The Tangled Neuron

Are You at Risk for Drug Interactions?

Summary:  A recent study suggests that some older adults are at risk for potentially dangerous drug interactions.  Make sure your doctor and your pharmacist are aware of all the supplements, prescription and over-the-counter medicines you take, and ask them to check for potential interactions.

In online forums and at meetings, I hear people with memory loss talk about the medicines and supplements they take.  It’s not unusual for them to reel off a list of several prescription drugs and twenty or more supplements.  Could the combination of some of these medicines be dangerous?

Dima Qato, PharmD, MPH

Potential drug interactions are a concern for everyone, not just for people with memory loss.  Late last year, the Journal of the American Medical Association published an article by Dr. Dima Qato and her colleagues at the University of Chicago on the medicines older Americans take.  The researchers catalogued the drug use of over 2200 people across the U.S., ages 57 through 85.

Anticholinergic Medicines and Memory Loss

Summary:  commonly-used prescription and over-the-counter drugs may contribute to memory loss in older people, particularly if taken for long periods of time.

Results of a recent study by scientists at Yale University suggest that long term use of some prescription and over-the-counter medicines contributes to memory loss in older people.  Previous studies, including one by French researchers, had also shown a connection between these medicines and memory loss.  The Yale study, which quantified the effects of using multiple anticholinergic medicines over time, confirmed this connection.  For study participants (544 men 65 and older), cumulative exposure to these medicines over a year’s time was associated with lower scores on tests of short term memory and executive function.  The study authors believe that the medicines have a similar effect on women.

The Mediterranean Diet, Mild Cognitive Impairment and Alzheimer's

Summary:  Following the Mediterranean diet may reduce your risk of Mild Cognitive Impairment and Alzheimer’s, and may increase the lifespan of people already diagnosed with Alzheimer’s.

Nikos Scarmeas, MD

Dr. Nikos Scarmeas, Assistant Professor of Clinical Neurology at the Taub Institute for Alzheimer’s and the Aging Brain at Columbia University, studies the connection between diet and Alzheimer’s.  Now he’s extended his research to include the connection between diet and Mild Cognitive Impairment (MCI), and has co-authored an article in this month’s Archives of Neurology about that research.

The new article and much of his recent research centers around the Mediterranean diet, and the results are encouraging.  In several large population studies, he and his colleagues have found:

People who closely follow the Mediterranean diet have a lower risk of developing MCI (28% lower than those who don’t follow the diet very closely over a 4.5 year study period)

Exercise, Blood Sugar and Memory Loss

Summary:  Physical exercise helps you maintain normal blood sugar levels, and may reduce your risk of memory loss.

In my last post, I wrote about how reduced blood flow to aging brains decreases the amount of glucose available to brain cells.  This may trigger a series of events contributing to Alzheimer’s.  But just as too little glucose is a problem, too much can also be harmful.

Scott A. Small, MD

A new study by Dr. Scott Small and colleagues at Columbia University links age-related increases in blood sugar [glucose] to damage in an area of the brain called the dentate gyrus.  The dentate gyrus is part of the hippocampus, an area thought to be involved with short term memory.  The researchers think this may explain how high blood sugar, even in people without full-blown diabetes, can contribute to “normal” age-related memory loss.

Exercise, Blood Flow and Alzheimer's

Summary:  A new study by Northwestern University researchers details the biochemistry of how reduced blood flow to aging brains might contribute to Alzheimer’s.  Regular exercise is the best way to improve that blood flow.

Have you made a New Year’s resolution to improve your diet and exercise?  If so, it might reduce your risk of Alzheimer’s.  A growing number of studies link lifestyle factors such as poor diet and lack of exercise to dementia, but it’s unclear exactly how these factors might contribute to the plaques and tangles some researchers think are responsible for the disease.

Robert Vassar, Ph.D.

A new study by Dr. Robert Vassar and his colleagues at Northwestern University sheds light on one mechanism by which lifestyle might contribute to Alzheimer’s pathology.  They conducted a complex series of experiments to show that reducing the amount of glucose available to brain cells sets off a chain reaction that increases beta amyloid, the protein involved in Alzheimer’s plaques. 

