Life and Memory Center

Now that 70 is in my rear-view mirror, I am increasingly attracted to articles with tittles like “A Plan For Successful Aging” (health.harvard.edu). I am officially one of those “geriatric” clients with whom I have worked for nearly three decades. I am one of the “young old.” I feel that the quality of the rest of my life requires that I don’t focus on the past – I can’t change it. I am the result of my genetics and cumulative experiences (the easy and the difficult, the mistakes and the successes). What follows is my general outline to protect my future as well as I can.

1) Be proactive. Don’t wait for the first fall to take action. I have been “thinking about” getting a medical alert device for my mother-in-law. She recently fell in the bathroom and was unable to get up. Twelve hours later, someone from the facility where she lives missed her and decided to check. Fortunately, there were only a few bruises. She now has a medical alert bracelet and grab bars by the toilet. Knowing isn’t doing. We all need to make safety checks of our home and take action to make our homes safer. Consider a safety evaluation by either an occupational or physical therapist.
2) Reduce the risk of falls. Falls are increasingly a “big deal” as we age. Exercise to keep strong. Do yoga or tai chi for balance.
3) Where should I live? Despite our strong desire to live alone or with our companions in our home, we need to face the fact that there are risks that we need to consider. Isolation and lack of engagement can have devastating consequences for the quality of life as we age. I need to soul search and move to a community with multiple services and opportunities for engagement before I actually need it. This is especially true if you have considered a Continuing Care Retirement Community, as you may not qualify if you have medical or cognitive changes.
4) Get advanced directives in place. Do you have a living will? Do you have a Durable Power of Attorney or equivalent? Who will you manage you money, credit cards, and investments? How will you know when it is time to turn over the checkbook? Who will manage as your financial and medical advocate/surrogate? Do they know where things are and what they need to manage?
5) Attend to risky behaviors. Limit alcohol consumption. Drive within the limits of the changes in senses and speed of thinking/reacting that come with age. Have a plan for how to know when you are no longer safe to drive and how you will get around. Work with your physician to manage health variables that you can influence such as blood sugars and blood pressure.
6) Exercise most days of the week.
7) Stay intellectually and socially engaged.
8) Liberally use external memory supports like calendars and to do lists. Don’t forget the One Minute Rule.

Stay ahead of life where you can. It’s the quality of the years not the number that makes for successful aging. Even with the challenges presented by progressive diseases like Alzheimer’s, Parkinson’s, and diabetes, they take years to unfold and don’t always produce disability.

Benzodiazepines such as Klonopin (generic = clonazepam), Xanax (generic = alprazolam), Ativan (generic = lorazepam) have a long and controversial history of use to treat behavioral challenges in those with Alzheimer’s disease. These disturbances range from agitation, anxiety, delusions, and hallucinations to sleep disturbances. The controversy deepened with the recent finding of a correlation between benzodiazepine use and risk of dementia. This risk appears to develop with chronic (i.e., daily) use of these medications for three or more months.

At this time there is no agreement on use benzodiazepines as an alternative to antipsychotics, which have potentially serious side effects in the elderly. Current guidelines recommend use of benzodiazepines be limited to a few weeks despite the fact that they are often used for years. Long-term daily use of benzodiazepines is associated with increased risk of falls, dependence, and withdrawal (“discontinuation”) syndromes, which is also a problem with antipsychotic, antidepressant, and antiseizure medications.

“Use of benzodiazepines in Alzheimer’s disease: a systematic review if the literature” (International Journal of Neuropsychopharmacology, 2015, in press, PMID 25991652) provides a current update. The review was undertaken in an attempt to provide evidence-based suggestions for use of benzodiazepines in dementia. There were 657 articles between considered between 1983 and 2015. Unfortunately, after careful review there were only 18 articles that met research standards high enough to be included in the review. Among the findings were:
1) Benzodiazepine use in combination with any other psychotropic medication increased risk of falls with higher doses producing more falls.
2) Nearly 10% of Alzheimer’s patients in skilled nursing homes were treated continuously with benzodiazepines for 2 or more years. Use in skilled nursing homes may be as high as 50%.
3) Benzodiazepines are more frequently prescribed for patients with a diagnosis of Alzheimer’s than vascular dementia.
4) Benzodiazepines are often used in combination with other psychotropic medications increasing the risk of drug interactions.
5) Benzodiazepines were more often used in Alzheimer’s patients who had arthritis or rheumatism than patients without that diagnosis. This implies misdiagnosis when pain may be the source of difficult behaviors rather than dementia.
6) Long-term use of benzodiazepines – especially long-acting – is associated with increased speed of decline, increased severity of dementia, and shorter time to death.
7) Benzodiazepines further impair cognition.
8) There is little good evidence to make conclusions about the effects of benzodiazepines on sleep disorders in Alzheimer’s.
9) Targeted use of benzodiazepines is helpful in managing episodic agitation.

