Life and Memory Center

The foundation of any cognitive wellness program consists of evaluation, long-term planning, and goal setting. Cognitive wellness also requires a lifelong commitment to exercise. In addition, cognitive wellness is further enhanced by managing short-term memory, remaining cognitively stimulated, and social.

Short-term memory failure is usually the culprit for senior moments as well as the first sign of diseases such as Alzheimer’s disease. Short-term memory is not a time but rather the process by which the brain learns new information such as a new name or a change of address.

There are two basic causes of forgetting involving short-term memory. First, you will not remember if you don’t pay adequate attention. New information does not get attended to well enough in situations like multi-tasking or stress and fatigue. This is like attention deficit disorder. Second, the short-term memory system in the brain weakens after a stroke, a head injury, or the development of progressive dementias such as Alzheimer’s disease.

The solution to fixing short-term memory is the One Minute Rule. Anything given less than one minute of thought will fade from your memory. That’s why we take notes, use Post-its, repeat names, and use reminder tones on cell phones. It’s the whole point of mnemonics. These are strategies that allow us to better attend to and to encode new information so we can remember it better in the future as short-term memory cannot be exercised. Once these strategies become habits, they protect us against weakening of short-term memory circuits in the brain. The trick for treating short-term memory loss is having the habits in place before you need them. With progressive short-term memory loss you live better as a result your habits, skills, and memory supports as you have to live more and more in the moment.

Long term memory consists of knowledge (the capital of Florida, the planets in the solar system), skills (swimming, using a microwave, playing Bridge, doing crossword puzzles), personal history (birth date, address, and social security number), habits (writing appointments in your calendar, brushing your teeth). Long-term memory is built through repetition and practice. It works like a muscle in that the more you work it the stronger it becomes. You build long term memory by engagement and stimulation (go to museums, use in “brain fitness” programs, reading, taking courses, attending concerts, etc).

In short, don’t just leave your memory or your future to chance. Plan on how you will remember. Plan to have a good life, even if you can’t remember it. Treating progressive dementia requires a long range plan that includes financial, legal, medical, and cognitive/memory components that are most effective if they are in place before you need them. Alzheimer’s disease unfolds over decades and responds well to early treatments that add quality to life whether your memory remains intact or declines as you age.

To review from last week, Alzheimer’s disease unfolds over a very long time which gives us an opportunity to develop a comprehensive wellness plan before changes set in. Everyone’s life plan should address the four pillars of long term wellness: advanced directives, financial planning, physical health, and cognitive/memory health. We are fairly good at long term commitment to the first three but many ignore the fourth pillar of wellness: memory and cognitive health.

The foundation of any wellness program is evaluation. Baseline evaluation allows measurement of strengths and weaknesses to allow for development of strategies for enhancing skills. Ongoing evaluations allow feedback on progress and needed refinements in long range goals. Finally, evaluation allows monitoring of changes. Memory evaluations should begin by at least age 50 for anyone with high risk for developing Alzheimer’s disease (e.g., family history, late life depression, head injury of memory loss). Assessments should begin by age 60 for those who do not have such risks as age is the greatest risk factor for development of Alzheimer’s disease.

Memory is assessed and monitored using a challenging learning task – learn a list of words. The list needs to challenge even those with normal memory to be effective. A good memory assessment consists of first learning something new (i.e., a list of words). Second, after learning the list to a preset level (say 5 rehearsals), you are distracted (i.e., given a different list to learn). Finally, you are asked to recall as many words as possible from the first list as measure of strength of short-term memory. Findings are then scored and interpreted (just like blood work) to determine if your memory is as strong as it’s supposed to be for age, sex, and education. The process is repeated over time (just like blood work) to monitor changes over time or to assess effectiveness of treatments (e.g., memory strategies, medications, exercise, mental stimulation).

