Life and Memory Center

To quote from my article for August 2011,  “It is clear that anesthetic agents may be neurotoxic for some and more so after 60.”  This statement was predicated on findings from that time suggesting that undergoing general anesthesia may cause cognitive decline especially in the elderly.  Delirium and postoperative cognitive decline are the two most common untoward effects of surgery.  Delirium is transient and obvious but may last days to weeks.  Postoperative cognitive decline is a more long lasting condition, often subtle at first.

But not so fast, understanding is a process that evolves over time and must integrate new information as it becomes available.  A new study (Mayo Clinic Proceedings, May 2013) states that there is no association between anesthesia and dementia.  The data were obtained from medical records on nearly 2000 cases.  Results were based on individuals that were older than 45 when first undergoing their first anesthesia.

There was no association of anesthesia with dementia in this study.  Furthermore, there was no association between the number of procedures and the development of dementia.  The results were similar for those diagnosed with Alzheimer’s disease as for those with dementias from other causes.  There was also no association between either duration or type anesthetic agent used and development of dementia.

The authors of the study feel that it may not actually be the anesthesia that causes postoperative dementia but rather that postoperative dementias are a result of a preexisting but yet unrecognized cognitive decline.  Also supporting this idea is that there are enduring effects of hospital acquired delirium in patients that already are diagnosed with Alzheimer’s disease.  The rate of decline is about two times faster in those with Alzheimer’s who develop an in-hospital delirium when compared with those who do not.   Delirium is a transient condition that clears and returns affected persons to their baseline level of cognition.  Five years after hospitalization those with Alzheimer’s who developed delirium declined more quickly.  The delirium may be transient but the risk for more rapid decline is not.

The bottom line is that the association between anesthesia and risk for developing a dementia remains unresolved.  The anesthesia may not be the culprit.  What seems to be clear is that those with pre-existing cognitive decline, whether recognized or not, are at greater risk of bad outcomes (delirium or postoperative decline) than those who have intact cognitive functions. The decision of whether or not to have surgery under anesthesia remains complex as we age and needs to weight potential gains and costs.  The clearest advice is to avoid purely elective surgical procedures especially in the elderly and  if they are cognitively compromised.

I just finished reading a very interesting book that was suggested by a couple of my clients.  They are aware that I love cats.  I recall the empty feeling that Pamela and I had between cats.  Pepper, our cat of 22 years, died and we spent a year and a half without another cat.  Our home lacked completion during that time.  We are so pleased to have Gracie and Vanna add their energies to our home.

Making Rounds with Oscar is set in a nursing home. David Dosa, the author of the book, and a special cat named Oscar are the two main characters in this memoir.  David Dorsa is the attending physician at a nursing home in the northeast.   Being classically trained, he begins by being skeptical about the ability of a resident cat, Oscar, to sense and to seek out residents of the facility who are in their last few hours of life.

The story evolves as David comes to understand the reliability of Oscar to not only sense death but to be present for the dying resident and family members.  Oscar’s presence provides all with a sense of comfort and compassion at a difficult time.  There are many rich descriptions of families coping with dementia and end of life issues as well as facing the need to let go of someone they love deeply.  It is a lesson in how to be with rather than how to do for someone – the essence of palliative care.

Dr. Dosa avoids maudlinism and instead shares many of his personal and professional struggles with life and death.  The case histories are reminiscences that not only allow Dr. Dosa to grow but also display familys’ ability, in part thanks to Oscar, to heal after the death of a loved one.  Furthermore, Dr. Dosa reveals that he is suffering from a progressive chronic disease that allows him to deal with his patients as more than another case study or research project.  We get to see someone who is more than an observer looking in.  He has to look out from within his own deteriorating condition.

The book is short and engaging.  I advocate being proactive rather than reactive about aging and progressive diseases of aging.  It is never fun to confront disability, death, and nursing homes.  Making Rounds with Oscar provides all of us a way to think through and discuss the difficult issues of dementia, skilled care, and death in an approachable compassionate way.  I recommend Making Rounds with Oscar to anyone who has ever or ever will be touched by disabling/dementing illness or death.

I am often asked about potential treatments for Alzheimer’s disease.  The intention behind the question is to solicit my assessment of whether there are any medications that show promise for the future.  Anyone who has talked to me or followed my columns knows that I am frustrated by the rigid commitment and inflexibility of many clinical trials that focus on treating brain proteins called amyloids that cause the build up of plaques in the brain.  This strategy has channeled so many intellectual and financial resources into a collective tunnel vision despite many failures of the concept.