Balance and Memory Loss (Part 2): Can Physical Therapy or Exercise Help?

In my last post, I wrote that some people with cognitive problems also have balance problems, and that many of them think these problems could be related.  Recent research at Rush University seems to confirm that view:  scientists there found that “impaired motor function” is increased in people with mild cognitive impairment, and is related to their risk of developing Alzheimer’s.

If you have both memory loss and balance problems, can physical therapy improve your balance?  “There are fierce proponents of this postulate,” says Joseph Friedman, MD, Director of the NeuroHealth Parkinson's Disease and Movement Disorders Center in Warwick, Rhode Island and Clinical Professor at Brown University Medical School. “My own belief is that exercise of all types is useful and that therapy is therefore useful but ONLY if the exercise program is maintained.”  He says his patients with dementia are more likely to stick to their exercise routine with caregiver participation and encouragement.

Balance and Memory Loss (part 1): Are Physical Symptoms Connected to Alzheimer's?

On the plane back from visiting my mom for Thanksgiving, I read Scott McCredie’s Balance: In Search of the Lost Sense.  An entire chapter in the book is devoted to improving cognitive function by improving balance.

The chapter in Balance is mostly about people with learning disabilities, and about the vestibular systems in the inner ears.  It is not about Alzheimer’s or other types of dementia.  But it got me to wondering about any connection between balance problems and memory loss.

Another Study Links Poor Diet and Alzheimer's

Another study has linked poor diet to Alzheimer's, at least for mice bred to develop the plaques and tangles in the brain associated with the disease.

Researchers at Laval University in Quebec found that feeding these mice a diet high in fat but low in Omega-3 fats increased the level of the proteins that make up plaques and tangles in the brain.  The scientists did not test whether this affected memory or performance in the mice.

Results of mouse studies don’t always hold up when applied to people.  But it can't hurt to eat a healthier diet in hopes of preventing Alzheimer’s and other diseases.

Two Different Approaches to Alzheimer's Prevention (Part 3 of 3)

The new Environmental Threats to Healthy Aging report includes a list of things you can do to reduce your risk of Alzheimer’s and other diseases.

Part 3 of a Tangled Neuron series on prevention summarizes these recommendations.

Two Different Approaches to Alzheimer's Prevention (Part 2 of 3)

Jill Stein, MD

A new report published by Greater Boston Physicians for Social Responsibility and the Science and Environmental Health Network says environmental and lifestyle factors, not just genes, are major contributors to neurodegenerative diseases such as Alzheimer’s.  The report lists a broad range of ecological, health care, and lifestyle-related steps governments, communities and individuals can take to prevent Alzheimer’s and other diseases.   

In Part 2 of a Tangled Neuron series on prevention, one of the primary authors of this report, Jill Stein, MD, talks about the science behind the new report.

Two Different Approaches to Alzheimer's Prevention (Part 1 of 3)

The Alzheimer’s Study Group is proposing increased government funding and changes to government agency structures and rules to help bring Alzheimer’s prevention drugs to market.  Part 1 of a Tangled Neuron series on prevention focuses on this group’s draft proposals.

Study Finds Ginkgo Doesn't Prevent Alzheimer's or Dementia

The results of the GEM study (Ginkgo Evaluation of Memory) study have been published: six years of taking ginkgo biloba did not prevent Alzheimer’s or other dementias in adults 75 or older. 

The study was focused on prevention, and did not address whether ginkgo was effective in treating Alzheimer’s or other dementias.  German researchers presented a study at ICAD this summer that showed ginkgo improved both psychiatric and cognitive symptoms in people diagnosed with mild to moderate Alzheimer’s disease or vascular dementia.  Results of other treatment studies have been mixed.

Beyond Drugs: Other Ways to Treat Alzheimer's and Dementia (Part 4 - Pyschosocial Risk Factors in African-Americans)

Summary:  The level and effect of psychosocial risk factors for Alzheimer's may not be the same for African-Americans and Whites.  This could mean we need different methods to prevent, diagnose and treat cognitive problems in African-American and White populations.  Large-scale studies are needed to confirm this finding.

