Hospitalization, Alzheimer's Disease and Related Neuropathologies, and Cognitive Decline

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 years, 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 transactive response DNA binding protein 43 kDa. RESULTS: Over a mean of 5.1 years, a total of 1,383 hospitalizations occurred, and the mean annual rate of hospitalization was 0.5 (standard deviation = 0.6, median = 0.4). Higher rate of hospitalization 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, standard error [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 3‐way interactions of neuropathologic markers with hospitalization rate and time, the association between hospitalization rate and faster cognitive decline 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. ANN NEUROL 2019;86:844–852