After review of all well designed studies the authors concluded that they could offer “no clear guidelines” for the use of benzodiazepines to manage behavioral disturbances associated with Alzheimer’s disease. Despite widespread use benzodiazepines are less than 50% effective to manage agitation. This finding may be do to the fact that much of the agitation is triggered by such things as pain, overstimulation, understimulation, or fatigue, which should be the focus of intervention. We clearly need to spend more research dollars on clarifying guidelines for use of psychotropic medications to treat behavioral disturbances in dementia.

Memory loss can result from a number of neurological conditions. Alzheimer’s disease is not the only cause of memory loss. There are at least three clinically important memory systems:
1) Episodic
2) Semantic
3) Working
4) Procedural

Episodic memory is the most common clinical memory complaint and most thoroughly researched and assessed (e.g., recall of lists of words). Episodic memory involves the recall and recognition of personal episodes and experiences. What did you eat for breakfast? What was the most recent movie that you saw? Where did you go for vacation? Episodes are the scripts of your life that involve the sense of time and self.

Episodic memory involves three steps:
1) Encoding. Awareness and attention are required for an event or episode to be recorded.
2) Consolidation. The brain process that actually lays down the memory “trace” for later recall or recognition.
3) Retrieval. Recall or recognition of events and experiences.

Episodic memory often involves the hippocampus and adjacent brain structures. The most famous example of what happens when the hippocampi are removed was Henry Molaison (HM). He lived between 1926 and 2008 and had neurosurgery to control seizures in his mid 20s. This caused him to lose his ability to consolidate new experiences into long-term memory – called anterograde memory.

This is the memory system that is most problematic in early Alzheimer’s disease. However, there are a number of additional neurological disorders that may also induce episodic memory loss: traumatic brain injury, stroke, brain infections (e.g., encephalitis, meningitis), toxic or nutritional conditions, Transient Global Amnesia (profound sudden onset that is time limited), some forms of epilepsy, Lewy body disease, Parkinson’s disease, and hippocampal sclerosis (often mistaken as Alzheimer’s disease).

Semantic memory involves forgetting of acquired knowledge. This shows as loss of facts or concepts, loss of words, loss of word meaning, loss of knowledge of the use or relationships of things. This usually presents as problems in language like trouble naming objects, word finding, or word substitutions. This memory system worked very well in HM. Semantic memory deficits are usually associated with damage to the frontotemporal areas of the brain. Often semantic memory deficits result from strokes or head trauma causing sudden onset. In other cases the onset may be slow and progressive in conditions like primary progressive aphasia or Alzheimer’s disease.

Working memory is the active maintenance of information in the mind. It involves attention and concentration. Working memory is the multitasking capacity of the brain. Why am I in this room? It contributes to encoding of episodic memory. Working memory is better considered an executive function rather than a memory system and was fine in HM.

Procedural memory is cognitive and behavior skills. These memories are often not verbalized but rather performed automatically – skills that persist over time after learning them. These skills include things like how to use a computer, how to use a TV remote, driving, playing a musical instrument, art, and swimming. HM not only did well with procedural memory but was able to learn new skills that he did not know he had learned. Procedural memory deficits are sometimes evident in Parkinson’s disease, Huntington’s disease, and cerebellar disease. They may show up later in the course of Alzheimer’s disease.

As you can see, memory disorders are complex and not always caused by Alzheimer’s disease even in the elderly. Memory changes and treatments require carful, thorough neuropsychological, neurological, and medical evaluation.

