An exploration of the latest findings about Alzheimer's Disease.

Posted Nov 19, 2013

Review of The Alzheimer Conundrum:  Entanglements of Dementia and Aging.  By Margaret Lock.  Princeton University Press.  310 pp.  $29.95

In 2010 at least 35.6 million people throughout the world were living with dementia.  Experts estimate that the number is likely to double every twenty years, to 65.7 million in 2030 and 115.4 million in 2050.  The cost of caring for them, which now exceeds $600 billion, is expected to increase by 85% in 2030.  The burden on families, health care systems, governments, and the global economy may well be unsustainable.

Despite considerable investments in medical research in the last few decades, Margaret Lock, a professor emerita in the departments of Social Studies of Medicine and Anthropology at McGill University, points out, scientists have been unable to discover the causes of Alzheimer’s Disease, the most common form of dementia, or design effective treatments, let alone a cure.

In The Alzheimer Conundrum, Lock explains the latest findings in neuropathology and genetics about Alzheimer’s and enters into the debates about next steps.  The challenge for researchers is especially difficult, she emphasizes, because they have been unable to separate general claims from “the dirty particulars” of each case, which include individual complexity, plasticity, and adaptability to new environments, toxins, and other external factors.  Sharply critical of the views that “normal” aging and dementia can be disentangled and that Alzheimer’s can be wiped out as if it were as infectious disease, Lock makes the claim that an approach oriented primarily to prevention and cure through surveillance of biomarker genes, amyloid plaques and tangles and the development of drugs to counter their impact is “reductionist.”  It has the unintended consequences, she suggests, of side-lining socioeconomic, political, and public health risk-reducing initiatives and discouraging studies of why and how so many old folks remain healthy and active.

Comprehensive, cogent, and densely detailed, The Alzheimer Conundrum provides a useful antidote to media hype about “silver bullets” that are “just around the corner” and makes an important contribution to our understanding of an achingly tragic disease that touches virtually all of us.

Lock does not hesitate to offer controversial assessments of the significance of recent research.  She acknowledges, for example, that deposits of amyloid plaque on the brain are implicated “in some way” in dementia-like conditions.  It is less clear, she asserts, whether these deposits are a cause or even a trigger of Alzheimer’s.  At autopsy, many elderly adults who score very well on neuropsychological tests (including the much-studied nuns of the School of Sisters of Notre Dame) exhibit extensive neurofibrillary tangles and senile plaques.  The amyloid cascade hypothesis, Lock notes, has been further “battered and bruised” by the failure of drugs that retard the development of plaque to improve cognition.  The hypothesis “hangs on,” but it appears to be “urgently in need of modification or retirement.”

And Lock cautions against “geneticization,” the inheritance-is-destiny phenomenon in which differences between individuals are “reduced to their DNA codes.”  Genes have actually been demoted, she writes.  Most scientists now acknowledge that they are not stable, “do not, on their own, determine either individual phenotypes or the biological makeup of future generations,” and that many factors, “including events internal and external to the body, enhance or inhibit gene expression.”

An allele of the APOE gene, for example, has been identified as an important, albeit imperfect, risk marker for Alzheimer’s.  But given questions about the extent of the risk, evidence of the heterogeneity of human brains, and the absence of effective treatments, physicians and clinicians, according to Lock, lack the paradigms and the vocabulary to assess “susceptibility genotyping” and make use of “probabilistic information.”  Further complicating the utility of predictive testing, of course, is the possibility of discrimination by employers and insurers if the results become public.

The Alzheimer Conundrum
is best understood as a snapshot, taken at a time in which research on dementia is at a crossroads.  Filled with information and a cacophony of opinions, the book stimulates skepticism, even about Lock’s claims.  Is the amyloid cascade hypothesis “past its due date”?  Will tests of families from Antioguia, Colombia, who carry the gene presenilin-1 and often exhibit memory loss that progresses to dementia when they reach their 50’s, shed light on “common Alzheimer’s?”  Most important, perhaps, is it, indeed, impossible to disentangle dementia and aging?

What The Alzheimer Conundrum does make clear is that in the absence of a breakthrough we have an urgent need to move beyond platitudes – get plenty of exercise, lose weight, eat wisely, and complete crossword puzzles – and formulate robust public policies to help us stave off, slow down, and deal with this most dreaded of diseases.

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