Monday, May 29, 2017

The Coming Pandemic of Lyme Dementia

There are many known causes of dementia. One of these causes are bacteria. Bacteria are usually ignored despite its historical and current significance in dementia research.  A hundred years ago it was well known that syphilis—a bacterium—was the only known cause of dementia. The bacteria interferes with the nerves until it reaches the brain where it destroys the brain from the inside. In the end, the expression of long-term syphilis is dementia—Neurosyphilis. Alois Alzheimer wrote his post-doctoral thesis (Habilitationsschrift) entitled “Histological studies on the differential diagnosis of progressive paralysis.” on neurosyphilis before his supervisor Emil Kraepelin propelled him into the history books by defining Alzheimer’s disease as a new disease in 1911. [1]
Neurosyphilis was very common in the 1900s. Between one in four to one in ten people in mental institutions were there because of neurosyphilis. Eventually syphilis kills its victims. Before the introduction of penicillin in 1943, syphilis was a common killer. In 1929, among men, the death rate from syphilis was 28.3 per 100,000 for Whites and 97.9 per 100,000 for Blacks [2]. The similarities between syphilis and dementia were addressed repeatedly in the early literature in Alzheimer’s disease [1]. Because syphilis can now be treated easily and cheaply, it has nearly been eradicated. But there is a new bacterium threat emerging—one that can also cause dementia.
Today, the main bacterial threat to acquiring dementia comes from Lyme disease—a bacterium borrelia burgdorferi. Lyme disease is transmitted to humans through the bite of infected blacklegged tick. These ticks are themselves infected by feeding off diseased insects and birds, which bring the infection from across the globe. Worldwide there are 23 different species of these Lyme disease-carrying ticks.
Lyme disease is the most common disease transmitted by animals in the northern hemisphere and it is becoming an increasingly public health concern [3]. Not only because Lyme disease is a debilitating disease, but because eventually Lyme disease has been shown to cause dementia—Lyme dementia [4]. Science has not identified the mechanism for the development of Lyme dementia. The American psychiatrist  Robert Bransfield has been documenting some of its neurological expressions, but so far there is a lack of emphasis in the research community on exploring these clinical features. 
Ernie Murakami, a retired physician, has been monitoring the spread of Lyme disease across the world. With more than 65 countries that have the blacklegged ticks which transmit Lyme disease, this is a worldwide pandemic.The prevalence of Lyme disease reporting varies dramatically. Canada reporting the lowest cases in the world, with 1 case per million, while Slovenia reports 13 cases per 10,000. In the United Sates the Centers for Disease Control and Prevention reports that more than 329,000 people are likely to be infected every year in the U.S. alone. Only one in ten cases are reported since clinicians are not looking for Lyme disease. This estimated number of annual infections is higher than hepatitis C, HIV, colon cancer, and breast cancer. Lyme disease accounts for more than 90% of all reported cases of diseases transmitted by animals (vector-borne illness).
With any good public health strategy there needs to be a two pronged response. One is to address the clinical effects of the disease and the other is to address the underlying cause. In the United States, although research funds to examine and explore cures for Lyme disease are minimal, this avenue is likely to see the most significant increase. But this would be folly without addressing the underlying cause of the disease. Addressing these underlying causes will however be challenging.
Harvard Medical School Center reports that areas suitable for tick habitation will quadruple by the 2080s. But there are more pressing changes that will happen in our lifetime. Deforestation and climate-induced habitat change are affecting insect which carry diseases like malaria and Lyme disease. Slow climate change, urban growth in areas next to forests, reforestation following the abandonment of agriculture, and increases in the deer, mice and squirrel populations (among many others) which harbor these ticks.
Malaria and Lyme disease are both projected to increase. Even taking a more conservative estimate (all of the USA, most of Canada, all of Europe, Middle East and China), more than half the world’s populations are exposed to Lyme disease. A proportion of these populations will become infected with Lyme disease and eventually some will develop dementia. Pure Lyme dementia exists and reacts well to antibiotics [4].  Is public health ready to address this?
© USA Copyrighted 2017 Mario D. Garrett 


[1] Garrett MD (2015) Politics of Anguish: How Alzheimer's disease became the malady of the 21st century. Createspace. USA.
[2] Hazen H.H. (1937). A leading cause of death among Negroes: Syphilis. Journal of Negro Education, 310-321.
[3] Pearson S. (2014). Recognising and understanding Lyme disease. Nursing Standard, 29(1): 37-43.

[4] Blanc F., Philippi N., Cretin B., Kleitz C., Berly L., Jung B., ... & de Seze J. (2014). Lyme Neuroborreliosis and Dementia. Journal of Alzheimer's Disease, 41(4): 1087-93.

Monday, May 1, 2017

Learning about Aging through Film: The Narrative Arc

The use of film to explore concepts in gerontology. This is one of a series of five lectures on the role of film in gerontology. Spoiler alerts, if you have not seen these films, this analysis necessitates exposing the plot. These notes are intended for you to click on the movie trailer sequentially with the analyses.

The narrative arc in film is a static story board of how a story evolves and develops, both evident as well as imagined. How older people are portrayed in film is best described through the interpretation of this narrative arc. An arc is the linear development of a story—a beginning, a middle and an end.  An alternate method of analyses would be through the more limited interpretation of context, character, symbolism, and other constructs.

