Age and the association of dementia related pathology with trajectories of cognitive decline

Publication date: Available online 5 September 2017
Source:Neurobiology of Aging
Author(s): Willemijn J. Jansen, Robert S. Wilson, Pieter Jelle Visser, Sukriti Nag, Julie A. Schneider, Bryan D. James, Sue E. Leurgans, Ana W. Capuano, David A. Bennett, Patricia A. Boyle
The association of dementia related pathologies with cognition is hypothesized to decrease as age advances. We examined this in 413 persons without cognitive impairment at baseline who completed annual cognitive evaluations during a mean of 10.4 years. After death, neuropathologic examinations quantified beta-amyloid plaque load, neurofibrillary tangles, and TDP-43 pathology, and identified Lewy bodies, hippocampal sclerosis, and gross and microscopic cerebral infarcts. We tested whether age at death modified associations of these neuropathologies with the nonlinear trajectory of cognitive decline using mixed-effects change point models. The rate of global cognitive decline was gradual at first and then increased approximately 10-fold in the last 3 years of life. After adjustment for all other pathologic indices, tangle density, gross infarcts, Lewy bodies, and TDP-43 were associated with global cognitive decline. However, the deleterious association of dementia related pathologies with cognitive decline did not systematically vary by age. This suggests that the neuropathologic mechanisms underlying late-life cognitive decline do not substantially differ across the spectrum of age.



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