There are two recent studies that merit attention in that they each add intriguing findings that are not directly connected to amyloid pathology.  They focus on slowing progressive diseases as well as suggest new strategies in the search for disease modifying treatments of Alzheimer’s and related diseases.

Diabetes is a slowly progressive disease that has been linked to Alzheimer’s disease.  Indeed, the reasoning is that brain insulin resistance and deficiency is associated with Alzheimer’s disease as well as with Type II diabetics.  Rates of Mild Cognitive Impairment and diabetes are higher among Type II diabetics than non-diabetics and intranasal administration of insulin may preserve cognitive functioning in those with Mild Cognitive Impairment.

A small study (The Journal of Clinical Intervention, May 20, 2013) reports that Byetta, a glucagon related diabetes medication, used as a supplement to Parkinson’s drugs improved function in Parkinson’s patient after a year.  Control patients on Parkinson’s drugs only showed decline.  Hence, there is emerging theory that at least some forms of progressive neurological disease may be a “brain form of diabetes.”

An interesting article was published last year suggesting that 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. 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.

An article published in Neurology (May, 2013) reports that patients with a history of squamous or basal cell skin cancer had a reduced risk of developing Alzheimer’s disease over several years of follow up and had better performance on cognitive testing when entering the study.  Melanoma may not offer the same protection.

We need to put more research money and intellectual assets into pursuing findings such as these.  I am hopeful that we can find ways to slow the progression Alzheimer’s and related brain disorders.  But we need to overcome the inertia of pet theories that have not produced clinically useful results.

I just returned from a speaking engagement in Tampa where I discussed “Treating progressive memory loss.”  The thing to note in the title is that the focus is on treating memory –there’s something you can do – rather than treating a disease – there’s confusion about what to do.  The treatment for Alzheimer’s disease needs to be proactive rather than reactive.  The focus of treatment is to plan for a good life (everyone’s long-term goal regardless of memory) as you age even if your memory declines.

 There are two requirements of a good treatment plan.  First, build memory supports before you need them – use the One Minute Rule.  Second, build a life of engagement.  The popular advice is to learn something new or buy a brain fitness program.  Indeed, I recently read a neurologist’s suggested treatment plan for a client with the amnestic (struggles to learn anything new) form of Mild Cognitive Impairment.  The recommendation was that he learn a new language to stimulate his brain.

The problem here is that the client was being set up for failure. Learning a new language is difficult enough for most of us and impossible for someone with diminished short-term memory.  Relearning or expanding on skills or knowledge that one already has as well as by learning something new can stimulate the brain.   We fail to assure people that participation in any engaging activity stimulates the brain.  Stimulation does not have to put such a load on short-term memory.   There is a better approach for those with declining short-term memory.

I once had a forgetful client who tried to learn Spanish, a new language for her, to keep her brain sharp, only to be frustrated and feel “stupid.”  After a discussion of her memory and talents, she dropped Spanish lessons in favor of French lessons – a language that was rusty but already in her brain.  She thrived in French and felt good about herself again.

I recently had a discussion with a client who asked if he should buy a computer program to stimulate his brain.  As it turned out, he has mild short-term memory loss and is not good with computers – a new skill he needs to acquire when new learning is the challenge.  We discussed the trade-offs for him based on how his memory is working in the context of his life skills and interests.  As it turned out he learned to play the guitar as a youth but has not had time to return to playing until recently – a long-term memory already in his brain but is rusty.

We seem to make simple things so hard sometimes.  No matter how good or bad our memory, life is best spent in activities that we enjoy.

There is a strong belief among both the general population and medical practitioners that physical inactivity and poor diet are associated with cognitive decline as we age.  Physical conditioning and diet are closely associated with cardiovascular health that, in turn, is associated with heart disease and stroke.  Indeed, better physical condition as we age reduces some of the wear and tear of aging on the brain as evidenced by less atrophy and white matter disease with aging.

 Another recent study adds to the evidence that what’s good for the heart is good for the brain.  The study (“Cardiovascular health through young adulthood and cognitive function in midlife, Annals of Neurology, 2013, 73: 170-179) followed cardiovascular health of participants over the course of 25 years starting age 18-30.  The assumption was that those who maintained greater levels of cardiovascular heath would display better cognition in midlife.

