2050, according to the Alzheimer's Association. "It's one of the most feared consequences of aging," says Dr. Aisen.

Knowing that brain damage begins before symptoms appear, researchers are studying anti-amyloid therapies that could be applied in the pre-symptomatic stage when they may be most effective, he says.

Taking Aim at Amyloid

Drugs such as aducanumab, an experimental therapy being developed by the pharmaceutical company Biogen, have shown promise in reducing the accumulation of toxic plaques found in the brains of people with Alzheimer's disease and slowing cognitive decline, says Dr. Aisen.

In preclinical research and a small phase 1b placebo-controlled study published in Nature in September 2016, researchers found that treatment with aducanumab resulted in a significant reduction of plaque buildup. They also found that a higher dose resulted in slower cognitive decline, as measured on tests of memory and thinking skills. "If confirmed by additional clinical trials, aducanumab would represent a true breakthrough in the fight against Alzheimer's disease," Dr. Aisen says.

Improving Detection

Current research combined with the ability to detect the disease earlier and earlier will ultimately lead to new therapies, Dr. Aisen says. New biomarker tests such as positive emission tomography (PET) scans and drawing cerebrospinal fluid (CSF) from a lumbar puncture—in the early stages, the disease may cause changes in CSF—can help doctors accurately determine who is going to develop Alzheimer's disease, he says. They also aid researchers in their quest to create a pre-Alzheimer's test that will help tailor preventive treatments. "Within the next five to 10 years, I believe we will have some effective disease-modifying treatments for this disease," he says.

Several drug candidates are in clinical trials right now, including AADvac1, a vaccine that stimulates the body's immune system to attack an abnormal form of the tau protein that destabilizes neurons, and CSP-1103, a microglial modulator—microglial cells clear out debris and toxins in the brain and are known to malfunction in Alzheimer's disease—that targets inflammation.

Leaky capillaries (blood vessels) in the brain may also contribute to Alzheimer's disease, according to a theory formulated by Berislav Zlokovic, MD, PhD, a colleague of Dr. Aisen's, director of the Zilkha Neurogenetic Institute (ZNI) and the Center for Neurodegeneration and Regeneration at ZNI and professor and chair of the department of physiology and biophysics at the Keck School of Medicine. Through grants from the National Institute on Aging, the National Institute of Neurological Disorders and Stroke, the Alzheimer's Association, and the Fondation Leducq in Paris totaling $24.9 million over five years, Dr. Zlokovic is studying whether fixing these leaks 10 to 15 years before symptoms surface can slow the onset or progression of the disease.

Preventive Therapies

Dr. Aisen also believes that a preventive therapy akin to statins, which help lower cholesterol, is within reach in the next few decades. "By identifying high-risk patients, we can measure amyloids the way we measure cholesterol and prescribe a BACE inhibitor, a type of drug that blocks the enzyme involved in the production of protein plaques associated with Alzheimer's," Dr. Aisen says. "The hope is this approach would prevent the buildup of plaque in the first place."

Wednesday, March 8, 2017

​In the April/May 2017 issue, we feature a guide to summer camps for children with neurologic disorders. In this online exclusive, we ask the experts what parents should ask before choosing a camp.


Once you've identified a camp or camps that you think might be a good fit for your child, it's time to check them out further. Start with these questions.

  1. What age ranges does the camp serve?
  2. How long is the camp?
  3. What activities are available?
  4. What is a typical day like?
  5. What kind of medical staff do you have?
  6. What training do medical staff have to address my child's condition?
  7. What is the counselor to camper ratio?
  8. Can you add staff for kids with particularly complex needs?
  9. What are the facilities like? (Most of these camps run for only a few days or a week every summer, so they aren't housed in their own purpose-built facilities. Instead, they often make temporary use of the facilities of other summer camps, such as YMCA camps.) 
  10. What types of medical facilities do you have?
  11. What plans are in place to address medical emergencies or problems?
  12. What types of adaptive equipment/facilities are available?
  13. What is the cost?

Are scholarships available? (Many programs for kids with neurologic conditions are offered at either no cost or at very minimal expense to the families.)

Friday, February 3, 2017

MS exercise.jpeg 

In the February/March 2017 issue, we profile Jamie-Lynn Sigler who kept her diagnosis of multiple sclerosis (MS) a secret for 15 years. She decided to go public in part because she didn't want her 3-year-old son, Beau, to have to keep her disease a secret. Today, she is an active member of the MS community and blogs about life with a chronic neurologic disease. In this online exclusive, we share tips for how to stay healthy and reduce the risk of complications from MS.


There is no cure yet for multiple sclerosis (MS), but medication combined with a healthy lifestyle can help people stay fit, prevent complications, and maximize function, says Barbara S. Giesser, MD, FAAN, clinical director of the MS program at the David Geffen School of Medicine at UCLA and co-author of Navigating Life with Multiple Sclerosis, a book in the American Academy of Neurology's Neurology Now Books series.

1. Move more. A combination of cardiovascular exercise, stretching, and strength training can ease symptoms of fatigue, stiffness, and depression, says Dr. Giesser, who recommends exercising 20 to 30 minutes, three to four days a week. Walking, either outside or on a treadmill, and swimming are both great exercises. "In the water, where gravity is eliminated, people with limited mobility often can do things they couldn't do on land. They also won't get overheated, which may temporarily worsen some symptoms," she says. "Riding a stationary bicycle or using an elliptical trainer is also a good way to exercise. Everyday physical activities such as walking the dog or housework are also beneficial."

If fatigue is a problem, Dr. Giesser suggests breaking exercise into 10-minute increments throughout the day to build up endurance. She also recommends yoga, which she says has been shown to improve mood and flexibility and reduce fatigue. The National MS Society offers adapted yoga classes across the country. To learn more go to bit.ly/NMSS-Yoga.

2. Mind your diet. No specific diet has been proven to help MS patients, but a well-rounded plan such as the Mediterranean diet, which emphasizes fruits and vegetables, whole grains, legumes and nuts, and less red meat and fewer saturated fats and refined grains, has been associated with a lower risk of cognitive decline, heart disease, and diabetes, says John Corboy, MD, FAAN, professor of neurology at the University of Colorado Denver School of Medicine and co-director of the Rocky Mountain Multiple Sclerosis Center at Anschutz Medical Campus.

3. Get healthy. "Losing weight and quitting smoking can help MS patients improve their quality of life and possibly even slow the progression of the disease," says Dr. Corboy. Adequate sleep—at least seven hours a night—is also important, says Patricia K. Coyle, MD, FAAN, professor and acting chair of neurology and director of the Multiple Sclerosis Comprehensive Care Center at the Stony Brook University Medical Center in Stony Brook, NY.

4. Up your vitamin D. The optimal source for vitamin D is sunlight—10 to 20 minutes a day between 11 a.m. and 4 p.m.—but many people don't get enough. Dr. Corboy suggests getting vitamin D levels tested regularly and talking to your neurologist about what he or she considers to be an optimal level and whether or not you need supplementation.

5. Stay mentally active. Brain health is as important as physical health, says Dr. Coyle, who recommends staying socially engaged and intellectually stimulated through play and learning and studying.