Life and Memory Center

In 2004 the best available research indicated that supplementation with vitamin E slowed Alzheimer’s disease.  A major clinical trial at the time indicated that taking 2000 IU of vitamin E per day delayed placement in care facilities by several months compared to placebo.  By the way, treatment with selegiline (a type of antidepressant) produced the same effect.  Another study at the time demonstrated that eating a diet high in vitamin E was correlated with higher mental function in men and women aged 65 – 100.  Hence, many were taking high doses of vitamin E and supplementation was the standard of care for Alzheimer’s disease.

However, there were concerns regarding such a high dose of vitamin E as it produced side effects such as potentiating the effects of anticoagulants such as aspirin and Coumadin and increasing bruising and risk of bleeding.  There was also evidence that doses above 1500 IU suppressed immune function as suggested by a study in the Netherlands showing slower resolution of upper respiratory infections in institutionalized elderly.  Other studies at the time (Annals of Internal Medicine, 2005, 142,37-46) indicated that supplementation with vitamin E did not reduce the risk of cancer or major cardiovascular events but did increase the risk of heart failure and mortality.   Finally, treatment did not alter the course on Mild Cognitive Impairment “converting” to Alzheimer’s disease.

Hence, the recommendation was that generally using more than 400 IU of vitamin E was not prudent because the risks were too high.

Fortunately research continued.  The most recent clinical trial of vitamin E showed that treatment of those with mild to moderate Alzheimer’s disease slowed functional decline in activities in daily living (“High-dose vitamin E slowed the decline of people with mild and moderate Alzheimer’s disease,  Journal of the American Medical Association, 2014, 11, 29-30, 33-44).

The study was conducted at 14 VA medical Centers on 613 mostly male participants.  Participants were randomly assigned to receive Vitamin E (20000 IU per day), Namenda, vitamin plus Namenda, or placebo treatments.  Nearly all (97%) were treated with either donepezil or galantamine before and during the study and diagnosed with mild to moderate Alzheimer’s disease.  Over the course of 2.3 years those treated with vitamin E had less functional decline.  Namenda had no effect and, surprisingly, the combination of Namenda and vitamin E had no effect.  There was no increase in mortality as a result of treatment with this high dose of vitamin E.

In short, treatment with high dose vitamin E was effective and did not appear to cause harm.  On the other hand, treatment with Namenda did not have an effect and treatment with Namenda and vitamin E cancelled the benefits. None of the treatments delayed cognitive decline.  Vitamin E or Namenda have no preventative action for those without memory symptoms or for those with Mild Cognitive Impairment.  Apparently the stage of Alzheimer’s disease is an important factor in treatment that is only beginning to be understood.

Don’t forget to monitor your memory.  I have developed a focused, thorough short-term memory assessment that is brief and affordable.  Contact my office for details if you want to check out your memory.

Depression is not part of normal aging and is one of the most common, treatable problems in older adults.  Depression in older adults is under-recognized and undertreated.  It may impair independence and make health problems worse.

 The symptoms of depression include:

• Depressed mood most of the time
• Loss of interest or pleasure
• Disturbed sleep (too much or too little)
• Weight loss or gain
• Fatigue or loss of energy
• Feelings of worthlessness or guilt
• Difficulty in concentration
• Difficulty in decision making
• Restlessness or agitation
• Frequent thoughts of death or suicide

There are three basic types of depression.  Major depressive disorder is characterized by having 5 or more of the above symptoms nearly all the time for at least two weeks.  Often those with major depression feel hopeless, anxious, worry, and loss of pleasure.  Minor depression is characterized by having 2-4 of the above symptoms nearly all of the time for at least two weeks.  Despite calling it “minor” it is not trivial and responds to treatment.  Dysthymia is a “minor” depression that is chronic, occurs most of the time for at least two years.

Whereas about 5% of older adults living independently suffer from major depression, as many as 26% experience minor depression or dysthymia.  These numbers increase to 15% and 35% for those in skilled nursing homes.  Left untreated depressive symptoms are persistent.  Estimates suggest that 60-80% of older adults who receive appropriate treatment will become less depressed and have a higher quality of life.

Effective treatment of depression must address issues of health as well as mood.  Issues such as diabetes, heart disease, arthritis, and hypertension increase the risk of depression and must also be addressed.  Anxiety often co-occurs with depression and adds to the distress.   Furthermore, cognitive impairment may accompany depression and complicates treatment.  Caregiving for someone with cognitive as well as physical disorders often leads to depression and anxiety and must be addressed.