Cardiovascular heath was determined by measuring seven factors that are influenced by life style choices we all make throughout our life.  The factors include maintaining healthy weight, eating a healthy diet, not smoking, maintaining physical fitness, keeping cholesterol below 200, controlling blood pressure, and keeping blood sugar below 100.  The hypothesis was that the greater the number of these factors kept close to optimal after 25 years the better the cognitive test scores (memory, speed of thinking, and executive function).

Indeed, the greater the number of cardiovascular health factors that remained optimal the better the scores for speed of thinking, memory, and executive function.  However, as might be expected scores on all of these variables were generally lower in middle age than when 25 years younger.  The factors most predictive of maintaining better memory into middle age were not smoking, keeping total cholesterol low, and maintaining healthy blood pressure.  Interestingly, diet had little effect in this study.

Life style choices modestly impact our long-term health.  However, cardiovascular health is determined by both our choices and our biology – many will have suboptimal scores on many of these variables even when they make good choices as they age.  We need better data for the impact of treatments of these long-range health outcomes, as this study did not separate those who naturally benefitted from healthy choices versus those who were optimal because of treatments (e.g., taking blood pressure medications, statins) as well as choice.  In short, we need to control what we can such as exercising regularly and not smoking.

The lesson is that we need to be strategic and proactive throughout our life toward the goal of having better cognitive functions as we age.  Efforts at maintaining cardiovascular health as we age pay dividends in the long run.  What’s good for the heart is good for the brain.

I keep hoping for more useful research on treatments and management techniques that may potentially benefit those with memory loss and their caregivers.  There are three recent studies that caught my attention as examples of movement in the right direction.

First, “The effect of stimulation therapy and donepezil on cognitive function in Alzheimer’s disease” (BMC Neurology, 2012, 12, 59).  The study compared the effects of stimulation therapy, treatment with donepezil (Aricept), or to combined treatment during the first year after diagnosis with mild to moderate Alzheimer’s disease.  Stimulation therapy consisted of multiple elements including physical activity (e.g., dancing, walking, fitness training), as well as cognitive and social activities (e.g., reading, listening to music, crossword puzzles, reminiscence) for at least 30 minutes each day 5 times per week.  Donepezil (or placebo) was started at 5 mg and increased after four weeks to 10 mg for the duration of the study.

Interestingly, all treatments faired the same after one year.  On average, all participants had similar cognitive scores at the beginning and the end of the year.  Although there are many limitations and interpretations of these findings, I was surprised that the combination of drug therapy and stimulation therapy did not improve outcome at one year.  We need more of this type of studies with better client selection and over a much longer duration.

Second, there is widespread and prolonged use of antipsychotic medications in persons with dementia to manage such behaviors as agitation, aggression, delusions, hallucination, and/or mood changes despite warnings and cautions.  Even more troubling to me is that once these medications are started, they are continued indefinitely.  According to a recent literature review in the Cochrane Database Systematic Review (“Most dementia patients can safely stop antipsychotics,” Medscape, April 02, 2013) discontinuation of these medications does not cause relapse in most patients in skilled nursing.  This review should help remind us that all medications should be reviewed often and that antipsychotics in the demented should be written from the beginning with a taper/stop date.

Third, common clinical lore suggests that use of antipsychotics to treat behavioral disturbances in dementia may increase mortality.  A large prospective study in Japan compared those who were treated with antipsychotics with those who were not.  There was no greater mortality after 10 weeks for those on antipsychotics.   The most common causes of death were pneumonia, cardiovascular events, and cancer, respectively.

We need to extend and broaden our working knowledge through studies like these that challenge our assumptions and address practical issues regarding treatment and management of progressive memory disorders.  There are many questions; there is too much emphasis on finding the elusive cure and too little use of scientific methodologies to gather data that guide our day-to-day treatment decisions.

I read yet another newspaper article on Alzheimer’s disease touting “early diagnosis.” Now that it is clear that brain changes of Alzheimer’s disease develop decades before there are symptoms, the push is to make a medical diagnosis well before there are any symptoms. Furthermore, if we pursue this strategy, many (based on current data as many as 30%) will be diagnosed who will never develop symptoms. We will instill fear and hopelessness needlessly.

“Alzheimer’s disease’ a label that has no usefulness in the real world. Everyone with Alzheimer’s disease does not become demented. The label provides a false level of understanding along with an expectation that there is nothing that can be done. There are effective treatments for memory loss but they are not medical and therefore undervalued. Furthermore, a diagnosis should direct you to actions that tell you what to do. What do you do if you are diagnosed with Alzheimer’s disease?

