Individuals with MCI Exhibit Stronger Posterior Functional Connectivity than Healthy Elders after a 12-week Walking Intervention

Abstract

PURPOSE: Functional resting state networks are disrupted in Mild Cognitive Impairment (MCI) and Alzheimer’s disease (AD), leading to an eventual disappearance of functional connections in posterior regions and increased connectivity in frontal regions as compensation for neuronal damage. Physical activity appears to delay the onset of AD, but it is unknown if exercise training alters resting state brain networks in MCI. We investigated the effects of a 12-week treadmill walking intervention on resting state brain networks in MCI and healthy elders. METHODS: Functional MRI (fMRI) was acquired at rest before and after a supervised 12-week treadmill walking exercise intervention in 16 MCI and 16 healthy elders. Time series fMRI data were extracted from 116 5mm spheres surrounding center of gravity coordinates in each parcellation of the Automated Anatomical Labeling (AAL) atlas. Correlation matrices (116 x 116) were constructed and the null distribution was calculated from 10,000 permutations. Differences between groups and across time in correlation coefficients were determined using repeated measures ANOVA [FDR correction p<0.05]. RESULTS: Healthy elders decreased connectivity between rolandic operculum(l)-supramarginal gyrus(l), supramarginal gyrus(l)-insula(l), posterior cingulum(r)-med frontal orbital gyrus(l), thalamus(r)-cerebellum(l); MCI increased between paracentral lobule(r)-mid cingulum(r) and decreased between frontal mid orbital gyrus(r)-olfactory(r). After intervention, connectivity was greater in MCI than healthy elders in three posterior connections: mid cingulum(r)-mid temporal pole(r), superior occipital lobule(r)-cerebellum(l), and superior parietal lobule(r)-vermis. CONCLUSIONS: These findings suggest 12-weeks of walking alter functional resting state networks in MCI as well as in healthy elders. While posterior functional connections tend to be lost in AD, those with MCI in our study exhibited greater posterior functional connections than healthy elders post-intervention, which may explain how physical activity delays the onset of AD. Increased connectivity is a compensatory response to neuronal damage. Thus decreased post-intervention connectivity in healthy elders may reflect a partial reversal of age-related neuronal network degradation.