Life and Memory Center

I am often asked “What is the most important thing to do to help my brain?” The evidence seems clear to me. Physical exercise is the key. The results of several recent studies add to my confidence.

A prospective study of 700 elders (average age = 80) showed that vigorous exercise lowered the risk of development of Alzheimer’s disease and slowed cognitive decline. The study was a part of the Rush Memory and Aging Project. The prospective study (participants were enrolled and followed forward) was the first to objectively measure the amount of exercise rather than rely on self-report of amount of exercise. Data were analyzed after 3.5 years. The exercise effect was evident even after statistically adjusting for social activity, cognitive stimulation, depression, health, and APOE status (a “risk” gene for Alzheimer’s disease). But beware that the benefits of exercise were found when comparing the two extremes of low exercise (lowest 10%) and highest exercise (top 10%). Intensity and consistency of exercise are important.

Another recent study demonstrated that resistance training twice a week for six months and 12 months improved executive and memory function in women with Mild Cognitive Impairment (who are at risk for dementia). Furthermore, participants in the Exercise for Cognition and Everyday Living also showed that women 70 to 80 years old who participated in twice weekly resistance training showed improvement in executive function and memory. Although these studies are small in size, they add to the growing consistency of the benefits of exercise and suggest that both aerobic and resistance training are uniquely important for maximum benefits.

Finally, there is good news for those with Parkinson’s disease. Vigorous resistance training reduces the effects of the disease. Subjects in this study averaged 59 years old and had been diagnosed for an average of 7 years. Participants engaged in either resistance training or a traditional fitness program focusing on balance, flexibility, and strength. Weight training produced improved scores on a Parkinson’s rating scale. Apparently, challenge to the neuromuscular system improves function in Parkinson’s disease.

Overall, these findings are very encouraging. A rigorous exercise program improves both cognitive and motor function in neurological disease and may slow progression. Furthermore, there are unique benefits to resistance training. This is an aspect of your life where you have control and can be proactive. I aim for 40 minutes of aerobic training three times a week and resistance training twice a week.

Dementia comes in many forms and many stages. The term is so often used without a formal definition. Many confuse Alzheimer’s disease with dementia. The terms are not interchangeable. Dementia is a permanent and irreversible brain disorder that robs a person of independence. There are no current treatments that can reverse a dementia. There are no “pseudodementias.” If one is confused because of thyroid disorder or deficiency of vitamin B 12 and replacement makes the confusion go away, the person was not demented.

There are many possible causes of dementia. Dementia many arise from a stroke or a head injury. Dementia is often associated with Alzheimer’s disease, Lewy body disease, and Parkinson’s disease. A less common (estimates are at about 50000 in the United States) and often more challenging form of dementia is called frontotemporal dementia. Frontotemporal dementia is a progressive brain disorder that has at least major two subtypes: behavioral and language disorder. These disorders typically strike at a younger age, progress faster, and do not attack memory first as does Alzheimer’s disease.

The behavioral subtype is characterized by changes in personality. The afflicted person has decline in decision making, judgment, and reasoning. The person may lose inhibitions, and moral judgment. They make shop lift or have eating binges or other stereotyped or compulsive behavior like hording. They are apathetic and often socially inappropriate. There are often years of misdiagnosis ranging from midlife crisis, stroke, or psychiatric disorder (e.g., depression, bipolar disorder, anxiety disorder, PTSD, psychopathic personality).

The language subtype of frontotemporal dementia is often called primary progressive aphasia. It is characterized by struggling to get words out. As the disorder progresses speech becomes more halting and finally either mutism or a form of babbling appears. The afflicted person, in the early stage, often knows what they want to say but cannot find the word. As it progresses speech becomes less and less fluent but memory is not as much of an issue as not being able to say what one wants to say.

The first cases of frontotemporal dementia were described by Arnold Pick and hence were called “Pick’s disease.” Now these disorders are called frontotemporal dementia or FTD for short. Frontotemporal dementia often looks very similar to what we call Alzheimer’s disease in its middle to late stages – as do most progressive dementing disorders. Frontotemporal dementia often appears in the 50s and survival averages about 8 years.

There are no currently approved medical treatments for frontotemporal dementias. They are occasionally associated with bursts of poorly understood creativity. The most effective interventions are aimed at the caregivers who must manage through the years of misdiagnosis and progressive deterioration at a comparatively young age.