The most neuroprotective behavior that you can do is to exercise. The formula is simple. Those who are well conditioned do better in their attempts to manage age related diseases such as Alzheimer’s disease, Parkinson/s disease, chronic pain, diabetes, etc. Exercise enhances physical health, reduces depression and anxiety, enhances cerebral blood flow, and increases brain volume. Exercise enhances academic performance in the young, aids stroke recovery, enhances memory and executive functioning, strengthens bones, and decreases risk of falls. Cognitive benefits are gained after as little at 3 months of consistent exercising. The greatest benefits are gained by more strenuous exercising (sessions most days of the week for more than 30 minutes at a time) that includes both strength training and aerobics.

More on developing a cognitive wellness program next week.

To review from last week, the brain changes associated with Alzheimer’s disease are found 25 years before onset of symptoms. This finding is based on longitudinal study of families with a particularly aggressive form of Alzheimer’s disease and can probably be extrapolated to the late onset form of the disease. Furthermore, memory decline starts 10 years before symptoms and current medical screening (the MMSE) does not detect changes until 5 years before symptoms. In short, Alzheimer’s disease unfolds over a very long time. It gives us opportunity to develop a comprehensive wellness plan.

What does this mean for me and for my clients? There is hope for better managing memory disorders such as Alzheimer’s disease. So often I hear “Why should I address memory issues as there is nothing I can do?” This adds to the feelings of hopelessness and fear. There is time to get a long range plan in place as long as we don’t wait for a diagnosis (which can only be made decades into the disease). The four pillars of long term wellness are advanced directives, financial planning, physical health, and cognitive/memory health.

First, consider advanced directives. These are legal documents that outline who will manage my medical and financial decisions should I become incompetent (e.g. from a stroke, from a brain injury in the future). The Living Will adds guidance to my family for end of life decisions such as whether I want a feeding tube, whether I want my life extended by artificial means if there is no hope for future quality of life. Many have these documents by mid life. I suggest to my clients that they add plans for monitoring skills such as driving and finances to the plans. These are protections we hope not to ever need but so much the worse for those we love if these plans are not in place.

Second, we also are proactive about finances. Most of us have long range saving and investment plans (e.g., social security, IRAs) for having money available when we wish to work less. We willingly seek financial and investment counselors to help us establish and monitor this plan usually when we are early in our work career. We add insurance to protect us against catastrophic loss of resources or add to our taking care of loved ones. Many even plan for and prepay funeral arrangements.

Third, we are proactive about our health. We seek out advice from our primary care physicians that help us avoid or better manage long term health and wellness. We monitor important body functions to allow early detection of changes before disease sets in or to find it early and manage the course better. For example, we monitor heart function through physicals and blood work, stress tests, heart scans. We monitor for cancer by physical exams, blood tests, and screenings such as colonoscopies. We monitor for chronic diseases such as diabetes and hypothyroidism by serial screenings of thyroid function and blood sugars.

However, we leave the fourth pillar of wellness, memory and cognitive health to chance. We are fearful of being proactive. We succumb to clever marketing based on fear rather than facts. Part three of this series will outline a proactive plan for managing cognitive wellness.

The article I wrote two weeks ago, “Timeline for the Development of Alzheimer’s Disease,” got me thinking. I have known for some time that most progressive dementing conditions unfold over the time span of decades, but having concrete data makes the natural history of Alzheimer’s disease all the more clear.

Brain changes associated with Alzheimer’s disease are found 25 years before onset of symptoms. One way to use these data is to label the changes as being Alzheimer’s disease early on. Indeed, this is what has been done with the new diagnostic criteria. There are many unfortunate effects of doing this. We do not know the base rate of those who have these brain changes and don’t go on to show symptoms of Alzheimer’s disease. Recall that imaging studies produce a high rate of false alarms when completed on general populations rather than selected study groups (“Brain Scans Lead to Misdiagnosis of Alzheimer’s Disease” April 2012). Part of the problem is that, according to the time line, imaging studies don’t appear to detect changes until 15 years before symptoms.