One of the first films describing a simple story about older people is the 1952 Japanese film Ikiru by the acclaimed director Akira Kurosawa—acclaimed for the Seven Samurai, Rashomon, and Ran. Ikiru has a fairly simple narrative arc. A bureaucrat, on the cusp of retirement, is informed that he has terminal cancer. The narrative arc focusses on the main character in the film attempting to find meaning and leaving behind a legacy in his life before he dies.

This simple story highlights that after one’s entire life spent doing what you are supposed to do—work, maybe family—that at the end what is important is relationships. At the end, he finds some solace among his younger mates, where he finds friendship.

This narrative arc, an old man at the end of life, was further developed by another seminal director, Ingmar Bergman who in 1957 wrote and directed Wild Strawberries.

Filmed in black and white, perhaps in homage to Ikiru, the film goes further in search of the meaning of one’s life and leaving a legacy. Following a fairly similar story of an accomplished bureaucrat—this time a professor—Wild Strawberries explores the question of what was it all about? The lost meaning is a reflection that the character’s internal story did not go far enough to include getting old. We do not have ambitions for getting old, and once we get there, we remain without a plan. Wild Strawberries has been described as Bergman’s attempt to justify himself to his own parents. The narrative arc told through actual and dream experiences, mixes ghosts, fantasies and reality. Admired but not loved, the protagonist starts to explore what the continuation of his story in older age should be. Like Ikiru, relationships seem to be the answer.
Such a conclusion is not far-fetched from what we observe at the end of life.

In 2012 Bronnie Ware, an Australian palliative care nurse, wrote The Top Five Regrets of the Dying: A Life Transformed by the Dearly Departing. Our two male protagonists in Ikiru and Wild Strawberries follow these regrets. These misgivings focused on having unfulfilled dreams and unrequited loves. Not having the courage to follow their dreams, where (mostly) men tended to regret working so hard. Stifling feelings in order to settle for a mediocre existence. And not staying in touch with their friends, and loved ones. And the final regret is not allowing oneself to be happy. They got stuck in a rut. The agreement between the narrative of these two films and the five regrets of dying people is stunning.

The films’ narrative arc, from a negative view of aging, exposing a slow hemorrhaging of life force, the story transforms to positive highlights of friendship and family. That it is not too late to address these regrets.  But what if this transformation did not take place? If the dystopian view of aging remains without the salvation of a new-found narrative what would be the result? This is the story of the two protagonists in the 2015 Italian film Youth.

Paolo Sorrentino’s film centers on two close friends sharing a vacation at an exclusive Swiss spa. The two protagonists are, a director who continues producing the same kind of films, surrounded by increasingly younger writers. While the other protagonist is a music composer who has decided to retire. What we have to work out is that the composer stopped composing—to the chagrin of many—because of his wife’s dementia which he hid from everyone including his daughter. He has made changes to address this trauma and his aging. Negative events in life change our narrative arc. In contrast, the other character, the director, only had one story—to remain doing what he did in the past. He did not have a different story for when he got old, and the quality of his work diminished. At the end, his suicide was the only answer to his failing career since he did not have a plan B, an evolving narrative arc. We have a starkly different outcome for what is portrayed as equally successful early careers.

This theme of different projections of the story line is best seen in the whimsical 2013 documentary, directed by Zachary Heinzerling, on Cutie and Boxer. Two married aging Japanese visual artists, living in New York city, where one reached their azimuth of success a few decades ago, while the unknown and subservient wife is launching her trajectory of ascendence in her narrative arc.

Cinematographically, a narrative arc can also be reversed. This is the beauty of film, we can explore the importance of a narrative arc by manipulating the sequence. This is a popular method in film, to imaging that a life’s story can go backwards or stay static, anchored to a particular age where you do not have to have a narration for an older age.

The digital masterpiece of the 2008 The Curious Case of Benjamin Button directed by David Fincher—of the fame, Fight Club, Se7ev, and Gone Girl—is based on the premise that while the main character is born old and starts becoming younger, everyone else gets older and dies. The only connection the main character develops in the film, is when his (descending) timeline converges with another character’s (ascending) timeline. This is the meaning of the story, that a meaningful relationship is shared with people in similar (time) context.

This theme is again is explored in the later 2015 film the Age of Adaline by Lee Toland Krieger where the main character is involved in a car accident resulting in a traumatic physical shock that enigmatically stops her aging.

The story focusses on two aspects of how meaningful relationship is shared with people in similar (time) context, when she experiences the aging and ultimate death of her daughter and the aging of her lovers.

What if you can go back and change your narrative arc. What would you choose? In Francis Ford Coppola’s 2007 Youth without Youth an older man is struck by lightning and starts to regress into his past. Not only was he getting younger, as the cases with The Curious Case of Benjamin Button, in his mind time was flowing back as well. This is the proverbial what would you do if you had to do it all over again.

Another technique used in film is to explore the “What If?” question. Made in 2009 Mr. Nobody was written and directed by Jaco Van Dormael. In this science fiction world where the last mortal is about to die at age 118, the protagonist explores three options that he could have made differently. Would the narrative arc result in a better outcome at the end of life?

In the end, the protagonist acknowledges that although every choice he has made had far reaching results in the future, ultimately none of the choices are good or bad. The interpretation is that as long as we make allowance for getting old everything will turn out well. Each will option will result in slightly different outcomes but all will have a coherent story. The narrative arc is written as we live life, and sometimes we are just too “busy” to envisage that anything will change. Despite us knowing, intellectually at least, that everything changes all the time.