Last week I discussed my concerns about using biomarkers and brain scans to diagnose Alzheimer’s disease. This week Medscape (www.medscape .com) published an article that suggested that “misdiagnosis of Alzheimer’s disease [in about two thirds of participants] based on positron emission tomography scan readings appears to be a troubling problem that could get worse as more amyloid-specific tracers become available.”

This is the first study to my knowledge to present objective evidence suggesting caution about the use of brain scans to make a diagnosis of Alzheimer’s disease. The unique thing about this study was that the scans were done on community dwelling participants (mean age of about 64 years). Studies used to make the case for the accuracy of scans have so far only used highly selected participants – a sampling bias that distorts results.

The bottom line is that positive scans detect high levels of amyloids but high levels of amyloids don’t mean that the person scanned has Alzheimer’s disease. Indeed, another article (Archives of Neurology, April 23, 2012) presents data that both amyloid (associated with plaques) and tau (associated with tangles) proteins need to be present for cognitive decline. Decline over a period of three years was not associated with high levels of amyloid proteins in cerebrospinal fluid (CSF). Rather decline after was associated with high levels of both tau and amyloid proteins in CSF.

What this means is that scans are still research tools and not diagnostic tools for Alzheimer’s disease. In everyday clinical practice, scans should not be used for diagnosis of Alzheimer’s disease. Instead, diagnosis needs to be made on the basis of careful and detailed history/course, neurological exam, neuropsychological exam, and structural imaging. Furthermore, diagnose often requires serial assessments with the first exam as a baseline. Eliminating any of these steps dramatically increases misdiagnosis and increases unneeded stress.

Donepezil, generic name for Aricept, (and presumably rivastigmine and galantamine) and Namenda were associated with less decline over the course of one year than when both medications were discontinued in patients with moderate to severe Alzheimer’s disease. Adding Namenda was no more effective than treatment with donepezil alone.

An article in the British Medical Journal (March 22, 2012) warns that the 23 mg dose of Aricept is associated with more nausea and vomiting than the 10 mg dose. These effects can lead to serious medical problems. Drs. Schwartz and Woloshin claim that the label for the higher dose is misleading as there is no evidence of clear benefits from the higher dose when compared to the standard dose of 10 mg. They have petitioned the FDA for review.

I recently received a question about whether I stand by my concerns over the new criteria for diagnosing Alzheimer’s disease (original article from April 2011). The short answer is yes. Alzheimer’s disease presents in three broad ways. The first is an early stage where there are no obvious symptoms but changes are already occurring in the brain. This is the stage targeted by the new diagnostic criteria. The idea is that the failure of treatments in clinical trials to date is that we wait too long to start taking the drugs as the brain is too damaged to benefit.

Successful treatment would delay or prevent progression to the next stage called Mild Cognitive Impairment where the problems are mild and there is no disability. Dementia is the third phase where changes are severe enough to cause loss of independence and disability.

The early phase is identified by the use of biomarkers such as brain scans and tests of cerebral spinal fluid are used to identify the early stages of Alzheimer’s disease and to start treatments. There are several serious flaws with this strategy. First, diagnosis would be made on the basis of amyloid proteins which are associated with the development of plaques – a theory of what causes Alzheimer’s disease. However, autopsy studies, up to 30% of people with dense amyloid plaques never develop clinical signs of Alzheimer’s disease. They would be misdiagnosed. Second, the most advanced clinical trial of amyloid reversing drugs was terminated by Lily last year. The drug reversed amyloid deposition but clients got worse rather than better. Third, how early should interventions start? Fourth, how safe is early intervention? Will there be unintended and damaging side effects of altering brain chemistry so early in life?

Furthermore, how will those with no clinical changes react to being given such a scary diagnosis? I have already had a number of clients who have seen me in a state of panic as a result of misdiagnosis and over diagnosis. They were living their life as if they would soon be demented and giving up when there is no need. Alzheimer’s disease is diagnosed by its course over time (usually many years). Not everyone who has memory decline will develop Alzheimer’s disease. Not everyone who has Alzheimer’s disease (or develops plaques) will become demented. Not everyone who becomes demented has Alzheimer’s disease

Reducing Alzheimer’s disease to molecular biology adds to the sense of fear and futility. We sit and wait for a medical cure. We already have excellent cognitive and memory tests that are not invasive and allow us to assess and monitor brain function just as we use blood tests to determine the functioning of thyroid, kidney, and liver. These tests are the gold standard but many in the medical community ignore their utility in diagnosis and tracking. Memory testing allows us to be proactive without inducing needless panic and hopelessness.
We would be better off putting more money and resources into life style interventions targeting middle life or earlier. For now, be proactive about your memory and protect your future. There is so much that can be done if the focus is on memory rather than Alzheimer’s disease.

