Preservation of Dorsolateral Prefrontal Cortex Volume Mitigates Cognitive Decline in Community-Dwelling Older Adults: A Longitudinal Study

Introduction: Habitual physical activity is widely recognized as a neuroprotective strategy against age-related cognitive and structural decline. However, the specific longitudinal effects of real-world community-based physical activity, quantified by step counts and structured exercise participation, on concurrent brain atrophy and functional integrity remain poorly understood. Specifically, the structural integrity of the dorsolateral prefrontal cortex (DLPFC), a hub for executive function, is a key moderator of cognitive aging. The purpose of this 7-year longitudinal study was to investigate the relationship between physical activity and annual change rates in brain volume and cognitive function in community-dwelling older adults. We hypothesized that higher adherence to the exercise program and greater daily step counts would be associated with preserved brain volume and mitigated cognitive decline. Methods: This study utilized a longitudinal design across four assessments (2015, 2017, 2018, and 2022). Of the 58 participants initially enrolled, data from 34 cognitively intact older adults who completed at least two concurrent measures of both brain magnetic resonance imaging (MRI) and cognitive assessments were included in the final analysis. Structural MRI data were acquired using a 3T scanner (T1-weighted images), and the annual volume change rate (%/year) was calculated for cortical and subcortical regions. The DLPFC volume change rate was specifically calculated for primary analysis. Cognitive function was assessed using the Trail Making Test (TMT Parts A and B, providing TMT B/A ratio for executive function) and Logical Memory (episodic memory). Exposure variables included weekly exercise program participation rates and daily step counts. We used a regression model to determine annual volume change rates and Spearman’s partial correlation, controlling for age, sex, intervention years, education, and existing medical conditions, to analyze associations between physical activity metrics and functional change rates (%/year). Results: Analysis of variance revealed significant regional differences in annual volume change rate (F = 3.80, p = 0.005). The pronounced reduction rates were observed in the temporal and occipital cortices, putamen, hippocampus, amygdala, and nucleus accumbens. Interestingly, neither daily step counts nor exercise program participation rates were significantly associated with overall annual brain volume change rates. However, higher step counts were significantly associated with better episodic memory performance (rho = -0.404, p = 0.037). Critically, a greater annual volume reduction in the DLPFC was strongly associated with impaired cognitive function, as indicated by a worsening TMT B/A ratio (rho = -0.634, p < 0.001). Conclusion: This study characterizes regional brain volume reduction in older adults participating in a long-term community-based physical activity program, confirming that subcortical and posterior cortical regions exhibit significant atrophy. The strong, specific association between DLPFC volume maintenance and cognitive function integrity highlights that preserving the structural integrity of the dorsolateral prefrontal cortex is crucial for mitigating age-related cognitive decline, independent of overall physical activity levels. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.