A limited narrative arc, one that is missing a component for later life, relegates older age to a dystopian existence. Only by having an internal narrative that includes future dreams can there truly be a fully lived life. What better than a story of Burt Munro, a New Zealand amateur motorcyclist who wanted to break the world speed record and in so doing ignored age completely. This is the adaption of his story: The World’s Fastest Indian.

It took 20 years for the New Zealand director Roger Donaldson to make this film. In it, the protagonist narrative arc is changed when he tells of the death of his brother Ernie by a fallen tree—and, in Burt Munro’s real life, his stillborn twin sister—which changes the real life Burt Munro’s story and view of life. Negative events in life change our narrative arc. The beauty about this film is that the narrative arc ignored age completely. Suffering from angina and later a stroke in 1977, the real Munro at the age of 68 while riding a 47-year-old machine continued to set world speed records for 1,000 cc bikes. He did not use his experiences to dictate his age and his narrative arc did not stop at older age. He had his own ongoing story. In the film although there are characters that try and stop him from pursuing his narrative, the protagonist simply ignored them. Some of us are not so lucky.

Where we collude in this restriction is that we promote a restricted narrative arc for older people. Do a little exercise for me.

Let’s imagine that you have a 100-year-old woman that you are going to interview. What is the single question that you will ask her.

Write it down.

Then assume that you have a 16year-young girl coming to be interviewed. What single question would you ask?

Write that down.

The prediction is that you probably ask the older woman about her past and the younger woman about her future. You have already hemmed them into you view of what their narrative arc should be. With this knowledge in hand, let’s review a recent interview with Jerry Lewis.

An awkward exchange where Jerry Lewis’s narrative arc focusses on the future while the reporter is trying to force him—unsuccessfully, to the great strength of Jerry Lewis—to focus on his past.

To age successfully we must not only have a story that goes beyond adulthood—to extend into older adulthood—but we must also be vigilant against those who unintentionally try and demolish our narrative for living in older age, by translating it to “old” age. Our narrative arc is important because it is how we conduct our life, including into older age.

© USA Copyrighted 2017 Mario D. Garrett 

Saturday, April 1, 2017

Big Pharma Against Dementia

The World Alzheimer Report of 2011 reported that we do not know the benefits of screening and early diagnosis of dementia. We all assume that people should be checked early for dementia, but we do not know whether there is an advantage to be diagnosed with the disease. There are definitely negative repercussions—losing your driving license, right to conduct professional duties, enter into financial agreements, and sometimes even the right to conduct your own affairs. It seems that once you get diagnosed with dementia then you are left to fend on your own with your loved ones if you have any.

There is a disconnect between diagnoses—the identification of the disease—and prognosis—forecasting the progression of the disease and suggested treatment, therapy or support services. In the field of dementia, as with other diseases especially cancer, there lies an expectation that an early detection brings better outcomes: You live longer with less pain. But the reality is very different. New emerging research shows that our ambition to help dementia patients because of an early diagnosis is failing miserably.

In a French study in 2015, Clément Pimouguet and his colleagues reported that people with dementia who had consulted a specialist at the start of their disease, died earlier than those who only saw their general practitioner (GP) or did nothing. Sadly they found that there was no difference between participants who visited their GP and those who went without any clinical care.  Although those that went to see a specialist had much faster functional decline, their thinking ability was not much different from the other group. Why would seeing a specialist increase your likelihood of dying?

The lack of follow-up by the specialist was one of the reasons given for the higher rate of death. In 2017 Paula Rochon  and Jeremy Matlow and colleagues in Toronto, Ontario, reported that half of 2,998 nursing home residents with dementia were still getting questionable medication in their last year of life.  These medications might have had some benefit at the early stages of the disease but definitely have negative affect on the wellbeing of these confused patients. That a third of the residents did not see a specialist in the last year of life suggests that the medication was prescribed earlier on in the diagnosis and had not been reviewed since. Regular medication reviews will help to curtail unnecessary prescriptions.

It is likely therefore that too much and inappropriate medication is a culprit. In France only the specialist can prescribe drugs and this study found that half were prescribed antidementia drugs (46.2%); while the rest 12% prescribed antipsychotic drugs, 28% anxiolytic drugs, and 9% took psychostimulant. It is only when the diagnosis of dementia was vascular dementia and where some fo these drugs are not to be prescribed that seeing a specialist was found to be beneficial. Amelie Bruandet with the university of Lille, France and her colleagues found that with vascular dementia the shorter the delay between first symptoms and first visit, the longer patients survived. It could be due to medication, specialist do not prescribe medications that are killing dementia patients earlier.

It seems that we do not have any medication for dementia that is both effective and safe. In fact, all evidence points to dementia medication as being ineffective and in most cases dangerous. A conclusion that was arrived at by a 2014 study by two Dartmouth professors Steven Woloshin and Lisa Schwartz reporting for Consumer Reports. In addition to their costs—ranging on average $177-$400 a month—there was not one drug that they could recommend. Not one drug.