The question that I have been confronted by this week is how I know if memory slips are normal for my age or signs of memory loss. This question is central to boomers as they approach aging. As you age you expect to change. You can’t run as fast. You can’t burn the candle at both ends as long as you used to. On the other hand, you know more, you are better at solving problems. Your brain will shrink (starts at 20 so not a big deal). Is it any wonder that you have small changes in the efficiency of your memory – senior moments?

Mental and memory skills show up in predictable ways as we age but we do not normally lose our memory. Normal aging is associated with slower thinking and inefficient multi-tasking – working memory. This is the memory system that allows you to do mental arithmetic, remember to take your wallet with you, monitor whether you just took your medications or turned down the thermostat. This and sluggish word finding are normal as we age and changes probably start in your 40s.

When I perform a memory assessment, I look for a number of changes that indicate that more is going on than normal aging. Among the things that I ask are:

Are you repetitive?
Do you have trouble remembering recent conversations?
Do you have trouble remembering appointments?
Do you frequently misplace objects?
Do you have trouble managing your medications?
Do you have trouble discussing current events or areas of interest?
Do you have trouble following a complex train of thought?
Do you have trouble performing tasks that require many steps (e.g., balancing a
checkbook, cooking a meal)?
Do you have trouble doing calculations?
Do you show uncharacteristic disregard for rules of social conduct?
Do you have trouble finding your way around familiar or unfamiliar places?
Do you have increasing difficulty finding words to express what you want to say?
Do you have changes in personality?
Are you more passive and less responsive?
Does a family member express concerns?
Are you worried about your memory?

If you or someone who knows you well expresses several (more than two) of these concerns, the changes may be more than simple aging. There are a myriad of possible causes that need to be explored by means of a thorough memory evaluation. There is treatment if you confront changes early. Your wellness program should include proactive memory assessment as well as routine medical tests. Your life plan should include at the very least following the one minute rule (anything given less than one minute of thought will fade from your memory), exercise, eat predominantly a “Mediterranean diet”, be social, and stay engaged with your interests and passions.

An interesting article was published in the British Medical Journal (April, 2012). Based on recent data from the Framingham Heart Study, survivors of malignant cancers have a lower risk of developing Alzheimer’s disease and those with Alzheimer’s disease have a lower risk of cancer.

The Framingham Heart Study is a longitudinal study began in 1948 with over 5,000 participants ranging in age from 28-62. A second phase of the study enrolled children of the original participants beginning in 1971. A subset of these groups (who were not demented) was followed for 10 years to provide the data for this study.

The cancer survivors had 33% less risk of developing Alzheimer’s disease than comparison subjects who never had cancer. Interestingly, survivors of smoking related cancers were less likely to develop Alzheimer’s disease than survivors of nonsmoking related cancers – however, they had a substantially higher risk for having a stroke.

Furthermore, having Alzheimer’s disease reduced the risk of being diagnosed with cancer. Of course, this side of the equation may be a result of under reporting cancer symptoms in those already diagnosed with Alzheimer’s disease. However, two studies demonstrated decreased incidence of cancer upon autopsy of deceased Alzheimer’s patients. Further, Japanese survivors of the atomic bombs who were diagnosed with Alzheimer’s disease had a substantially lower incidence of cancer but those diagnosed with vascular dementia had a greater incidence of cancer.

Two other prospective studies have produced the same pattern of reduced risk in cancer survivors when studying the association of cancer with Alzheimer’s disease. The same pattern of findings is also found for those diagnosed with Parkinson’s disease indicating that the correlation is not unique to Alzheimer’s disease.

Explanations of these intriguing findings are scarce. There may be some biological mechanism that links neurodegenerative diseases with cancer. Maybe some treatments, chemotherapy and radiation, for cancer may have a protective effect against neurodegeneration – despite their negative impact on cognition. These are very interesting data in need of explanation in future research as long as we don’t get so bogged down with preserving the amyloid hypothesis that we ignore other potentially useful directions.

Last week, I discussed the latest on intranasal insulin and Alzheimer’s disease. In mid February, I mentioned in passing that I was asked about coconut oil as a treatment for Alzheimer’s disease. Since then I have been besieged by questions about coconut oil. Bizarrely, the two articles converge. Let me try to provide a reasoned response to whether to try coconut oil as a treatment for neurological disease.