The question is wrong. Ask instead what is the primary functional change that marks most progressive mental decline? The answer is that there are progressive changes in short-term memory – the ability to learn new information. The better approach is to target measuring short-term memory. If I am told that I have Alzheimer’s disease, there is no direct action to take. On the other hand, if I am told that I have changes in short-term memory, it is clear what to do.

If I have short-term memory loss, I can develop strategies that engage long-term memory. Memory loss occurs well before dementia. Do this while you are still in control of your future. It allows you to be proactive. You can get ahead of progressive memory loss. You can be proactive rather than reactive about your future. This proactive plan should be a part of advanced directives.

Simply, the plan needs to include family, as they need a say in the details. In addition to legal directives, the plan should address how to monitor ability to do complex and simple finances and cooking as well as how to transfer decision-making powers before they are compromised. The plan should advise on how to monitor driving, how to initiate cessation of driving, and how to have a life if I can no longer drive.

The plan should also direct others on how to make my life good even if I can’t remember what I just did or what to do next. If I am reduced to living in the moment, I need to make those moments joyful either by doing or reminiscing about the things I love. As I always tell my audiences, don’t make me play bingo. I’ll get ornery. Instead, I love to travel. Visit museums. Watch movies. Walk in the mountains. Play with my cats. Build my life around my retained interests and skills for as long as possible. I should put this plan in writing now in case I need it in 10 years. The objective is to have a good life even if my memory fails.

The second most feared medical diagnosis – next to cancer – is Alzheimer’s disease, the most common cause of dementia.   What is Alzheimer’s disease?  This not such an easy question to answer as it may seem.  Ultimately, the diagnosis requires confirmation by autopsy or biopsy but even here the diagnoses is uncertain.  A diagnosis is made by clinical criteria based on typical features.

“Typical Alzheimer’s disease” mainly affects the elderly – onset over 65.   Most often Alzheimer’s disease is “sporadic” – meaning there is no prior family history.  The symptoms do not develop rapidly but rather come on slowly over the course of many years.  The first sign of possible Alzheimer’s disease is short-term memory slips such as forgetting conversations, getting lost, or forgetting events.  As the condition progresses there are deficits in skills in addition to memory such as problems with naming objects, problems with arithmetic, problems with multi-tasking, and/or problems with reasoning.  Despite withdrawal and apathy, social skills are retained in the early stages.  Progression unfolds over the course of several years.

There is a tendency to diagnose Alzheimer’s disease in everyone over 60 that displays memory loss or confusion by default.  However, there are treatable conditions that may be missed without adequate diagnostic workup.  For example there are the “worried well.”  These are persons with mild memory complaints that are difficult to differentiate from normal aging.  There is evidence that a portion of the worried well actually have very mild Alzheimer’s disease that will become clearer over the next few years.  Typical memory screenings are insensitive to these changes at a time when proactive treatment is essential.  The best place to start if you are worried is with a rigorous evaluation by a memory expert – often a neuropsychologist.

What are some common mimics of Alzheimer’s disease?  Depression is associated with and sometimes confused for Alzheimer’s disease.  However, the depression must be severe to create actual confusion, which is more tied to attention/concentration than actual short-term memory loss.  Late life depression is a risk factor for Alzheimer’s disease and, while very treatable, needs to be followed over time by memory assessments and proactive planning.

Metabolic disorders (e.g., low B12, low, diabetes, or high thyroid levels) and infections (e.g., herpes encephalitis, tertiary syphilis) may be associated with confusion and are treatable. Tumors and normal pressure hydrocephalus (shunting may make Alzheimer’s disease worse so careful differentiation is essential) are rare but need consideration.  These are very avoidable mistakes with proper medical evaluation.

Cognitive impairment due to vascular disease may closely resemble or may accompany Alzheimer’s disease.  Vascular cognitive impairment, like Alzheimer’s disease, is much more common with age.   Despite traditional dogma, vascular dementia may slowly progress rather than manifest as a “stepwise” decline.  Treatable issues like hypertension, smoking, alcohol, and diabetes need to be addressed during the evaluation.

Other mimics include frontotemporal degeneration, Lewy body disease, and posterior cortical atrophy.  Frontotemporal disorders first show up as changes in personality or expressive language deficits rather than memory loss.  Lewy body disease often has less severe memory loss, Parkinson’s features, and hallucinations.  Posterior cortical atrophy presents with problems of sequencing, spelling, and arithmetic rather than memory.