The logical assessment would be that since physicians have no medication to provide patients with dementia then following the Hippocratic Oath and “first, do no harm,” no medication should be prescribed.  But a 2015 study of elderly patients showed that anticholinergic medications given to patients with dementia—including antimuscarinics, tricyclic antidepressants, and first-generation antihistamines—are associated with an increased risk for dementia. Drugs being prescribed have an established evidence to increase dementia. Sometimes this dangerous medication is given for non-life-threatening disease such as overactive bladder. Christian Meyer from the University Medical Center Hamburg–Eppendorf in Germany, and his colleagues reported that more than one-quarter of older Americans with overactive bladder are given a prescription for oxybutynin, and one-third are given a refill, despite the established link between this drug and cognitive dysfunction in the elderly. In a 2015 survey of Medicare patients with dementia more than one in four were being prescribed "potentially inappropriate" anticholinergics.

The overuse of prescription of medication among older patients is ageist. We need to address this final bastion of stereotyping. We know that younger people with a similar disease are more likely to get therapy. But there is another negative consequence of this lack of knowledge. Physicians become shy at making prognoses. Although diagnosis is relatively easily, they can easily say it is Alzheimer’s disease or Vascular dementia without any liability issue, and most do despite evidence that they are likely to be wrong.  The patient is seriously sick, we can all see that. But once physicians start to define a timeline or sequence of how the disease will enfold, then they become exposed not only to the patient, but more importantly to the patient’s family, their medical institutional and legal liability.

In a short paper, Sonali Wilborn, and Navdeep Grewal, with Seasons Hospice and Palliative Care, Madison Heights, Michigan USA found that predicting mortality using current prognostic guidelines, fails in approximately a third of Alzheimer’s patients. Nicholas Christakis, a hospice physician takes it much further. He rightly laments the neglect of prognosis in medicine. Making a prognosis is messy and inaccurate. In 2000, he reports a study where only one in five timelines were accurate in forecasting death, more than half were over-optimistic while one in six were over-pessimistic. Being over-optimistic ensures that patients delay too long in sorting out their affairs.

The symbol of medicine is the rod of Asclepius—which has a snake coiled around a cane. It is carried by the Greek god Asclepius, a deity associated with healing and medicine. It is often confused with the caduceus which has a very different meaning.

The caduceus—depicting two snakes wrapped around a winged rod—is carried by Mercury the mythical messenger of the gods. Mercury is the guide of the dead and protector of merchants, shepherds, gamblers, liars, and thieves. In dementia care we might be confusing both the symbol and the objectives becoming the protectors of big pharma: merchants, gamblers, liars, and thieves. The abuse of older patients with dementia remains an unwritten chapter in the low point of medicine.

© USA Copyrighted 2017 Mario D. Garrett 

Bruandet, A., Richard, F., Bombois, S., Maurage, C. A., Deramecourt, V., Lebert, F., ... & Pasquier, F. (2009). Alzheimer disease with cerebrovascular disease and vascular dementia: clinical features and course compared with Alzheimer disease. Journal of Neurology, Neurosurgery & Psychiatry, 80(2), 133-139.

Pimouguet, C., Delva, F., Le Goff, M., Stern, Y., Pasquier, F., Berr, C., ... & Helmer, C. (2015). Survival and early recourse to care for dementia: A population based study. Alzheimer's & Dementia, 11(4), 385-393.

Rait, G., Walters, K., Bottomley, C., Petersen, I., Iliffe, S., & Nazareth, I. (2010). Survival of people with clinical diagnosis of dementia in primary care: cohort study. Bmj, 341, c3584.

© USA Copyrighted 2017 Mario D. Garrett  

Wednesday, March 8, 2017

Reminiscing Therapy and Dementia

In 1959, Erik Erikson published the first theory of personality that included older people. Before this, theories stopped at adulthood. His mentor, and father of psychodynamic therapy, Sigmund Freud, discounted older people since he believed they are not able to learn after the age of 50. Older age was defined as simply a decline from the apex of adulthood. This changed with Erikson’s final stage of personality development: Wisdom, Ego integrity vs. Despair. This stage related to those over the age of 65. The theory proposed that this is a time of acceptance of past life. By looking back and reconciling one’s accomplishments and losses, wisdom can be attained. If this process remains unfinished however then despair will ensue. Within this first theory of aging, “looking back” is integral to attaining wisdom and deflecting despair in older age.

At the same time, a new theory of older age emerged and can be traced to an earlier article published by Elaine Cumming, Lois Dean, David Newell, and Isabel McCaffrey in 1960. A year later Elaine Cumming and William Henry consolidated their thinking in a book, Growing Old: The Process of Disengagement which created such a backlash within the gerontology community. The idea behind this theory was to validate why older adults disengage from society. Criticisms of this theory were quick and harsh. But disengagement argument is much more subtle, and includes a discussion how society disengages older adults as worthless.

When older people face discrimination that insults their self-esteem, this creates conflict between one's past and the present self-concept.  One way to deal with this conflict—like any reaction to a trauma—is to move away. Older people move away from society in order not to get hurt. Around this time in 1964, in a book chapter, Robert (Bob) Butler argued that the vividness of the past is motivated by emotional needs in old age. These emotional needs he later labeled “ageism.”   Continuing with the Cumming and Henry argument that society mistreats older adults and that reminiscing allows older adults to maintain their sense of self.

