Can vigorous physical activity mitigate the effect of systemic inflammation on cognitive performance? Results from a large older community dwelling population in The Netherlands

Background Elevated systemic inflammation is associated with poorer cognitive function, while vigorous physical activity enhances cognition. Objective This study examines whether physical activity moderates the relationship between systemic inflammation and cognitive performance. Methods We analyzed 24,661 adults (50+) from the Dutch Lifelines cohort across two waves. Cognitive performance was assessed via a validated composite score from the Cogstate Brief Battery, with higher scores indicating lower cognitive performance. Leukocyte count (3–11 × 10 9 cells/liter) served as a systemic inflammation biomarker, categorized as low (<6.5 × 10 9 cells/liter) or high (≥6.5 × 10 9 cells/liter). We used the Short Questionnaire to Assess Health-Enhancing Physical Activity to define moderate (0, 1–149, 150+ minutes) and vigorous (0, 1–74, 75+ minutes) physical activity. We performed linear regression models to examine the effect of inflammation and vigorous physical activity on cognition, adjusting for moderate physical activity and covariates. An interaction effect analyzed the potential moderation of vigorous physical activity. Results Individuals with high systemic inflammation (SI) levels in both waves exhibited significantly longer reaction times (b = 0.062 [95% confidence interval: 0.002; 0.122]) compared to those with low SI levels in both waves. Individuals who engaged in 1–74 min or 75+ minutes of vigorous physical activity had significantly faster reaction times (1–74: b = −0.114 [−0.193; −0.034], 75+: b = −0.160 [−0.210; −0.111]) than those who did not. The interaction term was insignificant. Conclusions Although vigorous physical activity is protective, it cannot mitigate the negative association between systemic inflammation and cognition. Nevertheless, promoting vigorous physical activity in an ageing population can be an effective strategy for preventing or delaying cognitive decline.