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Abstract

Background: It is hard to test the role of Alzheimer pathology in man. Alzheimer himself believed that the pathology he described was epiphenomenal, but removing it is the basis of current therapeutic strategies. Most people with late-onset dementia have mixtures of pathologies. Analyzing interactions of Alzheimer pathology with co-existing pathologies presents an opportunity to test if it is detrimental. Surprisingly, published data show (mostly unreported) antagonism between Alzheimer and other pathologies. Methods: Appropriate statistical methods were used to disentangle the contributions of five degenerative pathologies (Alzheimer, vascular, Substantia Nigra degeneration, Lewy Bodies, Fronto-temporal lobar degeneration) or inflammatory markers to three clinical outcomes (cognitive decline, neuropsychiatric symptoms and survival). Specifically, I tested if (a) adverse effects of different pathologies were simply additive, synergistic or antagonistic and (b) Alzheimer pathology showed non-linear associations with outcomes. Results: Alzheimer pathology (a) antagonized adverse effects of every other pathology or inflammatory index on most outcomes and (b) showed an inverted-U relation to survival. Conclusions: In line with published data, Alzheimer pathology antagonized adverse effects of every observed non-Alzheimer pathology or inflammatory marker with which it coexisted. This ubiquitous antagonism was unique to Alzheimer pathology. Moreover, its inverted-U relation with survival is typical of a physiological marker, not a pathological one. Together, these results imply that Alzheimer pathology may be generally protective, so removing it may be unhelpful. Further studies should test if Alzheimer pathology antagonizes further factors that adversely affect brain function.

Biography

Jonathan Williams qualified as a physician from Cambridge and Birmingham Universities before completing his Ph.D. in Experimental Psychology at Oxford. He then trained in psychiatry and undertook postdoctoral studies that intercalated clinical and academic work at Oxford, including 10 years at The Oxford Project to Investigate Memory and Ageing (OPTIMA). He now works as a consultant in Psychiatry of Older Adults in Hamilton, New Zealand. He has published 40 refereed papers.