Then in 1971 Charles Lewis in Reminiscing and Self-Concept in Old Age reported an experiment to test whether remembering the past allows older people to re-affirm their importance in the world. There were already studies showing that older men who reminisce tended to be less depressed and tended to have better survival (short-term studies.) But Lewis wanted to find out if reminiscing improved older men’s self-esteem especially after experiencing a threat. Lewis’s study showed that those that reminisce deflect some of today’s stressors by inflating one’s sense of self on the basis of past accomplishments or states. All of these set the stage for the pivotal experiment that was done in 1979.

Just under 40 years ago, a classic experiment became known as the counterclockwise study.  Then Harvard University social psychologist Ellen Langer and her colleagues conducted a strange experiment with a group of men between the ages of 75 and 80. For five days, the men were randomly assigned to one of two groups. Both groups were asked to imagine themselves at 55 years of age. One group was placed in an environment which mirrored the 1950s, with a redifusion (hard-wired radio), black and white tv with 1950s old radio and tv programs to match. Newspapers, magazine, decorations, furniture, food all matched the time period. While the second group was instructed to behave like they were 55 years old, but without the added environmental changes.
After only five days, the results were unexpected and dramatic. Men in both groups objectively looked younger by about three years, had improved hearing and memory, gained weight, increased muscle mass and had improved hand strength. These surprisingly quick results were more distinct for the group that lived “in time of their 50s” rather than the group that just reflected as their life was 20 years ago, although both groups improved.

Counterclockwise study catapulted the popularity of Reminiscing Therapy (RT). RT involves many variations. Traditionally—because it was the least expensive—RT involved the older adult discussing past activities, events and experiences. This was helped by the use of photographs, household and other familiar items from the past, music and archive sound and video recordings. Over the last decade, RT has become one of the most popular psychosocial interventions in dementia care. A quick review comes-up with more than 1,000 research papers published in 2016 on this topic. With a century of failures in finding any medication to help people with dementia, at least there was some hope that some therapy exists.

In 2005 Welsh scientist Bob Woods and his colleagues performed a review of four clinical trials—with controlled groups—and RT was found to improve thinking (cognition), mood and general behavior.  In addition, and as an added bonus, those caring for the patient also showed reduced level of stress and strain. Best of all, there were no known harmful effects. Outcomes that were again supported by more recent review in 2012 by Maria Cotelli and her colleagues. Although there are some reviews that show weak outcomes, the mounting evidence suggest that RT is—to varying degrees—effective in improving mood, thinking and well-being in patients with dementia. In a clinical area littered with failures, RT looked like a prime candidate for a miracle intervention. But how does it work?

Living with Alzheimer’s disease means to live in the moment, because the anchoring to the present and being able to predict a future has been disrupted.  Which explains why the placebo effect doesn’t appear to work with Alzheimer’s patients since they are unable to anticipate the future.  But could they relate to the past better, especially a time in the past when they were at their peak?  Anecdotally we know this to be the case.

Time constitutes an important factor in how we think of ourselves. The mind contains specialized areas for storing and retrieving knowledge about our personality traits across time. For example how we behaved as children.   People with dementia may be operating from knowledge of a former self, which may not match their current status. Neurological studies show how damage to certain brain structures result in very specific problems with time. So we know that time is an important function for the brain to process. Stanley Klein with the University of California Santa Barbara has studied this effect, summarizing these studies by identifying at least five functionally—and they argue—neurologically distinct components of how the brain stores time.

The brain is “concerned” with time. There is agreement among philosophers and neurologist that perception of time is an important human component. By thinking ourselves younger we allow our body and mind to behave as though we are younger and therefore we exercise these capacities more. Eventually such exercise improves our capacity. Becca Levy with Yale University and her colleagues has shown that positive age stereotypes, presented subliminally across multiple sessions in the community, lead to improved physical function that lasted for 3 weeks.  The same is true when competitive sportspersons are told that they are testing a new drug (placebo.) Not only do they perform better but their biomarkers all improve as well. This is not just a delusion, but an improvement. It seems that we have some control, or plasticity over our physical and mental functioning. And by pushing this plasticity—either up or down—we can modify our trajectory. This works with healthy sportspeople, people with dementia (because they can relate to the past) and also influence people’s longevity.

The idea that how we think of ourselves, regardless of our actual health, determines longevity seems outlandish. But numerous studies show just that. In a 23-year longitudinal study, Becca Levy reported that those individuals who had a more positive self-perception of aging lived an average of 7.5 years longer than did individuals with less positive self-perception of aging, even after adjusting for gender, socioeconomic status, loneliness, and functional health. In fact, perceived health was a better predictor of mortality than objective measured health (i.e., smoking and being overweight). Older adults who reported their health as poor, regardless of their actual health status, were six times more likely to die earlier than those who reported their health as excellent. We have some plasticity, some control over our physical health as well as mental health. We can “will” this plasticity.

The surprising outcome therefore, is that through Reminiscing Therapy, older adults with dementia are given a way to aspire to a time when they were better and this pushes them to try harder and as a result improve. Such plasticity is a degree change in a trajectory, not a cure.  Right now, there are some interesting developments in Reminiscing Therapy with dementia patients. The surprising take-home lesson for us is that it might also work for people without the disease, to push that plasticity as far as it will go to slow down that trajectory of aging.

Butler, R. (1964). The life review: An interpretation of reminiscence in the aged. In R. Kastenbaum (Ed.), New thoughts on old age. New York: Springer Co.

Erikson, E. H., Paul, I. H., Heider, F., & Gardner, R. W. (1959). Psychological issues (Vol. 1). International Universities Press.