The idea of using coconut oil to treat Alzheimer’s disease gained popular attention through Alzheimer’s Disease: What if There Was a Cure: The Story of Ketones a recent book written by Dr. Mary Newport. The book is an extended case study of Dr. Newport’s husband. She was frustrated with current treatments and theorized that the problem behind Alzheimer’s disease was that brain cells were starved for glucose.
This is the same mechanism that makes intranasal insulin a potential treatment. In short, Alzheimer’s disease may be a “brain form of diabetes.” The hope is that insulin therapy may improve cognition, especially if started early enough (what constitutes “early enough” is still vague and undefined).

Dr. Newport theorized that as the brain is being deprived of its primary energy source, glucose, that ketones, an alternative energy source, could be used to fix the problem. Enter coconut oil. Coconut oil (or palm kernel oil) provides a dietary source of ketones.and may, therefore, be used to treat Alzheimer’s disease. She tried her theory with her husband. Her husband was diagnosed with Alzheimer’s disease in his early 50s and she was disappointed with available treatments. She gave him 20 grams of coconut oil twice a day and observed remarkable improvement over the next year. One source states that “the dementia continued to reverse itself.” It bears emphasis that this is a study of one person.

The bottom line is that this is a remarkable case study. The only downside I can find is that coconut oil as found in the grocery store is a highly saturated oil – like butter. This raises concerns about heart disease and stroke. However, some supermarkets and health food stores sell virgin coconut oil which has no trans fats.

In my opinion, this is a lot of theory but with no real evidence. Although the case study suggests a direction for research, both treatment with ketones and intranasal insulin need to be explored in rigorous clinical trials before we know whether they will prove to be effective treatments for neurological disease and whether there are so far undiscovered side effects. Until then be careful of the intensive marketing campaigns. Take supplements, including coconut oil, only after consultation and evaluation by your physician.

Everyone wants a simple fix for their memory and health. If only you could take a supplement that “fixes brain wiring so you dramatically improve your memory.” If only you could take a supplement that “restores lost neurotransmitters for a steel-trap memory.” Marketing is clever and plays to our fears with a mix of a few findings from tangentially related studies, “miracle memory molecules,” or “guarantees of your money back.” There are no short cuts. It takes time and effort to remain healthy. The latest Mayo Clinic Health Letter (March 2012) puts vitamin supplements in objective perspective without selling anything.

Their review of well conducted research concludes that many vitamins and minerals that we used to think prevented diseases may not help after all. Furthermore, there are small but consistent findings that vitamins and supplements may cause harm – even use of a multivitamin in those who are well nourished may slightly increase the risk of premature death. Before taking vitamins and minerals without consulting with your physician consider these findings.

Vitamin E – taking more than 400 IUs (maybe even as low as 150 IUs) may pose health risks including premature death. A large trial showed that vitamin E and selenium did not reduce the risk of prostate cancer as many had believed.

Vitamin A – may increase the risk of hip fracture in postmenopausal women. High doses of vitamin A are potentially toxic.

Folic acid (vitamin B-9) – supplementation of folic acid may increase the risk of premature death.

Vitamin B-6 – doses of greater than 100 mgs can cause nerve damage.

Vitamin B-3 (niacin) – high doses can lower cholesterol but may also damage the liver.

Iron – remember the Geritol commercials? Iron deficiency is rare.

You get the point. Vitamins and supplements need to be given after consultation and evaluation by your physician. He or she can advise based on your needs (tested objectively) and inform you which supplements to take and in what dose. Don’t rely on advertising or marketing claims. For example, up to 15% of older adults may be deficient in vitamin B-12 which creates problems such pernicious anemia and memory loss. Finding out if you need supplementation is simple. Your physician can order a blood test.

In sum, don’t prescribe for yourself. When it comes to vitamins and supplements there are risks. Take supplements only after consultation and evaluation. More is not better. Many vitamins and supplements are needed within a narrow range of concentration and both too little and too much can be harmful. The best current advice for those who want to focus on wellness is to eat a healthy diet such as a Mediterranean diet heavy with fruits, vegetables, and fish. Additionally, exercise consistently and be social. In the long run your body will take care of its needs if you follow this plan.