A large component of treating depression is re-engagement.  Treatment works best when it involves a return to meaningful activities.   This is often the crux of treatment as those who are depressed don’t want to exercise, be social, or go to activities.  Treating depression requires getting moving despite the lack of interest or energy.

Psychotherapy for depression is effective as and may be even more effective than medications for minor depression.  Short-term cognitive behavioral treatment or problem-solving therapy may be particularly helpful.   If you are someone you care for suffers from depression, don’t go it alone.  A course of brief therapy can restore your quality of life.

Have you ever hunted for your car?  Keys?  Glasses?  Have you ever left home without your grocery list?  Have you ever had a senior moment?  How do you know if it is a sign of future memory loss?  Do you live with or care for someone who is forgetful or has memory loss?  If so, this workshop will help.  Remembering what not to forget is designed for baby boomers, older adults, and caregivers of those with mild to moderate memory loss.  After completing the workshop, you will have practical and ready to use strategies for improving memory and protecting your future.

You will learn:

• How memory works.  The difference between long-term and short-term memory.
• How memory normally changes as we age.
• How to tell the difference between normal aging and memory loss.  Stages of change so you can be proactive about your future.
• Strategies for improving memory as you age. What life style changes help and which do not.  How to plan and manage legal and financial strategies.

Initially, I was excited to see a review article titled, “Efficacy and safety of cognitive enhancers for patients with mild cognitive impairment: a systematic review and meta-analysis” (Canadian Medical Association Journal, 2013, September 16).   However, I was disappointed after carefully reading the paper.  I had hoped to gain insight into whether cognitive enhancing medications (Aricept/donepezil, Exelon/rivastigmine, and Razadyne/galantamine – there were no cognitive data for Namenda) help those with Mild Cognitive Impairment but there are too few studies with too many limitations to get a clear answer to the question of benefits.

Mild Cognitive Impairment is usually characterized by mild memory/cognitive deficits in those without functional decline in everyday skills.  These are persons who do not meet the criteria for Alzheimer’s disease but are clearly at greater risk of obtaining the diagnosis in the future.  The question is whether treating such individuals with one of the cognitive enhancers changes their clinical course.

The findings from the review are fairly clear.

1. There was a beneficial effect of treatment with cognitive enhancers between 12-84 weeks.  There was no difference between treated groups and placebo between 85-96 weeks.
2. There was no difference in efficacy between the medications (e.g., donepezil vs. galantamine) despite different mechanisms of action.
3. Treatment did not alter functional outcome when compared to placebo.
4. There was no benefit from these medications when compared to placebo for treating behavioral/psychiatric symptoms.
5. There was no increase in mortality for those taking these medications up to 156 weeks.
6. Nausea, diarrhea, and vomiting were significant side effects compared to placebo.

The problem is that there are too few studies (eight) to generate reliable conclusions and the studies were not well designed or well reported.  Furthermore, the studies were too short in duration.  The “conversion” from Mild Cognitive Impairment to Alzheimer’s disease takes many years and the longest studies were too short.  There was inconsistent definition of Mild Cognitive Impairment.

In short, I was hoping to gain clear guidance on whether treatment with Aricept/donepezil, Exelon/rivastigmine, or Razadyne/galantamine provides benefits for those with Mild Cognitive Impairment.  After reading the review, I am dismayed with how few resources we have put into resolving this important treatment issue.  The best guidance I can give is that there appear to be mild long-term benefits for those who with Alzheimer’s disease who tolerate these medications.  The question of how early to start treatment is still open.

One of the most important yet difficult issues we all face with the proliferation of medications available and in development of new drugs, especially those affecting the central nervous system, is how to determine what is a meaningful drug effect.  How does one know which drugs are effective and which are not?  What is a meaningful treatment effect?  How do professionals decide which drugs to recommend?  Are newly available drugs better than older medications?

We rely on large studies called randomized clinical trials (RTCs) to answer these questions.  RTCs are scientifically rigorous studies designed to evaluate the safety and efficacy of medications (often compared to a placebo). The problem comes when we try to interpret the findings from these studies.  What constitutes a meaningful result depends upon whom you ask (Defining a clinically meaningful effect for the design and implementation of randomized control trials, Innovations in Clinical Neuroscience, 2013, 10, 4S-19S).

The issue from the clinicians’ and researchers’ perspective is actually simple.   The drug in question must be “significantly” better than the placebo or comparative medication.  The concept of what is significant is based on well-accepted decision rules from standardized statistical design and analysis.  The concept of statistical significance is derived from defining a priori the risk of making the mistake of saying that two drugs differ in effectiveness when in reality they do not.