Cumming, E., & Henry, W. (1961). Growing old. New York: Basic Books.

Langer, E. J. (2009). Counterclockwise. Random House Digital, Inc..

Some examples of Reminiscing Villages

© USA Copyrighted 2017 Mario D. Garrett  

Wednesday, February 15, 2017

Alzheimer's disease Repeating Failures

Chameleon Dementias
In 1976, a two-page editorial in the journal Archives of Neurology (now JAMA Neurology), penned by the neurologist Richard Katzman, transformed Alzheimer’s disease into an overnight sensation. The title of the paper emphasized the aim “The Prevalence and Malignancy of Alzheimer Disease: A Major Killer.” With the stroke of a pen, Alzheimer’s disease become the 4/5th killer in the world.

Katzman’s secret was simple. By eliminating the distinction between Alzheimer’s disease and senile (of old age) dementia Alzheimer’s disease become a major disease. Since “age” was the only reason that Alzheimer’s disease was defined as separate from senile (of old age) dementia—by Alois Alzheimer’s supervisor, Emil Kraepelin in 1912—this must have been difficult. But eliminating Alois Alzheimer’s definition proved surprisingly easy because there was no distinction in the first place. Katzman’s article by acknowledging this false distinction generated a lot of political capital in supporting the mission of the newly ordained National Institute on Aging. But if the reason for defining Alzheimer’s disease was wrong, what else is wrong with our interpretation of the disease?

And a hundred years later we still have no idea what causes dementia. Katzman threw us back into the past, and now, building upon this political tactic, researchers have again revisited the same issues that occupied them more than a hundred years ago.

From ancient Egyptians to the time of Alois Alzheimer in 1900s, dementia was known and rightfully, feared. Early Egyptians first document cases of what could be dementia more than two thousand BC. In a literary text from the beginning of the 2nd millennium BCE, a poem that damning description of aging is placed in the mouth of the embalmed city administrator and first historian Ptahhotep:

Senescence has come, elderliness descended.
Weakness has arrived, helplessness returns.
As one spends every night becoming more childish.
Eyesight has diminished, the ears become deaf.
Strength is perishing from my heart’s fatigue.
The mouth has fallen silent and cannot speak.
The heart is exhausted and fails to remember yesterday.
Bones ache because of length (of years).
Good has become evil.
All taste is gone.
What old age does to people,
Is evil in every respect
The nose is blocked and cannot breathe
from weakness in standing and sitting.

Throughout history, the diagnosis of dementia was confused with many other disorders. The cause was explained through the interpretative prism at the time. From the ancient Egyptians who conceived of dementia as a disease of the heart, to the middle ages where evil spirits invaded the body. Social norms and scientific fads at the time dictated how disease is explained, and dementia was no different. What was important in changing this was how we categorized diseases, especially dementia. And this formed in earnest in the late 1700s when French physicians took a more formal and objective approach to describing dementia.

Early French Scientists
We pick up the story in 1797 with the French psychiatrist, Philippe Pinel (1745-1826), who coined the term démence—deriving from the Latin de meaning "out of" and mens meaning "the mind." One of Pinel’s patients was a woman who over a period of just a few years, lost her memory, speech, and her ability to walk or use common household objects. After Pinel autopsied her brain. he described the woman’s brain as full of fluid and having dramatically shrunk to a third of normal size. In retrospect, Pinel’s patient is likely to have had normal pressure hydrocephalus (NPH). To this day NPH results in more than 9-14% of those admitted to nursing homes to be erroneously diagnosed with dementia. But despite this error, what was significant for the time was the identification of dementia as a biological disease.

After Pinel made this biological connection then it was up to another Frenchman, Jean Etienne Dominique Esquirol (1772-1840), to state more precisely the different types of dementias. Esquirol clearly distinguished dementia from mania—psychoses—and from mental deficiency. He also distinguished between acute, chronic and senile (of old age) dementia. His explanation is important as well since the different causes related to their distinguishing feature rather than their expression (i.e. they might be expressed in the same way). Acute dementia was short-lived, reversible, and followed a fever, haemorrhage or metastasis; chronic dementia was irreversible and caused by masturbation, melancholia, mania, hypochondria, epilepsy, paralysis and apoplexy; lastly, senile dementia resulted from old age, and consisted in a loss of the faculties of the understanding. Separating the observations of dementia into distinct categories based on what was assumed to be the cause, allowed for a more specific understanding of dementia. Although for senile dementia “age” was a good enough reason.

Pinel and Esquirol’s view that dementia was caused by many factors, was in contrast with the explanation used by a contemporary French physician Antoine Laurent Jessé Bayle (1799–1858).  Bayle view was that dementia was caused by an organic disease that caused swelling in the brain. Unknown at the time, Bayle was referring to the effect of long term syphilis infection. Bayle also observed that dementia progresses and becomes increasingly more severe. This interpretation was so influential at the time that dementia was also called Bayle’s disease and dementia paralytica.

By the late 1800s, French physicians already started engaging in a discussion about different types of dementia and identifying senile dementia, the initial observation of a biological cause of dementia, and the progressive nature of the disease.

