ABSTRACT
Objective
To test the hypothesis that Alzheimer's disease and related neuropathologies contribute to the association between hospitalization and cognitive decline in old age.
Methods
As part of a longitudinal clinical‐pathologic cohort study, 526 older persons (mean age at death=90.9, 71% female) without dementia at baseline completed annual cognitive testing and were autopsied at death. Hospitalization information was obtained from linked Medicare claims records. Neuropathologic examination assessed β‐amyloid burden, tau tangle density, neocortical Lewy bodies, hippocampal sclerosis, chronic gross and microscopic cerebral infarcts, and TDP‐43.
Results
Over mean 5.1 years, a total of 1,383 hospitalizations occurred and the mean annual rate of hospitalization was 0.5 (SD=0.6; median=0.4). Higher rate of hospitalizations was not directly related to higher burden for any of the neuropathologic markers. Higher rate of hospitalization was associated with more rapid cognitive decline (estimate=‐0.042, SE=0.012, p<0.001), and after controlling for all 7 neuropathologic markers, the association was essentially the same (estimate=‐0.040, SE=0.013, p=0.002). In a multivariable model with three‐way interactions of neuropathologic markers with hospitalization rate and time, the association between hospitalization rate and faster cognitive was greater in persons with more tangle pathology (estimate for interaction= ‐0.007, SE=0.002, p=0.002) and in persons with neocortical Lewy bodies (estimate for interaction=‐0.117, SE=0.042, p=0.005).
Interpretation
Older persons with more hospitalizations experienced faster rates of cognitive decline, and this association was more pronounced in persons with more tau tangle density and with neocortical Lewy body pathologies.
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