Thursday, April 11, 2019

A New Old View of Alzheimer’s Disease



 An article this week by Gina Kolata, the longtime science and health writer for the New York Times, described an emerging recognition that our view of Alzheimer’s disease may be incorrect.  The prevailing view going back to the 1980s is that Alzheimer’s disease is a distinct disorder characterized by amyloid plaques and neurofibrillary tangles.  Although there has always been mention in the research literature of cases with mixed pathologies, for example, characteristics of Alzheimer’s disease and vascular dementia, these cases were dismissed and efforts to understand and, particularly, to treat Alzheimer’s disease were based on the assumption that there was a pure type of plaques and tangles.  Instead, recent studies have documented that people with multiple pathologies are quite common and represent the norm, rather than the exception.  These other pathologies are found in Parkinson’s disease, Lewy-Body Dementia, Fronto-temporal Dementia, vascular dementia, and other syndromes.  And likewise, patients with those disorders often have evidence of plaques and tangles.  In other words, Alzheimer's is part of a continuum, rather than a distinct entity, except perhaps for the genetically driven early onset cases.

This is in some ways an old view of Alzheimer’s.   Early researchers, such as Sir Martin Roth, suggested that dementia occurred when the accumulation of brain damage passed a threshold.  The more different sources of damage, the more likely the threshold would be crossed.  

Why does this matter? As Kolata and others have written, the effort to treat Alzheimer’s disease with medications that dissolve amyloid plaques has not been successful.  One reason for the failure may be that plaques are only part of the pathology in many patients. Other treatment approaches could well founder on trying to treat one pathology without taking into account other pathologies. This more heterogeneous view of dementia also puts preventive efforts in a different perspective.  Potential protective factors such as a specific food or diet, type of exercise, or other lifestyle factors may not affect the various risks for these pathologies in the same way.  More broadly, there is a need to re-examine the hypothesis that amyloid drives the deterioration process, and to consider alternative pathways that takes into account the other common pathologies.

Two groups have contributed to the acceptance of the homogenous view of Alzheimer’s disease.  The first is the Alzheimer’s Association.  As some of you may remember, the Alzheimer's Association, when founded by five grassroots community organizations, was known as the Alzheimer’s Disease and Related Disorders Association (ADRDA) and reached out broadly to everyone with dementia.  That name was a mouthful, however, and so the Association undertook a “rebranding” process with a new name and emphasis on Alzheimer’s. The rebranding gave the Association a simpler message for attracting donors and winning government support.  And it was very successful.  The growth in public recognition and research support has been tremendous.  But the simple message of a single disease may have influenced researchers to ignore the genetic, symptomatic and pathological heterogeneity that characterize cases of Alzheimer's.

The other group that has pushed a homogeneous view of Alzheimer’s disease is the pharmaceutical industry.   Drug trials have generally been designed to assess benefits on a broad sample of persons with dementia, and have not considered factors such as genetic risks or other indicators of heterogeneity.  The search for the broadest possible market may be good business but it is not good science.

In a 2018 paper in the journal, Brain, two British researchers, Elizabeth Coulthard and Seth Love, suggest moving beyond broad but imprecise diagnostic terms and instead classify patients according to the pathology present. That certainly makes sense for research, where experimental treatment could be tailored more specifically to the pathologies present.  

Another advantage of a broader conceptualization of dementia is that it could lead to a renewed emphasis on support and care for patients and their family caregivers.  Taking the simple view, researchers, advocates and drug companies have been promising that they will end Alzheimer’s disease if only there is enough money for research.  Hopefully, there will be breakthroughs, but the obstacles to development of an effective treatment may be considerable and are likely to occur in small steps.  In the meantime, there needs to be more creative effort to provide high quality and humane care for people with the disease and support for their family members.  And this help needs to be available to the broad spectrum of people with dementia.

The photo is Brontë House in Yorkshire, England.

Link to Gina Kolata, “The Diagnosis Is Alzheimer’s. But That’s Not the Only Problem,” The New York Times.  https://www.nytimes.com/2019/04/08/health/alzheimers-dementia-stroke.html

Reference:  Coulthard, E. J., & Love, S. (2018).  A broader view of dementia: Multiple co-pathologies are the norm.  Brain, 141, 1894-1897.  Doi:10.1093/brain/awy153