A more detailed review of these and other considerations can be found in Practical Neurology (2012, 12, 358-366).  Don’t just assume that mental changes associated with aging are by default Alzheimer’s disease and hopeless. If you have concerns, don’t put off a good memory assessment.

It has become increasingly clear that most progressive dementias slowly unfold over the course of several decades.  For example, Alzheimer’s disease forms decades before there are any signs or symptoms.  It doesn’t appear suddenly or show up as a “conversion” from Mild Cognitive Impairment.   This is good news.  We can be proactive by life style and planning years ahead instead of just reacting to changes after they occur.  Life style interventions must start decades before problems show themselves.

 The issue to resolve is what life style changes is worth the effort.  Exercise is the one factor that is emerging as a clearly protective of the brain.  Many short-term studies have suggested that increasing levels of fitness now pays benefits for future brain health.  The Cooper Center Longitudinal Study, Cooper Clinic in Dallas, published a study that prospectively followed a large number of participants over the course of several decades (nearly 25 years on the average).  Additionally fitness was measured objectively, with a treadmill test, not by self-report.

The study included 19,458 men and women who were in midlife (average age = 49.8) beginning in 1971.  Fitness level was measured by maximum time on treadmill test.  Dementia was determined from Medicare records for participants who were 65 and older by December 2009 – 1659 cases of dementia in this study.  Fitness at midlife was associated with a lower risk of dementia from all causes (e.g., Alzheimer’s,  vascular).

There are a number of possible benefits of fitness for the brain.  First, high levels of fitness are associated with reduced effects of the wear and tear of aging (i.e., less shrinkage and lessened white matter disease in the brain).  Second, maintaining higher levels of fitness reduces the risk of diabetes and hypertension.  Third, exercise may improve hippocampal (the short-term memory structure) function and induce the release of brain growth factors, which increase neuroplasticity.

Even if you are over 50, it’s not too late.   The best way to protect your brain is through physical exercise.  It is estimated that fewer than 10% of the US population reach the minimal goal of at least 2.5 hours of moderate exercise per week.   You only need a good pair of comfortable exercise shoes and comfortable clothing.   Start slow and gradual and work toward consistency.

Alterations in short-term memory are the hallmark of Alzheimer’s disease as well as a whole host of other brain changes that can, in time, erode our ability to make complex decisions such as handling finances or making legal documents.  The changes are subtle in onset and slow in progression.  Neither our own self-evaluation nor that of competent professionals can detect the changes by observation in the very early stages.  Despite our personal beliefs about our selves, most will not “know” when to give up the finances or when to stop driving.

 Changes in memory are not the province of medicine.  Medical screenings are insensitive to early changes in memory and brain scans produce too many false positive results.  Verbal learning tests used to assess short-term memory are better at detecting risk than are biomarkers such as PET scans. We need to refocus our efforts away from diagnosis.  A diagnosis of Alzheimer’s disease is demoralizing.  Monitoring memory is empowering.  There is so much you can do about changes in memory.  We need to detect changes and to monitor memory as comfortably and routinely as we manage our wellness.

I propose a simple plan.  There is no brief screening that will serve us well to protect our future.  These screenings are devised to detect Alzheimer’s disease, which is more than just memory loss.  Screenings are too insensitive and superficial.

I have given this quite a lot of thought as a result of my discussions with Tony Curatolo, Ciccarelli Advisory Services.  This is a plan that will be helpful to allow informed decisions regarding your ability to make complex decisions regarding medical, financial, or legal matters:

1. We all need baseline memory evaluation that is friendly, thorough, and affordable.
2. The assessment should consist of an interview that is structured around memory, verbal problem solving, and speed of thinking.
3. The assessment should directly involve family members (involved in all aspects of the assessment) and include detailed feedback on how your brain is working (strengths as well as weaknesses).
4. I suggest the following components of the basic evaluation for someone without noticeable concerns: a quantifiable checklist (also completed by someone who knows you well) on the present state of your brain, a verbal learning test, a paper and pencil arithmetic test, a measure of speed of thinking, a measure of verbal problem solving, and a global index of confusion.
5. This evaluation is very much like routine blood work or monitoring your investments.  It provides quantifiable scores and feedback that you can follow over time to monitor progress and to anticipate future needs.

I have developed such an evaluation that I plan to make available in the near future.   Be proactive with your memory just as you are with your health, finances, and legal directives.  The best strategy for beating Alzheimer’s disease is to proactively manage and monitor your memory.