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Neurobiol Aging. 2018 Jan;61:138-145. doi: 10.1016/j.neurobiolaging.2017.08.029. Epub 2017 Sep 5.

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

Author information

1
Department of Psychiatry and Neuropsychology, Alzheimer Center Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands. Electronic address: willemijn.jansen@maastrichtuniversity.nl.
2
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA; Department of Behavioral Sciences, Rush University Medical Center, Chicago, IL, USA.
3
Department of Psychiatry and Neuropsychology, Alzheimer Center Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands; Department of Neurology, VUmc Alzheimer Center, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
4
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Pathology, Rush University Medical Center, Chicago, IL, USA.
5
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA; Department of Pathology, Rush University Medical Center, Chicago, IL, USA.
6
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA.
7
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
8
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Behavioral Sciences, Rush University Medical Center, Chicago, IL, USA.

Abstract

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 transactive response DNA-binding protein 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 transactive response DNA-binding protein 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.

KEYWORDS:

Aging; Cognitive decline; Dementia; Mixed-effects change point model; Neuropathologies

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