German Scientists
While this discourse was going on, there was a parallel push to study dementia in Germany. The German scientists had a slightly different approach, including attracting a different name. Senile dementia was named as Presybyophrenia—from the Greek Presby meaning “old” and phrenia meaning of the “mind”—dementia of older age. This term was coined by the German physician Karl Ludwig Kahlbaum (1828–1899). With his associate Ewald Hecker (1843–1909), Kahlbaum introduced a classification system that applies terms that described the disease as expressed depending on biological developments in the body. These German physicians concentrated on nosology—how diseases are categorized. Their observations and methods have contributed to how we categorize disease today.

They argued that by grouping mental disorders based on how they are expressed ignores how the diseases progresses and how it affects the person. Supporting Pinel-Esquirol-Bayle contention that the cause of the disease should be the defining feature of the disease.  For example, a fever that comes on in a day and dissipates in a few days is very different from a fever that comes on slowly and lasts longer. Differences in how a disease progresses and the eventual outcome as a method of classifying different diseases proved providential. Kahlbaum and Hecker’s evaluation of earlier classification of diseases was that physicians were often prejudiced. By making judgements on how diseases are similar to each other, prevented physicians from gaining useful insights into its causes and how to address treatment.

There was a convergence between the French and German physicians at the turn of the 20th century. At the time the final stages of the bacterial infection of syphilis that results in dementia—neurosyphilis—was contributing to between 10-24% of all hospitalized mental health patients at the time. This is what led Bayle to identify physical causes of dementia but did not know that it was syphilis. In fact, Alois Alzheimer’s specialization—and how he met his wife, the widow of one of his patients—was as an expert in treating syphilis. In 1910, Alzheimer already knew of the connection between syphilis and the plaques and tangles that came to characterize his disease. This biological cause encouraged further parallels between an infection and senile dementia.

But both Kahlbaum and Hecker were moving away from simplistic explanations of diseases. Together with Emil Kraepelin (1856-1926), who later coined Alzheimer’s disease, these three men also shared a deep skepticism for the localization of behavior in the brain. Such brain explorations were becoming very popular during the latter half of the 19th century. Paul Broca (1824-1880) together with Carl Wernicke (1848-1905) were leading pioneering work on the localization of brain functions, specifically in speech. But Kahlbaum-Hecker-Kraepelin had bigger worries than such collegial competition.

The 1900s saw an explosion of academic proliferation. Some of the most famous scientists at the time included: Max Planck (quantum physics), Albert Einstein (physics), Marie Curie (X-rays), Sigmund Freud (psychoanalysis), Niels Bohr (physics), Ivan Panlov (medicine/psychology), Santiago Ramón y Cajal (neuroscience), Franz Boas (anthropology), Wilhelm Wundt (experimental psychology), Richard J. Ussher and Robert Warren (zoology), Ferdinand von Zeppelin (aeronautics) among many other. Together with the new science fiction of H. G. Wells, the early 1900s saw a proliferation of academic disciplines and new hope for the scientific method.

For the emerging study on dementia and the newly identified Alzheimer’s disease by Emil Kraepelin there were other considerations. Primarily there was the perceived (and real) threat that psychiatry was facing from psychoanalysis and from psychology. The case in point was the story of Anna O, now known as Bertha Pappenheim (1859–1936), whose psychoanalytic “cure” created fervor and excitement. An Austrian-Jewish feminist, Bertha Pappenheim suffered from hysteria—paralysis, convulsions, hallucinations and loss of speech—without apparent physical cause. Josef Breuer ostensibly succeeded in treating Anna by helping her to recall forgotten memories of traumatic events. Psychoanalysts proposed that physical symptoms are often the surface manifestations of deeply repressed conflicts. At the turn of the 1900s, after centuries of treating madness as a mystical curse, here was a clear answer and a clear solution. After distinguishing idiocy, epilepsy and cretinism, the remaining maladies had the possibility of being psychosomatic. In hindsight, we now know that these particular case studies—including Bertha Pappenheim—were not cured, and the likely cause of these expressions of hysteria were biological in nature.

In addition to the new vogue of psychoanalytic models, there was a complementary interpretation of disease championed by Kraepelin’s own mentor, Wilhelm Wundt. Kraepelin submitted his thesis on "The Influence of Acute Illness in the Causation of Mental Disorders" under Wundt, for which he received his medical degree in 1878.  A year later Wundt founded the first formal laboratory for psychological research at the University of Leipzig. Wundt and experimental psychologists promoted the idea that we learn how to behave, including when we are behaving abnormally, a theory very much in keeping with the psychoanalyst’s view of disease. At the turn of the century in Germany, psychological theories were becoming the new norm. Kraepelin and his staff did not approve of this interpretation of mental illness. Max Isserlin, an assistant to Kraepelin, made disparaging remarks about psychoanalyses being “complex mythology” which Freud identified as arguments coming “from the blackest clique in Munich,” referring to Kraepelin’s clinical staff. Such animosity ultimately lead to Isserlin being personally expelled by Jung in 1910, from the Congress of the Psychoanalytical Association in Nuremberg. Despite such obvious animosity, there was an intellectual challenge as well. While psychologists and psychoanalysts repeatedly believed that they were gaining ground in understanding mental diseases, what did psychiatry have to offer?

Kraepelin, a seasoned administrator, was aware of this constant yearning for answers. Yearnings for a panacea were real. Kraepelin needed to distinguish psychiatry from the “learning” of the psychologists and the “unconscious” of the psychoanalysts. In doing so he had to resort back to the biology of mental illness. Psychiatry could contribute the biological aspect of mental health.

