Correlated decline of cognitive and motor phenotypes and ADRD pathologies in old age

Abstract

Introduction: Examining motor and cognitive decline in separate models may underestimate their associations.

Methods: In a single trivariate model, we examined the levels and rates of decline of three phenotypes, sensor-derived total daily physical activity, motor abilities, and cognition in 1007 older adults during 6 years of follow-up. In 477 decedents, we repeated the model adding fixed terms for indices of nine brain pathologies.

Results: Simultaneous rates of decline of all three phenotypes showed the strongest correlations with shared variance of up to 50%. Brain pathologies explained about 3% of the variance of declining daily physical activity, 9% of declining motor abilities, and 42% of cognitive decline.

Discussion: The rates of declining cognitive and motor phenotypes are strongly correlated and measures of brain pathologies account for only a small minority of their decline. Further work is needed to elucidate the biology underlying correlated cognitive and motor decline in aging adults.

Keywords: aging; cognition; motor abilities; neuropathology; physical activity.

Figure 1.. Simultaneous decline of cognition, motor abilities and total daily activity.

Upper Row (A-C) show the longitudinal trajectories of repeated measures of cognition (A) motor abilities (B) and total daily physical activity (C) during the study. Crude longitudinal trajectories of repeated measures of each of the three phenotypes (gray lines) and mean paths of decline predicted for each phenotype (black lines). Middle Row (D-F) shows the inter-relationship between the slopes extracted from a single trivariate model that examined the simultaneous rates of change for the three phenotypes. Each panel in the row shows a scatter plot of participants based on their person-specific rate of change (slope) in a pair of the examined phenotypes (black circles) and a regression line (blue) is superimposed on each of the three panels. D shows the slopes of cognitive decline (X axis) and motor decline (Y axis); E shows the slopes of cognitive decline (X axis) and total daily activity and F shows the slopes of declining daily activity (X axis) and motor decline (Y axis). Bottom Row (G-I): Using standardized slopes, the bottom row extends the associations illustrated in the middle row to show the extent of discrepancy between the three pairs of slopes. Slopes were considered non-discrepant if the pair of slopes was within 1 SD of one another (green). Slopes were discrepant their slopes were greater than 1 SD (blue) or less than 1 SD (red). As in the middle row, G) shows the slopes of cognitive-motor decline (CM); H shows the slopes of cognitive-daily physical activity decline (CA); I shows the slopes of motor-daily physical activity decline (MA). About 80% (n=775, 77%) showed non-discrepant slopes.

Figure 2.. Frequency of slow and fast cognitive decline with motor decline e.

To visualize the inter-relationship of declining cognition and both motor phenotypes, we stratified the rates of decline based on slopes above or below the median rate of decline for each of the three phenotypes. Since the two motor slopes might vary from one another, we defined three patterns of motor decline. Fast motor decline was present if both rates of motor decline were below the median; slow motor decline was present if both rates of decline were above the median; intermediate motor decline was present if one phenotype was below and the other was above their median rate of decline. Most adults with faster cognitive decline, showed faster decline of both motor phenotypes. While, most older adults with slower cognitive decline also showed slower motor decline, a larger percentage showed discrepancies between the rates of slow cognitive decline and motor decline.

Figure 3.. Variance of declining cognitive, motor abilities and daily physical activity accounted for by ADRD brain pathologies.

This figure summarizes the additional variance of decline explained by the measures of nine brain pathologies (blue) as compared to a model with demographic measures age, sex, and education and their interaction with the annual rate of change alone for each of the three phenotypes. The majority of decline especially for motor phenotypes remained unexplained.