Memory Function and Brain Functional Connectivity Adaptations Following Multiple-Modality Exercise and Mind-Motor Training in Older Adults at Risk of Dementia: An Exploratory Sub-Study

Background Multiple-modality exercise improves brain function. However, whether task-based brain functional connectivity (FC) following exercise suggests adaptations in preferential brain regions is unclear. The objective of this study was to explore memory function and task-related FC changes following multiple-modality exercise and mind-motor training in older adults with subjective cognitive complaints. Methods We performed secondary analysis of memory function data in older adults [n = 127, mean age 67.5 (7.3) years, 71% women] randomized to an exercise intervention comprised of 45 min of multiple-modality exercise with additional 15 min of mind-motor training (M4 group, n = 63) or an active control group (M2 group, n = 64). In total, both groups exercised for 60 min/day, 3 days/week, for 24 weeks. We then conducted exploratory analyses of functional magnetic resonance imaging (fMRI) data collected from a sample of participants from the M4 group [n = 9, mean age 67.8 (8.8) years, 8 women] who completed baseline and follow-up task-based fMRI assessment. Four computer-based memory tasks from the Cambridge Brain Sciences cognitive battery (i.e. Monkey Ladder, Spatial Span, Digit Span, Paired Associates) were employed, and participants underwent 5 min of continuous fMRI data collection while completing the tasks. Behavioral data were analyzed using linear mixed models for repeated measures and paired-samples t-test. All fMRI data were analyzed using group-level independent component analysis and dual regression procedures, correcting for voxel-wise comparisons. Results Our findings indicated that the M4 group showed greater improvements in the Paired Associates tasks compared to the M2 group at 24 weeks [mean difference: 0.47, 95% confidence interval (CI): 0.08 to 0.86, p = 0.019]. For our fMRI analysis, dual regression revealed significant decrease in FC co-activation in the right precentral/postcentral gyri after the exercise program during the Spatial Span task (corrected p = 0.008), although there was no change in the behavioral task performance. Only trends for changes in FC were found for the other tasks (all corrected p < 0.09). In addition, for the Paired Associates task, there was a trend for increased co-activation in the right temporal lobe (Brodmann Area = 38, corrected p = 0.07), and left middle frontal temporal gyrus (corrected p = 0.06). Post hoc analysis exploring voxel FC within each group spatial map confirmed FC activation trends observed from dual regression. Conclusion Our findings suggest that multiple modality exercise with mind-motor training resulted in greater improvements in memory compared to an active control group. There were divergent FC adaptations including significant decreased co-activation in the precentral/postcentral gyri during the Spatial Span task. Borderline significant changes during the Paired Associates tasks in FC provided insight into the potential of our intervention to promote improvements in visuospatial memory and impart FC adaptations in brain regions relevant to Alzheimer's disease risk.