The complication is that a treatment effect may be significantly different from a placebo but trivial and therefore not meaningful. This is especially true of many of today’s studies that rely on huge samples sizes.  For example, a well-designed study with a large sample, say 10,000 patients, will facilitate discovery of statistically significant results that may be trivial. The definition of meaningful is elusive and depends on whom you ask.

The perspective of who pays for the medication.   Representatives from the federal government and insurers define meaningful effects based on what medications should be covered.  Payers are not impressed with mechanisms of action, new pathways, or meeting unmet needs.   They define meaningful based on cost and economic value.

The perspective of investors.  Quit simply investors define meaningful in terms of how many people are willing to buy the new drug.

The perspective of the FDA.  Approval is a complex decision process based on “substantial” evidence. There are no definitions, regulations, or universal agreements for defining what constitutes substantial evidence.

The perspective of the patient.  The patient’s perspective on meaningful is the most neglected aspect of this formula.  Patients participate in clinical trials under the assumption that the study is designed to determine the most beneficial treatment, which is not the objective of an RTC.  The drug consumer defines beneficial based on the treatment’s ability to improve their quality of life without doing harm.

In short, there is no consensus of how to determine meaningful treatment effects.  This is a complex issue that I have thought about for years.  I still don’t know how to best answer the question of meaningful treatments.  My hope is that we do a better job in the future of finding a way to incorporate the person into future formulas.

There are a multitude of risk factors for Alzheimer’s disease.  As I have often written, the best treatments are proactive rather than reactive.  Risk factors help you be aware that you need to evaluate and monitor your memory and incorporate external memory supports, strategic planning, and life style enhancements to better protect your future.

Age is the clearest risk factor for a diagnosis of Alzheimer’s disease.  Age trumps all other factors.  Most of those diagnosed with Alzheimer’s disease are 65 and older.  The risk reaches nearly 50%by age 85.  Anyone over the age of 65 should consider a thorough memory evaluation to establish a baseline.

Genetics.  If you have a first-degree relative (parents or siblings) with Alzheimer’s disease, your risk is about 3-4 times that of those who do not have a first-degree relative.  But the genetics are complex and unclear.  Genetic testing is not currently reliable enough to pursue.  Positive outcomes may cause needless emotional distress.

Head trauma.  There is a strong link between head trauma – especially serious and repeated – and Alzheimer’s disease.  Buckle your seatbelt and wear a helmet for sports and motorcycle riding.

Heart disease increases the risk for dementia.  Aggressively manage blood pressure and heart risk factors and maintain good physical conditioning (aim at 2.5 hours of at least moderate exercise per week).  Don’t smoke.  Moreover, recent research suggests that the combination of smoking and heavy drinking (more than two alcoholic beverages per day) accelerates cognitive decline (British Journal of Psychiatry, July 11, 2013).

Diabetes.  Many have suggested that Alzheimer’s disease may reflect a “type 3” diabetes in the brain.  This is an active direction for current and future research and indicates that you can manage this risk by diligent monitoring for diabetes, eating a healthy diet, and exercising.  Indeed, recent research has suggested a link between high blood glucose (115) and increased dementia even in those who do not meet the criteria for diabetes (New England Journal of Medicine, August 08, 2013).

Depression.  Depression, especially in mid-life or latter is a risk factor for Alzheimer’s disease.  There is no evidence of which I am aware of the effects of treating the depression on future risk.

Behaviors during adolescence.  A new study suggests that “young onset dementia” (before age 65) in men is associated with alcohol intoxication/abuse, stroke, depression, use of antipsychotic medications, dementia in father, drug use, and high systolic blood pressure, low cognitive function, and low height (JAMA Internal Medicine, August 12, 2013).  The risk is greater when 2 or more of these factors are found together.  I assume that at least some of the factors are relevant also for women and influence cognition in those over 65.   This finding is interesting as it suggests that life style interventions can never start too early.

Why do we need a new diagnostic category of “subjective cognitive decline?”  We already have a system in place to stage the level of memory loss and concerns.  The challenge of a slowly progressive disease like Alzheimer’s is that it unfolds over several decades, it has subtle beginnings (difficult to tell from senior moments early on), and it does not always lead to dementia (i.e., disability).  This means that many, but not all, will be aware that they are changing well before it can be recognized from the outside.