Howard Gardner proposed the theory of multiple intelligences in 1983 (howardgardner.com) to more broadly interpret intelligence than can be done by standard IQ tests, which often best measure the likelihood of doing well in school. But as we all know, intelligence is far more than doing well in school. The idea, as I understand it, is that the brain has multiple skills, ways of understanding and knowing the world. At the beginning of life, these skills allow us to develop and learn to competently master tasks and information.

According to Gardner, there are eight “intelligences.” These are:
1) Verbal-linguistic intelligence: ability to analyze written and verbal information.
2) Logical-mathematical intelligence: ability to use and understand calculations, symbolism, and mathematics.
3) Visual-spatial intelligence: ability to use and understand maps, design, visual arts, and architecture.
4) Musical intelligence: ability to produce and compose different patterns of sound.
5) Naturalistic intelligence: ability to use and understand botanical, zoological, meteorological, geological features of the world.
6) Bodily-kinesthetic intelligence: ability to develop complex athletic skills such as dance.
7) Interpersonal intelligence: ability to understand others’ desires, motives, and intentions.
8) Intrapersonal intelligence: ability to recognize and understand ones own desires, motives, and intentions.

These different intelligences may be operationalized as talents that we all have in varying degrees. They represent areas where our brain may more easily acquire skills or information. For example, poets need to be strong in verbal-linguistic intelligence whereas artists need strengths in visual-spatial intelligence and ballerinas need to be strong in bodily-kinesthetic intelligence. We may be “bright” in one skill set more so than another. However, probably the most effective learning and the most accomplished among us engage multiple intelligences. These are not simply learning styles, as is often mistakenly thought, but rather varying ways to engage with the world.

Engagement is the key to enhancing quality of life as one ages – especially if one is unlucky enough to be afflicted with a dementing condition. All too often we try to engage those with diminishing cognitive skills by relying mostly on verbal-linguistic intelligence. But I know more than I can say. Even in decline there are islands of retained competences but they may not always be activated by verbal instruction. People seem so surprised when someone who is demented still plays the piano or generates complex drawings. But these retained talents make sense from the perspective of multiple intelligences.

We need to broaden the idea of brain stimulation and engagement beyond that of computer games – no offense to Lumosity, Bingo, and games of trivia. We need to creatively take advantage of what the brain can still do. We need to form group activities around skill sets rather than tasks. This involves engaging in art, music, walking in the woods, playing physical games/sports within the limits of retained competence. This involves more effort and creativity from caregivers and facilities.

The cholinesterase inhibitors like Aricept (i.e., donepezil) have been available for treatment of dementias such as Alzheimer’s disease for two decades. It is clear that long-term use of these medications slows the progression of Alzheimer’s disease (in those who tolerate them) and that discontinuing these medications after extended use produces a risk of more rapid decline even in those who are in middle and late stage dementia.

The standard of care for use of medications to treat Alzheimer’s related dementias recommends use of a cholinesterase inhibitor (donepezil, Exelon, and galantamine) starting in Mild Cognitive Impairment and early stage dementia. Namenda (i.e., memantine) has been available to treat middle and late stage (but not early stage) dementia for over a decade. A recent study (Cumulative, additive benefits of memantine and donepezil combination over component monotherapies in moderate to severe dementia: a pooled under the curve analysis (how’s that for a title?), Alzheimer’s Research and Therapy, 2015, 7, 28 PMID 25991927) indicates that adding memantine to donepezil improves outcome over either medication used alone.

The study combined results from 4 randomized clinical trials (RTCs) conducted over 6 months for a total study population of 1408 participants in middle to late stage Alzheimer’s disease (MMSE scores of 3-14 of a possible 30). There were 4 treatment conditions: placebo, memantine only, donepezil only, or combination of memantine and donepezil. Scores on standardized cognitive, functional, and behavioral scales were used to assess outcome.

The results indicated that:
 All participants who were treated with placebo declined on all outcome measures compared to either combined treatment or monotherapies (i.e., donepezil or memantine alone).
 Donepezil treatment alone was more effective than treatment with memantine alone.
 The combination of donepezil and memantine together was clearly the most effective treatment and “clinically significant.”
 The actions of the two medications were additive but not synergetic as has sometimes been stated by some.