Earlier diagnosing is not a good solution. Early labeling someone as having Alzheimer’s disease decades before symptoms appear will do more harm than good. There are a number of psychological implications of diagnosing too early: stigmatization, feelings of hopelessness and despair, and misdiagnosis. Early identification of brain changes that are associated with Alzheimer’s disease indicate that intervention studies need to be started when participants are in midlife – for late onset Alzheimer’s disease – and cover a time course of at least 15-20 years. This is a far cry from current intervention studies that may, at best, cover a five year span and only begin after symptoms have arisen. We need intervention studies that fit the model of longitudinal aging studies such as the nun studies. This would finally clarify the benefits of interventions such as cognitive stimulation, exercise, supplements, etc.

The dilemma as I see it is that medical interventions carried out by this model are risky. We would be permanently altering the physical characteristics of the brain without knowing what the long term and possible detrimental effects might be. Furthermore, we would be intervening on some who will never show symptoms. I am not sure how to resolve these issues.

On a practical level, the good news from the time line is that memory loss shows up ten years before symptoms of Alzheimer’s disease. It’s clear that not all memory loss is due to Alzheimer’s disease and that not all memory loss will go on to produce dementia. While we wait for better data on long term life style and medical interventions, we need to change our mindset. We regularly consent to blood tests and physicals to monitor our health. Yet we leave memory to chance. Why isn’t memory evaluation a part of everyone’s wellness program?

The screening tests available are for memory loss and Alzheimer’s disease (the most common being the Mini-Mental State Exam) are too superficial, are not diagnostic, and don’t show changes until 5 years before symptoms of Alzheimer’s disease occur. Next week, I will lay out a simple plan for being proactive based on what we know now.

Diabetes mellitus is associated with increased risk for developing Alzheimer’s disease. As with many areas of science, the data are inconsistent. Few studies have explored the impact of using diabetic medications and the development of Alzheimer’s disease. One study, Rotterdam study, showed that diabetics treated with insulin had a greater risk for developing Alzheimer’s disease. On the other hand, another study demonstrated that diabetics treated with insulin or oral antidiabetic drugs had a lower density of neuritic plaques (associated with Alzheimer’s disease) than individuals who do not have diabetes.

A recently published study (Journal of the American Geriatric Society, 2012, 60, 916-921) explored the association between diabetes and the use of Metformin (a popular antidiabetic drug). The data were gathered from the United Kingdom General Practice database that was established in 1987. The study was completed by assessing the data banks for individuals aged 65 and older who had a first-time diagnosis of Alzheimer’s disease between the years 1998 and 2008. The final analysis was completed on 7,086 individuals and an equal number of individuals who did not have a diagnosis of Alzheimer’s disease. The average age of cases was about 81.

On the whole, there was no increased risk of developing Alzheimer’s disease in individuals who were diabetic when compared to those who were not diabetic. Also, the risk of developing diabetes was not different for those controlling their diabetes with medications versus those who controlled their diabetes through life style.

The diabetics who used metformin to control their blood sugars had a greater risk of developing Alzheimer’s disease than those using other medications. On the other hand, those who controlled blood sugars by the use of sulfonylureas did not show increased risk of developing Alzheimer’s disease. The use thiazolidinediones (diuretics such as HCTZ) did not increase risk of developing Alzheimer’s disease.

Simply, treatment of diabetes with Metformin may increase the risk of developing Alzheimer’s disease whereas treatment with sulfonylureas, insulin (when necessary), or other diabetic drugs did not increase the risk of Alzheimer’s disease. Although not the final word, these data are encouraging as they did not show an overall association between diabetes and Alzheimer’s disease and they suggest one factor that needs to be considered when choosing the best medication for diabetes.

Unfortunately, these data do not indicate reduction of risk for Alzheimer’s disease in treated diabetics. Diabetes appears to pose a greater risk for contributing to vascular dementia (dementia due to stroke) than for developing Alzheimer’s disease. Both forms of dementia can be quit disabling and produce overlapping symptoms. Furthermore, many dementias have mixed etiology (multiple causes). Still the greatest risk factor for Alzheimer’s disease is age. Aggressive screening for management of diabetes needs to be in everyone’s life plan.

How long does it take to develop Alzheimer’s disease? A study published in the New England Journal of Medicine (July 11, 2012) indicates that a rare and aggressive form of Alzheimer’s disease produces measurable changes 25 years before clinical symptoms appear.

