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Background: Sedentary behavior is associated with cognitive impairment, but the neuropathological mechanisms underlying their associations are poorly understood.

Objective: To investigate the associations of accelerometer-measured sedentary behavior patterns with brain structure and cognition, and further to explore the potential mechanisms.

Methods: This community-based study included 2,019 older adults (age≥60 years, 59% women) without dementia derived from participants in the baseline examination of MIND-China (2018-2020). We assessed sedentary parameters using an accelerometer and cognitive function using a neuropsychological test battery. Structural brain markers were assessed on the structural brain MRI scans in a subsample (n = 1,009). Data were analyzed using the general linear, isotemporal substitution, and mediation models.

Results: In the total sample (n = 2,019), adjusting for multiple covariates and moderate-to-vigorous-intensity physical activity, longer mean sedentary bout duration was linearly related with lower z-scores of global cognition, verbal fluency, and memory (p_trend < 0.05), whereas greater total sedentary time was linearly associated with lower z-scores of global cognition, verbal fluency, and memory only among individuals with long sedentary time (>10 h/day) (p_trend < 0.05); Breaking up sedentary time with same amount of light-intensity physical activity was significantly associated with higher verbal fluency and memory z-scores (p < 0.05). In the MRI subsample (n = 1,009), separately entering structural brain MRI markers into the mediation models substantially attenuated the associations of mean sedentary bout duration with global cognition, verbal fluency, and memory z-scores.

Conclusion: Prolonged uninterrupted sedentary time is associated with poor global cognition, memory, and verbal fluency among rural older adults, and structural brain markers could partially mediate the association.