These results make it clear that currently available medications for middle and late stage Alzheimer’s like dementias remain effective even into late stage disease. Furthermore, adding memantine to donepezil (and presumably other cholinesterase inhibitors) improves outcome over either treatment alone.

It is increasingly clear that becoming demented as we age is more than just Alzheimer’s disease. There may be few if any “pure” cases of Alzheimer’s disease. It may be the added wear and tear from added medical burdens in conjunction with the pathology of Alzheimer’s that leads to dementia. We already test for factors such as B12 deficiency, thyroid deficiency, and acute infections as they may impact cognitive function and are treatable conditions.

However, we ignore many diseases that may take a toll on brain function and cognition. We are just coming to terms that such events as surgery, treatment of cancer, sleep apnea, and repeated head injuries have short and long term effects on cognition. The cumulative load is too much for biological and psychological compensation with time and aging. One often-ignored disease is lung disease such as COPD (chronic obstructive pulmonary disease) and asthma. Most with these diseases do not become demented but these conditions add to the risk and are often modifiable/treatable (Lung disease as a determinant of cognitive decline and dementia, James Dodd, 2015, Alzheimer’s Research and Therapy, 7, 32 PMID 25798202).

Lung disease increases cognitive impairment and brain pathology. We can add this to a list that includes smoking, cardiovascular disease, depression, physical inactivity, hypertension, diabetes, drugs, sleep disturbance, infections, and social isolation that puts us at risk for cognitive decline and are modifiable by life style and medical management starting at least in middle age. There is an independent association between lung function and cognitive performance.

The two main obstructive lung diseases are COPD and asthma. COPD is the most common lung disease. It is preventable and treatable. If left unchecked it is progressive and involves an inflammatory response to noxious particles or gasses most often secondary to tobacco smoke. Asthma is more frequent in children and young adults and is associated with inflammation and atrophy of lung tissue in response to allergy and hay fever rather than smoking. Treatment with inhaled bronchodilators and steroids improve both lung and cognitive function. Both conditions are often associated with cognitive impairment.

Although the focus of belief has been that hypoxia is the culprit, there is cognitive dysfunction in COPD without hypoxia. More likely the problem stems from cerebral small vessels disease, microbleeds in the brain, chronic inflammation, and oxidative stress. Smoking leads to decreased volume and density of frontal grey matter, risk of stroke, and cerebroatrophy. Finally, COPD has been linked to reduced hippocampal volume – a critical memory structure. In one study half of those with serious acute exacerbations of COPD had moderate to severe cognitive deficits that did not resolve after three months.

We can conclude that lung disease – especially COPD is a modifiable risk factor for cognitive decline and may contribute to the development of dementia. Lung disease independently from Alzheimer’s pathology is linked to memory/cognitive impairment but may or may not be associated with the rate of decline. Finally, the mechanisms for causing brain pathology are very complex.

Lumosity, the “brain training company”, is booming. Everyone is looking for the magic, quick, easy way to fortify his or her brain in hopes of staving off dementia. However, know this. The brain is designed to elaborate itself from experience (in a very broad sense). The foundation of our being is learning and memory. That got us through growing up and it will get us through aging if we just do what comes naturally and you don’t have to pay a fee. That is, interact with the world about you.

There is so much marketing and appeal to science – that is often not founded in reality – that one can lose track of a very simple fact. The brain enriches itself by the mere act of engaging in the world. Here are some ideas from an article in the Business Insider (http://www.businessinsider.com/daily-habits-to-be-smarter-2015-5). The list is not and cannot be exhaustive but gives a range of possibilities. Doing these things may not actually make you smarter but they will enrich the connections in your brain.

