An Anthropologist Surveys Alzheimer’s Disease

An Anthropologist Surveys Alzheimer’s Disease
A review of “The Alzheimer Conundrum: Entanglements of Dementia and Aging” by Margaret Lock. Princeton University Press, 2013.

by Guest Blogger,
Tyler Kokjohn, Ph.D.

Ignoring well-founded, but unwelcome criticism? – BAD IDEA.

I wonder what Dr. Lock was thinking when she published this book. It is not a light read and a bit depressing, so it doesn’t look like a future best seller. Worse, as a stinging indictment of the current efforts to comprehend and combat Alzheimer’s disease (AD), it seems almost guaranteed to alienate many of the research community movers and shakers.

The book distills Dr. Lock’s long-term and richly detailed study of the dauntingly complicated subject of AD. After deep immersion in the primary research publications and extensive interactions with leading investigators, this remarkable outsider comprehends the nuances of AD as well as the experts. Several of her conclusions regarding the origins, diagnosis and management of dementia diverge radically from the current AD research community mainstream consensus.

Dr. Lock exposes the uncomfortable fact that research has yet to reveal the definitive biochemical mechanism(s) for AD dementia production. And she asks some tough questions. An age associated condition, could dementia be an inextricable consequence of the aging process itself? Is the current presumed prime therapeutic target, deposits of sticky proteins in the brain termed amyloid, the key to a cure or merely a correlated, deceptive side effect of another underlying disease process? The ‘amyloid cascade hypothesis’ has long been the unifying focus of AD research and Dr. Lock questions whether we are actually looking at the right things or getting the whole complex interplay of aging, environment and dementia in proper context. Her blunt assessment of the situation and unvarnished presentation of her conclusions may seem like pure poison to some.

394px-AD_versus_CO%20HersenbankThe suggestion that Alzheimer’s disease may not even be a disease is definitely going to fall on some deaf ears for a while. Enormous amounts of money, effort and even some lives have already been invested pursuing amyloid deposits as the principal culprit in dementia. And more difficult, time consuming and enormously expensive human trials are now underway. Many have expressed misgivings concerning the amyloid cascade hypothesis and how it dominates AD research and mitigation strategies, but I wonder if the antidote to Dr. Lock’s impertinent challenge will be impressive silence.

I do not agree with all of Dr. Lock’s assertions and conclusions, but believe that ignoring her book would be a terrible mistake. New clinical trials are now underway in which amyloid disrupting interventions will be administered well before dementia appears. The subjects participating in these trials will harbor rare genetic mutations that produce an early onset AD dementia, enabling investigators to neatly bypass the problems of diagnosis and other uncertainties that confounded previous studies. If these early intervention trials delay the predicted onset of dementia it would provide critical evidence supporting the amyloid cascade hypothesis and suggest that AD is a treatable, perhaps ultimately curable, age associated disease. In that event, we must temper justified euphoria with the recognition that applying such preventative therapies to the many millions at risk for AD will demand overcoming daunting financial and logistical challenges. Dr. Lock’s thoughts on the biochemical diversity of dementia and how the interplay between genes, environment and behavior influences the risk of cognitive failure may be critical for the successful, real world mitigation of AD.

For now, the work continues on schedule and we await the results. But what if these new trials fail? If that should come to pass, I hope my colleagues remember Dr. Lock’s book. And return when the time and environment are right.

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