Abstract
Background
Higher levels of physical activity (PA) have been linked to a reduced risk of Alzheimer's disease (AD) dementia among older adults. However, the mechanisms underlying the association between increased PA and a lower risk of AD‐related cognitive decline remain unclear. This study aimed to investigate the relationship between late‐life PA (PAlate) and functional connectivity (FC) within major functional resting state brain networks in cognitively healthy older adults.
Method
This study was part of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE). It included 157 cognitively normal (CN) participants who underwent comprehensive clinical assessments at baseline. The participants also received multimodal brain imaging including resting‐state functional MRI, structural MRI, [11C] Pittsburgh Compound B (PiB) positron emission tomography (PET), [18F] fluorodeoxyglucose (FDG) PET, as well as an evaluation for PAlate. For major functional resting state networks (RSN) including the frontotemporal, default mode, dorsal attention, limbic, and salience (ventral attention) networks, within‐system FC was calculated as the median value of Fisher z‐transformed node‐to‐node functional connectivity within each network.
Result
PAlate demonstrated a significant positive association with FC of the default mode network (beta = 0.216, p = 0.010). No significant associations were found in other networks. The association between PAlate and the default mode network FC remained significant even after controlling for AD imaging biomarkers, including global amyloid retention, AD signature region cerebral glucose metabolism, and AD signature region cortical thickness.
Conclusion
These findings indicate that PAlate is associated with increased functional connectivity within the default mode network, independent of AD‐related brain pathologies. While further research is needed, these findings suggest a potential role in reducing the risk of AD and related cognitive decline.