1. Have an idea. I think its actually hard not to have an idea each day. It may not be the idea that changes the world but few ideas do.
2. Read a newspaper. Be sure not to skip ideas that challenge your beliefs.
3. Play devil’s advocate. Reading an editorial may help with this.
4. Read a book.
5. Watch an educational video or take a free online course.
6. Check with your favorite sources of knowledge. Yes, sports center counts.
7. Share what you have learned with others. We know and remember best that which we can and do explain to others.
8. Make a to do list including learning new things.
9. Track what you have accomplished from the to do list.
10. Create a “stop doing” list. For example, I get caught up in playing hearts and spider solitaire. I need to do it less often. Maybe I need to set a timer so I can get more interesting things done.
11. Keep a journal of what you have learned that you want to remember.
12. Talk to someone you find to be interesting.
13. Be with people who are smarter than you.
14. When you hear something interesting, follow up on it.
15. Learn new words to help you express yourself.
16. Get outside of your comfort zone. If you are really willing to confront a common fear, join toastmasters.
17. Travel and explore new places and cultures.
18. Set aside time to do nothing.
19. Engage in a hobby.
20. Exercise.

I am sure you can add to this list. The point is to paraphrase Carl Rogers, don’t just grow older bur rather continue to grow as you grow older.

Has the diagnosis of Alzheimer’s disease outlived its usefulness? I have felt for some time that the diagnosis of Alzheimer’s disease has no clinical utility. First, one can have Alzheimer’s disease and never become forgetful. Second, one can have Alzheimer’s disease with memory loss but not become demented. Third, one can become demented and not have Alzheimer’s disease. Fourth, we do not know the cause of Alzheimer’s disease as evidenced by the massive failure of amyloid treatments to date. Fifth, there is no pure case of Alzheimer’s disease in the elderly. Finally, there is no specific treatment unique to Alzheimer’s disease.

The real life problem is not that someone has Alzheimer’s disease but rather the practical issue is whether one can be competent to handle the tasks of independent living: self-care, toileting, dressing, doing the checkbook, getting around, learn, being in relationships, etc. Some are more proficient at any of these tasks than others. But the clinical problem develops when one becomes disabled, unable to carry out independent activities in the real world. Dementia is a form of disability. Dementia is by definition irreversible. Dementia may come on suddenly from such things as head injuries or strokes. Dementia may develop over time from such things as Alzheimer’s disease, Lewy Body disease, or Huntington’s chorea.

Based on autopsy findings very few elderly that become demented have pure Alzheimer’s disease. For example, as we age, the brain is affected by strokes. Most of the strokes are “silent” that is without symptoms. There are small strokes that can be seen upon imaging techniques such as the MRI but we are not aware of events marking them. There are strokes so small that they cannot be seen via imaging like the MRI but can be seen under the microscope during autopsy. These silent strokes alone may double the rate of dementia. It may not be the pathology of Alzheimer’s disease alone that causes one to become demented but rather the added burden of a second pathology that overwhelms the ability to compensate.

So rather than use a term like Alzheimer’s disease wouldn’t we be better off just using labels like Mild Cognitive Impairment (still independent) and dementia (no longer independent)? If we made this change it would allow us to focus our attention on practical skills like doing a checkbook, driving, being able to express oneself, preparing meals, etc. This removes all of the connotations that a label like Alzheimer’s disease has. Rather we could then assess functional skills and develop treatments plans to address them.

We could also become more proactive. For example, we can address issues like cardiovascular disease to reduce (not prevent) the likelihood of ever becoming demented, even if we are unlucky enough to have the pathology that is Alzheimer’s disease. Aggressively treating such factors as blood pressure may reduce the odds of becoming demented by 50%. We can further protect ourselves by not smoking, limiting consumption of alcohol, managing diabetes, exercising, and eating a heart healthy diet.

It is time to redirect our thinking. The label “Alzheimer’s disease” limits our thinking and has outlived its usefulness. It reduces our options. It creates a hopelessness that may be unnecessary. Alzheimer’s disease is a label not an explanation for certain ways the brain becomes less competent with advancing age in some but not all.

Despite the “therapeutic nihilism” that seems to dominate thinking about Alzheimer’s disease there are essential components that should be included in managing Alzheimer’s. Jeffrey Cummings details these components in the Annals of Clinical and Translational Neurology (A practical algorithm for managing Alzheimer’s disease: What, when, and why? 2015, 2, 307-323, PMID 25815358). An effective treatment plan should include:

Strategies for managing risk factors starting at least in middle age. Consider adopting a “Mediterranean style” diet; minimize consumption of alcohol; supplement with omega 3, B vitamins, and E (if already clinically diagnosed); exercise regularly; engage in intellectual interests; become educated about Alzheimer’s disease; participate at some level in music and art; get adequate sleep; manage stress, let a pet adopt you; include stimulating day programs appropriate for the various stages of memory loss for those already diagnosed; and use a calendar and external supports to stay engaged in life.