I am often confronted by questions about whether to take cholinesterase inhibitors such as Aricept, Exelon, or Razadyne. Anyone with a diagnosis of Alzheimer’s disease is better off taking one of these medications (it may not matter which one based on limited studies that directly compare these drugs) – if they tolerate them. The most troublesome early side effects are gastrointestinal, neuromuscular, and vivid dreams. Longer term use may slow heart rate and cause fainting.

There are studies demonstrating the effectiveness of these medications in all stages of Alzheimer’s disease from mild to severe. For example, I conducted a study a few years ago on the effect of Aricept on total score on the Dementia Rating Scale. The Dementia Rating Scale provides an objective measure of severity of cognitive decline. A perfect score is 144 points and we should all be able to score above 140. A score of 123 or below is consistent with a diagnosis of dementia. Scores were obtained from both participants who could tolerate the drug and those who couldn’t. Whereas those who could not tolerate the medication showed decline in scores 9-12 months later, those who tolerated the drug showed an average improvement of about 6 points.

Aricept was shown to have a positive effect on residents with severe Alzheimer’s disease in skilled nursing facilities. A special test, the Severe Impairment Battery, was necessary in that these residents were too impaired to complete a meaningful Dementia Rating Scale. Furthermore, treating these residents with both Aricept and Namenda improved scores more than either medication alone.

I am also asked about how long to take the medications. This is a very complex question to answer. Part of the problem is that Alzheimer’s disease is progressive and gets worse over time. This leads to the inference that the medications quit working. To this point, there is both empirical and clinical data showing that there is a risk for more rapid decline in those who stop taking the medication. Current medications slow the decline; they do not reverse the disorder.

A study published March 8 (The New England Journal of Medicine, 2012) demonstrated that Aricept and Namenda both improved scores on testing as well as improved ratings by observers. The unique aspect of this trial was that participants (with moderate to severe Alzheimer’s disease) still resided in the community and were already on Aricept. Those who continued with the drug scored higher than participants who were taken off Aricept 52 weeks later. Those who switched to Namenda were also better than those switched to a placebo. In this study, the combination of Aricept and Namenda was no better than either alone.

In short, cholinesterase inhibitors help many with Alzheimer’s disease do better over time. Furthermore, once Aricept is started (presumably this also applies to the other cholinesterase inhibitors), it should be continued unless there is a compelling reason to stop. The effect is not large but it appears to be consistent in those who tolerate it.

I was asked an interesting question during my last workshop. To paraphrase, “I go to my doctor and complain of anxiety, depression, memory …. Often, he or she gives me a prescription and reassures me that I will do better. What if I don’t want to take a medication? Is that my only choice?” Fortunately the answer is no.

We live in a reductionist world. Biological interventions such as medications are helpful for many problems. Drugs change physiological systems. But behavioral and psychological interventions also change physiological systems. When I learn something new, I alter my brain. When I exercise, I alter my biology. We often lose sight of the fact that biology changes behavior and behavior changes biology. The best interventions focus on both sides of this equation.

For example, there are medications that help manage changes in motor function (e.g., reduced length of stride and postural stability which increases falls) in Parkinson’s disease. A new study (New England Journal of Medicine, February 9, 2012) confirms the growing evidence that training in Tai Chi improves balance and reduces falls in patients with Parkinson’s disease – think of what it might do to help the rest of us as we age and become more at risk of falling. The program only required 2 times a week for 24 weeks to show the improvement. Changes in behavior changed biology.

As another example, consider yoga training (thanks to Jane Brody’s article in the New York Times, February 21, 2012 in response to reading The Science of Yoga by William J. Broad). She reports that well designed studies have shown that the regular practice of yoga can improve cardiovascular variables (effects the heart and brain) such as blood pressure, blood sugar, cholesterol, and improve blood levels of antioxidants. Yoga also improves balance and may reduce the risk of falls (maybe Tai chi does more than just improve balance). Changes in behavior changed biology.

Finally, as you have read or heard me say often, you can improve your memory by changing your behaviors. The One Minute Rule – anything given less than one minute of thought will fade from your memory – involves changes in behavior that change physiology such as building the habit (a type of long-term memory that involves neuroplasticity) like training yourself to have a “take away spot” for your wallet, keys, and grocery list. The one minute rule allows biological processes of memory formation to have more time to work their magic.

In short, medications are not the only approach to change biology. Behaviors such as exercise, eating habits, memory habits, cognitive stimulation, and being social also change biology. Medications are not the only or always the best ways to improve the quality of our life.