The contribution of Biology
Kraepelin (with Eugen Bleuler) gained a different kind of success by differentiating schizophrenia from a variety of mental disorders.  The 1880 U.S. Census only distinguished seven categories of mental illness: mania, melancholia, monomania, paresis, dementia, dipsomania, and epilepsy. Psychosis was categorized as hysteria, melancholy, mania, and paranoia. Within this morass of disorders, Kraeplein differentiated between premature (praecox) dementia (schizophrenia) and ‘manic depression’ as two separate forms of psychosis. Although schizophrenia was already described as dementia praecox, first in 1852 by the French physician Bénédict Morel and later in 1886 by Heinrich Schule, it was Arnold Pick in 1891 who defined schizophrenia as a psychotic disorder (hebephrenia from the Greek hebe “young,” and phrenia “mind”). In 1911, Eugen Bleuler revised this idea, renaming ‘dementia praecox’ (premature dementia) as schizophrenia. 

Kraepelin reverted back to the earlier French scientists Pinel-Esquirol-Bayle in arguing for a biological cause to schizophrenia by anatomical or toxic processes (as yet unknown.) When, on his second attempt, Alzheimer managed to publish his observations on Auguste Deter, Kraepelin jumped at the chance to reinforce the biological emphasis of disease by elevating Alzheimer’s disease as different from senile dementia. As with schizophrenia Kraepelin was intimating that Alzheimer’s disease is caused by anatomical or toxic processes which are yet unknown.

Fast forward to 2017, with increasingly powerful biological tools that are now available we are about to enter this portal that was created more than a century ago.

Alzheimer’s disease guidelines published in 2011 by the U.S. National Institute on Aging and Alzheimer Association, has attempted to define how biological measures can be usefully classifying mental diseases. As with the early pioneers Kahlbaum, Hecker, and Kraepelin, a new method is being devised to better answer the question of what dementia is.  Current psychiatric classification of diseases—Diagnostic and Statistical Manual (DSM-5) and International Classification of Disease (ICD-10)—are focused on being reliable but are short on validity. Repeating the conflict between the early German and French scientists more than a hundred years ago, there is now a shift from surface expression of the disease to search for the underlying causes, except now we can measure biological indicators better than in the past.

To enable this biological emphasis, and in contrast to the DSM-5 and ICD-10, a new classification criterion is being promoted. Research Domain Criteria (RDoC) is a new classification of diseases initiated by the U.S. National Institute of Mental Health director Thomas Insel. Insel now works for Google Life Sciences with a new name: Verily, a for-profit health company. RDoC argues that mental disorders are biological disorders involving brain circuits. And the first test of RDoC’s approach is with dementia. Mirroring Bayle’s 1882 contention that inflammation of membranes that surround the brain and the spinal cord resulted in mental disease, RDoC is following a long line of psychiatrists looking for biological markers to mental health.

Biological determinism of dementia.
There are many faults with RDoC’s focus on neural circuits which excludes research on psychological processes and mechanisms. This is nothing new and we only have to see the arguments in the late 1800s to understand these criticisms. For example, Bayle’s colleagues, especially Esquirol, argued that although there might be correlation there is no indication of causation. Even if causation can be identified it does not explain all dementias. And there are other concerns that were voiced earlier on in the history. Especially by Erich Hoche (1865-1943) on our inability to accurately identifying mental disease; Karl Birnbaum (1878-1950) on how disorders are expressed differently by individuals or cultures; Robert Gaupp (1870-1953) on psychosomatic factors that involve mental, emotional, or behavioral factors. And of course, we now know that that these criticisms remain valid to this day. RDoC simple brushes them away, not by ignoring these factors, but by discounting their influence and importance. It succeeds in doing this because it is concentrating on dementia.

We still do not know what dementia is. The basic issue is a catch 22—in order to be able to differentiate diseases we need to understand their causes and to understand the causes we need to be able to differentiate it. We must be aware of the history in order to stop this cycle of oscillating between the false dichotomy of biological vs everything else. Normality is not simply the absence of pathology. Many symptoms exist on a spectrum or continuum from mild expressions that might be viewed as variants of normality through to severe symptoms associated with impairment. One way to escape this conundrum is to ignore the expression of the disease and to accept the underlying “cause” as proof. But what RDoC ignores is that there are many biological markers and that the brain is the most complex entity in the universe. In such circumstance then you have to approach dementia as a public health issue, where many causes are present. An approach which RDoC continues to ignore. Could it be because  you cannot commercialize public health?

Engstrom, E. J. (2016). Tempering madness: Emil Kraepelin’s research on affective disorders. Osiris, 31(1), 163-180.
Garrett, M. D., & Valle, R. (2015). A New Public Health Paradigm for Alzheimer’s Disease Research. SOJ Neurol, 2(1), 1-9.
Kendler, K. S., & Engstrom, E. J. (2016). Kahlbaum, Hecker, and Kraepelin and the transition from psychiatric symptom complexes to empirical disease forms. American Journal of Psychiatry, appi-ajp.
Kurt, C.S. et al., The Realities of Ageing, Boston, 1990.
Wundt, W. (1881). Wilhelm Wundt to Emil Kraepelin, 23 January 1881. Max Wundt Papers: University of Tübingen Archives, 228, 17.

© USA Copyrighted 2017 Mario D. Garrett