Abstract
Neuroimaging studies have shown that the association between mobility and cognition with aging is based on a shared neuropathology and can be explained in part by fitness maintenance. However, the temporal sequence between fitness, neuropathological changes, and mobility loss have not been fully evaluated. 332 participants of the BLSA aged 60 and older, initially free of cognitive and mobility impairments, with repeated measures of fitness (400m time), mobility (6m gait speed), and global and regional neuroimaging markers over 4 years. Neuroimaging markers included volumes of total brain, ventricle, as well as major regions from frontal, parietal, medial temporal, subcortical motor areas, and corpus callosum. Autoregressive models were used to examine the temporal sequence between fitness, volumes in each ROI, and mobility performance, after adjustment for baseline age, sex, race, body mass index, height, education, intracranial volume, and APOE ɛ4 status. After adjustment, greater volumes of total brain and selected frontal and parietal areas, entorhinal cortex, and corpus callosum were unidirectionally associated with future faster gait speed over and beyond cross-sectional and autoregressive associations. Faster gait speed predicted future greater hippocampus and precuneus. Higher fitness was unidirectionally associated with future greater parahippocampal gyrus, and not with volumes in other areas. Smaller ventricle predicted future higher fitness. Volumes of selected cortical areas and corpus callosum may be early predictors of future mobility, and mobility performance also indicates future hippocampus and precuneus. Maintaining fit may preserve future parahippocampal gyrus, while ventricle may determine future fitness level.