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Ann Clin Transl Neurol. 2019 Sep 30. doi: 10.1002/acn3.50857. [Epub ahead of print]

Common age-related neuropathologies and yearly variability in cognition.

Yu L1,2, Wang T1,2, Wilson RS1,2,3, Leurgans S1,2,4, Schneider JA1,2,5, Bennett DA1,2, Boyle PA1,3.

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Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois.
Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois.
Department of Psychiatry and Behavioral Sciences, Rush University Medical Center, Chicago, Illinois.
Department of Preventive Medicine, Rush University Medical Center, Chicago, Illinois.
Department of Pathology, Rush University Medical Center, Chicago, Illinois.



Cognitive variability is a potentially important source of heterogeneity in longitudinal cognitive profiles. We examined the extent to which common age-related neuropathologies including Lewy bodies and Alzheimer's disease (AD) contribute to yearly variability in late life cognition.


Data came from 1321 community-dwelling older adults who were followed annually for up to 23 years, died and underwent brain autopsy. Cognition was assessed via a comprehensive testing battery. Uniform neuropathologic evaluations assessed burdens of Lewy bodies, AD, infarcts, TDP, hippocampal sclerosis, amyloid angiopathy, atherosclerosis, and arteriolosclerosis. Using mixed effects models, yearly variability in cognition, characterized as within-person variability of annual cognitive scores, was regressed on the nine neuropathologic indices.


The average age of decedents was 90 years and 69% were female. At autopsy, about two thirds met the pathologic criteria for AD. Neocortical Lewy bodies were present in 13% of the individuals. Other neuropathologic conditions also were common. All neuropathologic indices except for microinfarcts were associated with cognitive decline. Individuals with neocortical Lewy bodies had almost twice the yearly variability in cognition compared to those without. Individuals with AD had about 70% more variability compared to those without. Yearly variability was present among persons with vascular diseases but to a lesser degree than neocortical Lewy bodies and AD.


Lewy body pathology is associated with pronounced variability in annual cognitive assessments but this finding is not unique to this pathology. Comparable variability is present among persons with AD pathology and to a lesser extent among persons with cerebrovascular pathologies.

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