Alzheimer's is equal opportunity and color blind, right?  Well, not exactly.  We already know that some risk factors, such as diabetes, are more common among African-Americans.  And we know that other risk factors, such as the APOE4 gene variation, may affect African-Americans differently than Whites.  But what about psychosocial factors such as emotional states or the strength of social networks? 

Lisa Barnes, Ph.D.

Dr. Lisa Barnes gave a presentation on "Psychosocial Factors and Cognition in African-Americans and Whites" during the "Psychosocial Issues and Neuropsychology" session at ICAD 2008.  Dr. Barnes, who is Associate Professor of Neurological Sciences and Behavioral Sciences at the Rush Alzheimer's Disease Center, sent me some additional information via email to round out my understanding of her work.

The data she presented at ICAD was from participants in three large, ongoing studies at Rush:  the Chicago Health and Aging Project, the Memory and Aging Project and the Minority Aging Research Study.  In these populations, she and her colleagues (including Dr. Robert Wilson) have found the following differences in the level of psychosocial risk factors between the two races:

• African-Americans are more likely to experience negative emotions or distress than Whites
• African-Americans tend to experience more depression than Whites
• African-Americans report lower levels of social engagement than Whites. 

International Conference on Alzheimer's Disease (ICAD) 2008

Summary:  the majority of presentations at ICAD focused on Alzheimer's as a disease, and what we can do to cure it.  But the presentations on healthy brain aging (even in people with Alzheimer's plaques and tangles in their brains) were just as interesting.  From my layperson's point of view, we may learn as much from exploring healthy brain aging as we do from looking for an Alzheimer's cure.

It's hard to summarize ICAD 2008, held last week in Chicago.  The majority of the hundreds of oral presentations and thousands of poster presentations focused on molecular biology (genes, proteins, etc.), and on amyloid protein in particular.  But the three presentations in the plenary session on the last day highlighted that there are at least two ways to look at Alzheimer's: 

1. as a disease, with the focus on what can we do to cure it
2. as the opposite of successful aging, with the focus on what keeps our brains healthy as we age.

Paul Aisen, MD, now at University of California - San Diego, gave a presentation called "The Evolution of Alzheimer's Disease Clinical Trial Design."  His presentation was from the view of Alzheimer's as a disease, and what we can do to cure it.

Surgery, Anesthesia and Memory Loss

Summary:  After surgery, many people experience short-term delirium and/or longer-term cognitive decline.  Scientists are still studying how to prevent these problems.

Doctors, families and patients report that surgery seems to cause short-term delirium and/or longer term memory loss in some people.

In a recent Duke University study of 1064 patients undergoing major surgery (but not heart surgery), neuropsychological tests showed the following rates of post-operative cognitive dysfunction or POCD:

Age range                  Leaving hospital      3 Months After Surgery

18-39 year olds                 37%                                 6%     

40-59 year olds                 30%                                 6%

60 or older                         41%                               13%

Zhongcong Xie, M.D., Ph.D.

Even higher rates of POCD have been reported after heart surgery, but scientists still don't agree on how to measure these problems, or on whether the heart patients also had memory loss before their surgeries.

Dr. Zhongcong Xie, Assistant Professor at Massachusetts General Hospital and Harvard Medical School, is working with his colleagues to determine what causes POCD.

POCD seems to be worse among the elderly, but "the reason why age is a risk factor for POCD remains to be determined," Dr. Xie says.  In his lab, he and his colleagues are researching

Ibuprofen, Naproxen and other NSAIDs for Alzheimer’s

Large observational studies have linked regular use of painkillers such as ibuprofen (Advil) and naproxen (Aleve) with lowered risk of Alzheimer’s, but clinical trials have not backed this up. The publication of the results of two new studies this month didn’t do much to resolve this issue. In the first study, Boston University researchers analyzed the medical records of hundreds of thousands of military veterans, and found long-term use of NSAIDs (non-steroidal anti-inflammatory drugs), particularly ibuprofen, was associated with a reduced risk of Alzheimer’s.