There is a rare form of familial Alzheimer’s disease where carriers of a gene mutation are afflicted with symptoms in their 30s and 40s (20s for some). This early onset (autosomal-dominant) form of Alzheimer’s disease is inherited in a pattern similar to Huntington’s chorea. We inherit pairs of genes (one of two possible from each parent). In early-onset Alzheimer’s disease one gene is normal and the other carries the program for the illness. In carrier families half of the children with develop the disease and half will not.

Fortunately, most cases of Alzheimer’s disease are late-onset – we are more likely to be afflicted by the disease as we age –especially into our 80s and beyond. It has been clear for some time that Alzheimer’s disease develops well before we can detect actual symptoms. Studying cases of early-onset disease allows us to follow those with the faulty gene and better understand the course and timeline for the disease. The hope is that the process is similar for those with late onset disease.

The Dominantly Inherited Alzheimer’s Network, DIAN, study of these high risk individuals completed numerous baseline and clinical/cognitive assessments on those enrolled in their data bank. The following timeline emerged:
1. Concentrations of amyloid and tau proteins were elevated 25 years before the onset of symptoms in carriers.
2. Siblings without the mutant gene had no detected change in these markers.
3. Imaging studies detected amyloid deposition in the brain (using the Pittsburg marker) 15 years before symptoms.
4. Increased concentrations of tau protein and brain atrophy were detected 15 years before symptoms.
5. Memory loss and cerebral hypometabolism were detected 10 years before symptoms.
6. Changes in the Mini-Mental State scores were found 5 years before expected symptom onset.
7. Criteria for dementia were detected on average 3 years after symptom onset.

Clearly, early-onset Alzheimer’s disease unfolds over the course of 2-3 decades. We assume the same or a longer time course would be evident in late-onset Alzheimer’s disease. Furthermore, current medical screening tests pick up the changes too late for proactive interventions as they don’t detect changes until 5 years before serious symptoms appear. In short, current intervention studies fall quit short. Longer intervention studies are carried out over the course of 3-5 years and most studies are of much shorter duration. They don’t inform us of significant outcome for a process that unfolds over decades.

The long build up is good news. We have time to set up interventions. For example, memory decline begins at least a decade before dementia. The focus of interventions must be memory. You must learn skills before you need them. It is the habits, routines, expertise that will serve us as well as family that care about us better. We don’t wait until we are 80 to assess and build our financial assets. The same principle holds for memory. The earlier we get assessed and start out memory plan, the better the quality of our life.

I had two discussions this last week about the distinction between delirium and dementia. The first was with a client who underwent major surgery several weeks ago. I have been following this client for several years and several evaluations demonstrating excellent memory. Subsequent to surgery, the client developed a delirium which has cleared. However, for the first time his evaluation scores have dropped. Second, the discussion during Minder’s Keepers at the Alzheimer’s Support Network turned to the same topic.

So let me try to clarify the difference between a delirium and a dementia. By the dictionary a delirium is “an acute mental disturbance characterized by confused thinking and disrupted attention usually accompanied by disordered speech and hallucinations.” By the same dictionary dementia is “usually progressive condition marked by deteriorated cognitive functioning with emotional apathy.”

The critical thing to know is that a delirium has a sudden onset and is reversible in time. A dementia often has a gradual onset and is irreversible. The table below may help with understanding the differences that mark a delirium and a dementia. Be aware that someone with a dementia can also develop a delirium (such as from hospitalization, illness, or medications). In other words this is not an either/or difference.

DELIRIUM DEMENTIA
ONSET sudden or acute often gradual
COURSE rapid changes stable
DURATION hours to weeks months to years
ATTENTION fluctuates normal
HALLUCINATIONS/DELUSIONS often sometimes
MOOD anxious/fearful apathy

Delirium is especially disturbing to caregivers and staff. Delirium is especially likely in those with cognitive impairment or dementia. Delirium adds temporary but substantial burden to all involved. Furthermore, delirium often accelerates decline in those with dementia such as Alzheimer’s disease, Parkinson’s disease, or Lewy Body disease. In a recent study (Annals of Internal Medicine, June 19, 2012) 25% of hospitalized patients with Alzheimer’s disease developed delirium while hospitalized and 79% of those patients were institutionalized, developed further cognitive decline, or died within the next three years.