The Global Deterioration Scale is designed to stage level of memory loss and has been available for years.  It comes in several forms but in essence the scale marks seven stages from no decline to total disability.  It serves as a guide to determine what actions need to be taken and what level of caregiving is required.  The stages are as follows:

Stage 1: Normal.  No obvious memory deficits on either interview or objective assessment beyond normal aging.  May be marked by subjective complaints that should be monitored by serial memory assessments.

Stage 2: Forgetfulness.  Often manifested by subjective complaints about forgetting or not as “sharp” as in the past but no obvious memory deficits on either interview or objective assessment.  If prior thorough memory testings, score has declined compared to baseline. Memory screenings at this level are not helpful as they are too easy

Stage 3: Early Confusional State. Marks earliest clear-cut deficits on interview and objective testing.  Slowness in doing complex tasks and often less able to organize things.   Memory Screenings may show mild changes.

Stage 4: Late Confusional State.  Very clear-cut deficits on both thorough objective testing and clinical interview.   Instrumental activities of daily living (IADLs) such as handling finances, doing the checkbook, cooking is impaired.  Memory Screenings show mild changes.  Needs assistance with complex tasks.

Stage 5: Early Dementia.  Person so impaired that they would no longer survive without some assistance.  Cannot live alone.  Needs caregiving for meals, managing medications, shopping.  Forgetful of major facts about personal life.  Personal care still intact.  Memory Screenings show moderate changes.

Stage 6:  Middle Dementia.  Severe impairment on both interview and objective assessment.  Unaware of surroundings.  Needs assistance with activities of daily living (ADLs) such as toileting, bathing, may be incontinent, cannot travel alone.  Very passive as a rule and disengaged.  Difficulty with communication.   Needs 24/7 supervision.  May do very well in secured, structured memory are units.

Stage 7: End Stage or Terminal Dementia.  Very severe cognitive decline.  Cannot talk, cannot dress, incontinent, bedbound, needs to be fed.  Consider hospice as part of the care plan.

Strategic planning starting in stage one is essential for effective treatment of progressive memory loss.  Your best protection comes from monitoring stages and proactively planning ahead for how to manage changes before they occur.  The best plans get on top of things before the person forgets that they forget.

I have had a number of clients over the years that have come to me with concerns about their memory that seemed just fine.  For example, there was the 82-year-old woman who was a Smith College graduate in physics.  I evaluated her four times over the course of ten years.   On the first evaluation, she tested among the highest I have ever seen – including short-term memory.  However, on each of four subsequent evaluations, her short-term memory scores declined even though the word list was the same.  She obviously was aware of changes before testing could detect decline.

Clients such as this are referred to as the “worried well.”  Professionals dismiss them as if they are not aware of their own bodies.  I find this particularly disturbing as progressive neurological conditions such as Multiple Sclerosis, Parkinson’s disease, and Alzheimer’s disease are often misdiagnosed as psychiatric conditions early on and self-perceived symptoms are dismissed.  As well reviewed by Pam Belluck in the New York Times (Dementia’s signs may come early, July 18) new data have begun to alter thinking about such complaints.  Apparently people with concerns about memory and organizing skills are more likely to have abnormal amyloids – a correlate of Alzheimer’s disease – than those without such complaints.

Those who sense that their memory skills are declining are now identified by a new category called “subjective cognitive decline.”   Finally professionals are saying “Hey, maybe there is something to this, and maybe we should pay attention to these people” (Dr. Ron Peterson as quoted by Pam Belluck).

Unfortunately, “experts” are not recommending evaluating for subjective cognitive decline because of the mistaken belief that there is no effective treatment – “there is nothing you can do.”  But subjective changes mark opportunity.  Clearly, not everyone with such complaints will decline or become demented.   The best treatment for possible progressive memory loss is to intervene early.  Treatment involves building memory skills and strategic planning to insure a better future just as you have already done by creating a financial plan before you needed the money.  Subjective worries should be assessed  routinely and thoroughly as part of monitoring wellness.

The goal of successful aging is to have as good a life as possible.  This is true whether your memory holds or declines.  The best way to assure that you will do the best you can is to be proactive.  Strategic planning for the future is essential.  There is lots of time as memory loss progresses very slowly.  Don’t write off feelings that your memory is declining.  Get a thorough memory evaluation.  Put together an advisory team that includes at least an attorney, a physician, a financial advisor, and a memory expert.  Include family members in the assessment and planning.   Treat memory loss by staying ahead of it.

