Brain pathology contributes to simultaneous change in physical frailty and cognition in old age

Abstract

Objective: First, we tested the hypothesis that the rate of change of physical frailty and cognitive function in older adults are correlated. Next, we examined if their rates of change are associated with the same brain pathologies.

Methods: About 2,167 older adults participating in the Religious Orders Study and the Rush Memory and Aging Project had annual clinical evaluations. Bivariate random coefficient models were used to estimate simultaneously the rates of change in both frailty and cognition, and the correlation of change was characterized by a joint distribution of the random effects. Then, we examined whether postmortem indices from deceased were associated with the rate of change of frailty and cognition.

Results: During an average follow-up of 6 years, frailty worsened by 0.09 unit/y and cognition declined by 0.08 unit/y. Most individuals showed worsening frailty and cognition (82.8%); 17% showed progressive frailty alone and <1% showed only cognitive decline. The rates of change of frailty and cognition were strongly correlated (ρ = -0.73, p < .001). Among deceased (N = 828), Alzheimer's disease pathology, macroinfarcts, and nigral neuronal loss showed independent associations with the rate of change in both frailty and cognition (all ps < .001). In these models, demographics explained about 9% of the variation in individual rate of change in frailty, and neuropathologies explained about 8%. In contrast, demographics and neuropathologies accounted for 2% and 30%, respectively, of the variance in the cognitive decline.

Conclusion: The rates of change in frailty and cognition are strongly correlated and this may be due in part because they share a common pathologic basis.

Keywords: Aging; Brain pathology.; Cognition; Physical frailty.

Figure 1.

Change in frailty and cognition and the effect of more brain pathology on their rates of change. The left panels show change in frailty (top) and global cognitive function (bottom) during the study. Crude paths of change (gray lines) and mean paths of change predicted by the model (black lines) in frailty (top) and global cognitive function (bottom). The right panels show the predicted paths of frailty (top) and cognition (bottom) for four participants with increasing burden of brain pathology. (1) Black line, the predicted path for a participant with low level of Alzheimer’s disease (AD) pathology (10th percentile). (2) Red line, the predicted path for a participant with a high level of AD pathology (90th percentile). (3) Green line, the predicted path for a participant with a high level of AD pathology (90th percentile) and macroinfarcts. (4) Blue line, the predicted path for a participant with a high level of AD pathology (90th percentile), macroinfarcts and severe nigral neuronal loss.

Figure 2.

Annual rates of change in frailty and cognition. On the left is a two-dimensional histogram of annual rates of change in frailty and cognition estimated by simultaneous random effects model. The figure on the right depicts the density of the number of participants shown in the two-dimensional histogram with black showing increased density compared with the lighter shades of gray.