A detailed analysis of the results of the second study, ADAPT (Alzheimer's Disease Anti-inflammatory Prevention Trial), was published this month. It showed that neither naproxen nor another NSAID, celecoxib, improved thinking and memory in more than 2000 men and women 70 years and older who had a family history of Alzheimer’s. Naproxen actually seemed to worsen cognition. The trial was stopped early because scientists worried about the side effects of the two painkillers.

Differences in study design could explain these conflicting results.

Constantine Lyketsos, MD, MPH

The various studies tested different NSAIDs at different dosages in different populations for different lengths of time. It’s also possible that there were “confounding factors” in the population studies – maybe people who take NSAIDs had later onset of Alzheimer’s because they had higher education levels or better overall health, for example.

So, what DO we know about NSAIDs and memory loss? “After the onset of dementia, anti-inflammatory treatment does not seem to work,” says Dr. Constantine Lyketsos, one of the researchers involved in ADAPT. “The data are pretty strong.” Dr. Lyketsos is Director of the Memory and Alzheimer’s Treatment Center at Johns Hopkins University and Chairman of the Department of Psychiatry at Johns Hopkins Bayview Medical Center. 

If treatment with NSAIDs does not seem to be effective, what about prevention?

Aspirin: Good or Bad for your Memory?

Summary: Two recent studies do not show that aspirin helps memory loss. The painkiller may increase the risk of bleeding in the brain.

When my father first complained about his memory, his doctor told him to take a baby aspirin every day. After seeing headlines like “An aspirin a day to keep Alzheimer’s away?” I thought this was good advice.

Aspirin is one of several NSAIDs (non-steroidal anti-inflammatory drugs) that have been tested for prevention or treatment of memory loss. Results from two recent studies make it less likely your doctor will recommend the drug for memory loss.

Webcast: The Myth of Alzheimer's

If you want to congratulate Dr. Peter Whitehouse and Danny George for writing their book The Myth of Alzheimer’s, let them know how wrong you think they are, or are just plain curious, here’s your chance. They’ll be featured on a HealthTalk webcast tomorrow night (Wednesday, May 14th) at 7 PM eastern. Details are on the registration page at the HealthTalk site.

Does Depression Increase Your Risk of Memory Loss?

Summary: A new study provides more evidence that depression may be a risk factor for Alzheimer’s.

People with dementia often report they suffered from depression before they developed serious problems with memory and thinking. Study after study has shown a link between depression and memory loss. Researchers continue to debate whether depression increases the risk of developing serious memory loss or is simply a sign of brain changes underlying Alzheimer’s or other dementias.

Robert S. Wilson, Ph. D.

Dr. Robert Wilson, Professor of Neurological Sciences and Psychology at Rush University Medical Center, studies the neurobiology of the connection between depression and dementia. In an article in a recent issue of the Archives of General Psychiatry, he and his colleagues provide more evidence that depression may be a risk factor for Alzheimer’s.

The Alzheimer's Answer: a new book

Summary: Dr. Marwan Sabbagh’s new book The Alzheimer's Answer: Reduce Your Risk and Keep Your Brain Healthy is a handbook for baby boomers hoping to prevent serious memory loss.

Dr. Marwan Sabbagh is a geriatric neurologist and Alzheimer’s researcher at Sun Health Research Institute in Arizona. He spends his days seeing memory loss patients and their families, and supervising Alzheimer’s clinical trials. He helped care for his mother-in-law when she suffered from dementia. Like all of us who have watched family members struggle with memory loss, he worries about how it will affect his generation and his children’s.

Marwan Sabbagh, MD

For a man who admits to a fear of aging, he has deep personal relationships with the elders in his community. He calls Alzheimer’s “the embodiment of all that is sad and destructive about growing old,” and spends a lot of time thinking about what contributes to successful aging.

Looking at both the personal and the societal costs of Alzheimer’s, Dr. Sabbagh has come to the conclusion that our approach to memory loss must emphasize prevention. This is message of his new book The Alzheimer's Answer: Reduce Your Risk and Keep Your Brain Healthy.