Alzheimer’s disease unfolds over the course of decades.  Despite the intensive search, there are no accurate and reliable biological markers for Alzheimer’s disease.  Diagnosis is based on a combination of factors including details of course and history gathered from the person who has memory loss as well as family and/or friends.   There must also be a medical work up searching for treatable causes of memory loss such as thyroid function, status of diabetes, anemia, and imaging studies.  The standard of care also requires cognitive evaluation to map out strengths and weaknesses and stage the disease.  Finally, diagnosis requires clinical judgment.

There is a push for a new set of criteria that diagnoses Alzheimer’s disease into three stages and is based on the fact that Alzheimer’s disease begins well before symptoms emerge (Practical Neurology, 2013, March/April, 34-35)).  The first stage is the preclinical stage.   This is the stage before symptoms and before memory loss appears.   It is founded on finding measurable changes in the brain, cerebrospinal fluid, and/or blood.  These changes occur 20 or more years before symptoms.  The rub is that there are no guidelines on how to make this diagnosis and no biomarkers that are no generally accepted biomarkers for making this diagnosis.  It seems to me that this is like arresting someone before they commit the crime you think they will commit.

Mild cognitive impairment is the second stage.  This stage is mild (the afflicted person can still function in daily life) yet there are measureable changes in memory that are noticeable to family and friends.  The latest estimate is that 10-20% of those over 65 have mild cognitive impairment. There are subtypes of mild cognitive impairment and those forms accompanied by memory loss are the most likely to decline.  Some with mild cognitive impairment decline whereas others do not.  There is no known reason for this difference.  If accurate biomarkers become available, those with mild cognitive impairment and positive markers will be reclassified as mild cognitive impairment due to Alzheimer’s disease.

Dementia due to Alzheimer’s disease is the third and final stage.  Independence is lost as the symptoms interfere with daily life.  This stage is where Alzheimer’s disease is diagnosed currently.

Are these criteria an improvement over what we use now?  The intent is to develop treatments that delay or modify Alzheimer’s disease before it produces symptoms.  But there are no good criteria yet for stage one and biomarkers are still research tools.  Do we really want to tell someone that they have Alzheimer’s disease when they have no symptoms and may not develop any?

What is the most useful way to enhance and protect my cognitive skills as I age?  Brain exercise products, “brain fitness computer programs,” have burgeoned over the last few years to the point that they have already become a $300 million industry.   The programs promise to improve memory, attention, and creativity.  They promise to prevent or delay Alzheimer’s disease and dementia.  The programs are heavy on marketing but lean on rigorous evaluation.  Are the programs worth the investment?  Is it better to work-face-to-face or to use a computer program?

In an attempt to answer these questions, I just read a complicated review article “Computerized cognitive training with older adults” (PLoS One, 2012, 7, e40588, 1-13).  The intent, in part, was to compare the efficacy of face-to-face cognitive training to computer based programs in healthy older adults (those over 50).  First, there are few good data to work from.  There were only 151 studies addressing the issues before July 2011 and only 38 of these were rigorous enough to be useful.  Second, the promise of slowing or preventing decline was not and has not been well addressed.

The actual cognitive benefits from the training were small.  Neither computer based program nor face-to-face training was clearly superior – both helped.  Training was often specific to the skill trained and often did not generalize either to other skills or to everyday life (a question not often or well addressed).  Computer programs and games have the advantages of instant feedback, cost, and convenience.  Face-to-face training provides the advantages of tutoring/mentoring strategies, socialization, and tailoring exercises to the individual.  Both types of training can be fun and engaging.

The decision of which way to go is driven more by taste and comfort with technology than proven empirical validation.  Either way, these training methods are similar to the older methods of memory training and mnemonics – remember Jerry Lucas and Dale Carnegie?

The main thing to remember is that the brain – even in those with mild cognitive decline -is very plastic and adaptive.  We live so much of our daily lives on long-term memory, routine, and habit.  It is only with advanced decline that these skills regress.  Much learning is unintentional and therefore living a meaningful engaged life will often let memory take care of itself as long as we don’t forget The One Minute Rule – anything given less than one minute of thought will fade from your memory.

There are multiple ways to “train” your brain.  We often learn by observing and imitating others.  We learn by practice and doing.  We learn by being read to or watching videos or movies.  We learn by solving problems.  We learn throughout life as long as our short-term memory holds well enough.

If computer games are interesting and fun for you, go ahead and do them.  But don’t forget that learning involves more than a computer program.  Learning is the ability to benefit from varied experiences.  It comes in a multitude of ways.