There are multiple possible causes of delirium. These conditions may confound the diagnosis of dementia and add to the burden and complexity of caregiving.
1. Metabolic disorders such as thyroid disease or diabetes
2. Malnutrition such as vitamin B deficiency
3. Dehydration
4. Neurologic disorders such as stroke
5. Infections such as urinary tract infections
6. Trauma such as head injury, surgery
7. End of life
8. Drug/alcohol use or withdrawal

There are a number of events that may increase the risk of delirium. We need to be especially vigilant in those who are aged, demented, dehydrated, cognitively impaired, on multiple medications, have had a previous delirium, or are severely stressed (e.g., hospitalized). Despite the often profound and frightening symptoms of delirium, it is in itself a temporary condition. It will resolve with treatment of the underlying cause, compassion, and patience.

Depression in midlife and late life is associated with an increased risk for developing Alzheimer’s disease and/or vascular dementia. The most recent study was completed on 13,535 members of Kaiser Permanente (a not-for-profit health plan with its home in Oakland, CA) and published in the Archives of General Psychiatry (2012, 69, 493-498).

The design of the study was retrospective and included any member who had a medical diagnosis of depression or neurological based diagnosis of Alzheimer’s disease or vascular dementia. Records were reviewed from 1964 to 1973 (midlife) and 1994 to 2000 (late life). Depressive symptoms were reported in about 14% of those in midlife and about 9% of those with depressive symptoms in late life.

Those who were depressed at midlife had a 20% increased risk of dementia (either Alzheimer’s disease or vascular dementia). Those who were depressed in late life had a 70% greater risk and those with depression in both mid-and late life had an 80% increased risk. Overall 1,020 members were diagnosed with dementia (about 14%) with an average age of about 81 at follow up.

These results may reflect either that depression in mid and late life is causal in development of dementia or is an early symptom of dementia. This distinction is very important from a treatment perspective. If depression is causal, then treatment should focus on depression (psychotherapy and/or antidepressants). The assumption is that successful treatment would reduce the risk of developing dementia. This, of course, can only be resolved by conducting an adequate randomized clinical trial of treatments for depression. On the other hand, if depression is an early symptom of dementia, then treatment strategies should focus on cognitive/lifestyle therapy and proactive planning.

In any event, those who develop mid-or late life depression should be carefully evaluated and followed not only for mood but also for cognitive function by neuropsychological assessment. Screenings are too insensitive. A baseline measure of memory function should be determined and there should be comparative follow up assessments to allow appropriate treatment planning.

If you or someone you care about shows depression in middle or late life, ask for a complete evaluation of both memory as well as depression. The following signs suggest a need for such an assessment:

1. Easily lose patience
2. Easily to anger
3. Loss of energy
4. Loss of or too much sleep
5. Appetite changes
6. Sexual changes
7. Find no joy in any aspect of your life
8. Frequent crying spells
9. Feel a constant sense of depression, anguish, and despair
10. Don’t think you can go on much longer.
11. Wish for relief by death

Two recent headlines caught my attention. “Eating berries linked to delay in cognitive decline” (Annals of Neurology, 2012, April 25) and “Coffee may ward off progression to dementia” (Journal of Alzheimer’s Disease, 2012, 30, 559-572). I drink blueberry flavored coffee each morning. Does this give me double the protection?

The first study demonstrated that higher consumption of either blueberries or strawberries “slowed memory decline by up to 2.5 years. The study, Nurses’ Health study, had a very large sample size, 16,010, with an average age of 74. Cognitive function was assessed every two years between 1995 and 2001. “Protective” associations were found for women who ate 1 or more servings of blueberries per week or ate 2 or more servings of strawberries per week.