Once diagnosed, consider treatment with appropriate medications: cholinesterase inhibitors (Aricept/donepezil, Exelon, or galantamine). These medications slow/delay decline in many if tolerated. All three have similar efficacy and follow up is needed to assess and manage possible side effects. Begin assessing and monitoring cognition and ADLs 6 months after initiation of treatment. Consider adding Namenda in moderate to severe disease.

There may be potential for including a trial on therapeutic foods such as Axona, NAC, and Vayacog under clinical supervision. This seems more experimental to me at this point based on the data available.

Manage “comorbidities.” These include cardiovascular disease, thyroid function, sleep apnea (doubles the risk for Mild Cognitive Impairment and dementia over the course of 5 years), osteoporosis, cancer, glaucoma, depression, hypertension, diabetes, infections, incontinence, and rheumatoid conditions. These diseases increase the rate of cognitive decline and frailty.

Assess safety. Have an OT and PT assessment in the home. Remove firearms. Monitor and assess the appropriateness for driving.

Have legal directives in place. Make sure you have a durable power of attorney and living will in the context of your life planning. Develop a plan for assessing, protecting, and transfer of financial and medical decision making as the disease progresses.

Know the options for in-home and residential care should they be desired or needed. Discuss these issues early and openly. Have a plan that you hope to never need to use to protect against decision making during crisis.

Don’t forget to include family and caregivers in planning and treating Alzheimer’s disease. They are the foundation for success and practical management in everyday living. They need support, education, guidance to help the not only to be effective caregivers but also to be sure they do what is necessary to have a life beyond caregiving.

There are two main pathways for cognition as we age: normal aging and cognitive decline (abnormal aging). It is important to understand that aging is not a disease, Alzheimer’s is. It seems clear that there are things we can do to protect and enhance cognition during normal aging. What is not clear is whether there are things that we can do to protect against abnormal aging.

Staying sharp cognitively is a goal for many seniors as evidenced by the popularity of “brain fitness” programs such as Lumosity. Lumosity alone has some 70 million members from 180 different counties. It’s marketing ads boast that it is “scientifically” developed. There is no clear evidence that mastering their 40 games makes any real world improvement in everyday cognitive functioning let alone protects against abnormal aging.

A recent report from the Institute of Medicine makes several cogent points. Clearly there is great variability in cognitive abilities in the aged. Many stay very sharp as they age. Two cognitive changes are associated with advancing age. First, as we age we process information more slowly than we did when we were younger. Second, as we age we multitask more poorly. Most of us actually do a good job of compensating for these changes in such skills as driving. For example, we slow down, leave more following distance, and limit night driving in unfamiliar places.

Even subtle changes in cognitive skills increase vulnerability for some. We may become more susceptible to scams so we become more suspicious. We may become less able to make complex financial decisions so we involve family and advisors. We may have difficulty in an increasingly complex technological society so we solicit guidance from our children and grandchildren. Long-term memory stays intact as evidenced by knowledge, skills, and routines despite decline in working memory. Hence we use more external memory supports.

The report makes several recommendations based on accepted evidence for helping maintain cognitive skills as we age. These suggestions include:

1. Stay physically active.
2. Control high blood pressure and diabetes. So goes the heart, so goes the brain.
3. Don’t smoke. Limit consumption of alcohol.
4. Some medications can be especially problematic for cognition as we age. These include antihistamines, sleep aids, anti-anxiety medications, older antidepressants, bladder medications, pain medications, and anti-seizure medications.
5. Stay socially and intellectually active.
6. Get enough sleep. Indeed, “power” naps can help memory and improve alertness.
7. Be wary of products that promise to improve cognition. This includes supplements as well as brain fitness games. The “MIND” diet has not been adequately tested.

Of course, these are the recommendations that we read about often and we have known for a long time. We can better manage cognitive changes that arise from normal aging. The suggestions for preventing abnormal aging remain elusive at his time.