On the surface the findings look encouraging. But the rub comes with some of the details. Most importantly, the study controls for age and education – a good thing. However, the study did not take into account life style choices. When the results of the study were conducted balancing those who exercised more and had higher income, the findings were attenuated. The bottom line is that it may be general life style choices and more money to buy healthy foods that accounts for the effects of not eating berries. So go ahead and eat strawberries and blueberries. But don’t forget to also exercise and engage in a generally healthy lifestyle.

The second study focused on coffee consumption (measured plasma levels of caffeine) in participants who were diagnosed with Mild Cognitive Impairment (MCI). The findings suggest that drinking 3-5 cups (500 mg of caffeine) was associated with failure to progress from MCI to dementia ‘over the course ‘of 2-4 years. More specifically, those diagnosed with MCI demonstrated significantly lower plasma levels of caffeine compared to those with normal memory. The study also reports lower plasma levels of caffeine in those diagnosed with dementia than those with normal memory. But this finding was not statistically significant which means it should not have been reported. As in the case of eating berries, the effects may have been a result of uncontrolled for lifestyle or health reasons not caffeine.

Statistical side bar. I have often seen studies report findings as being “nearly statistically significant” or as “trends toward statistical significance” There is no such thing. Statistical analysis is a tool for decision making. Either a finding is significant or not based on a priori decision rules. It’s sort of like one cannot be nearly pregnant. We have enough confusion from conflicting studies. We don’t need to clutter our understanding of these important issues with “trends.”

The conclusion I draw from these two studies is that there are still no magic bullets. We need randomized clinical trials to sort out factors that slow or prevent progression of memory loss or neurological disease. I will continue to eat berries as I have been and drink my two to three cups of coffee per day. I am also hedging my bets by being on the treadmill and staying engaged with the world.

I am often asked about the use of medications to help with adjustment to memory care or skilled nursing facilities. For example, I was asked “would my mother do better in a memory care unit if she was given Xanax.” This is a logical and compassionate question. As with most persons who need the total services, her mother is mildly agitated and trying to plan how to escape now that she lives in a locked memory care unit. The intent of the question is to find out if use of a calming medication makes the adjustment easier.

The issue of adjustment is complex and involves both the memory impaired person and their caregiver (spouse or child). In my experience it often takes several weeks or months to actually get settled with a move and all of the associated changes. Who wouldn’t rather keep living in their home? Many in these facilities spend an adjustment period where they pack and unpack their clothing each day. Furthermore, the need for placement negates easy explanations. By the time placement is needed, the severity of the dementia negates those complex abilities of comprehension, reasoning, and accurate self perception. Indeed, if the person could accurately see their level of decline, they would ask to be moved into the facility.

Is use of the medication for staff convenience? Staff convenience is not a good reason to use medications. Staff in most facilities should be trained to handle many instances and types of agitation without the need to resort to drugs. Is the medication being used because either the resident of the facility or staff at risk of harm from the agitated resident for staff safety? If so, at least brief use of a medication can be quite helpful in many cases.

Is the medication being requested to assuage guilt over placement? I have never seen a person placed too early in a memory unit. Despite this, most caregivers will suffer from feelings of guilt, second thoughts on placement, and complex grief. Also, the caregiver is in difficult position after placement where the resident does well all day with activities. But visitation from family triggers the natural desire to be taken home, which of course breaks your heart. This is part of the adjustment for both of you and will usually take weeks to unfold.

Finally, there is no evidence that I am aware of that addresses the issue of whether medications speed up the adjustment to placement or makes it easier. If we compare the feelings after placement to grief, there are to date few studies suggesting that use of medications either makes grief easier or resolve more quickly. In some instances medications interfere with adjustment.

Whether to mediate to help adjustment to locked memory units has no universal answer. It depends on multiple complex factors. In most cases that I have encountered, it appears best to avoid a knee jerk use of medications like Xanax, antiseizure drugs, or neuroleptics. Rather, use stimulation, redirection, and reassurance first. Only use medications when nondrug therapy fails or there is danger. Finally, reassess after time to determine if the medication is still needed.