DOI: 10.1002/alz.076099 ISSN: 1552-5260

Can physical activity moderate the relation between systemic inflammation and cognitive performance in an elderly community dwelling population?

Anne Fink, Constantin Reinke, Benjamin Aretz, Gabriele Doblhammer
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Developmental Neuroscience
  • Health Policy
  • Epidemiology



Elevated levels of systemic inflammation have been shown to be associated with poorer outcomes in cognitive performance. However, regular vigorous physical activity is associated with improved cognitive performance. This study analyzes if regular physical activity may moderate the effect of systemic inflammation on cognition.


We used the first two waves of the Dutch Lifelines cohort study (2006‐2015) of 19,985 individuals, who were 50 years or older at baseline. Cognitive performance was measured as psychomotor speed in wave 2 using the Cogstate Brief Battery, with higher scores corresponding to lower cognitive performance. As a biomarker of systemic inflammation, we used leukocyte count within the normal range of 4 to 10×109 cells per liter in EDTA blood samples at baseline. First, we performed linear regression models to examine the effect of inflammation and vigorous physical activity on cognition, adjusting for cognitive task accuracy, age, sex, education, and various comorbidities associated with cognitive impairment. Second, an interaction effect was used to analyze the potential moderation of physical activity.


After adjusting for cognitive task accuracy, age, sex, and education, higher levels in leukocyte count were significantly associated with worse cognitive outcome (b = 0.020,p = 0.036). This effect attenuated when controlling for physical activity and comorbidities (b = 0.011,p = 0.257). Vigorous physical activity was highly significantly associated with better cognitive performance (b = ‐0.126,p<0.001). Analysis of the interaction between leukocyte count and physical activity showed a borderline significant slope for physically active subjects (b = 0.029,p = 0.093) and no effect for physically inactive subjects (b = 0.003,p = 0.782). When comparing predicted psychomotor speed scores for physically active and inactive individuals, we found significantly better cognitive outcomes for active individuals with leukocyte counts between 4 and 7×109 cells per liter, while individuals with leukocyte counts between 7 and 10×109 cells per liter did not differ significantly by physical activity.


In individuals with leukocyte levels up to 7×109 cells per liter, indicating low levels of inflammation, we found a protective effect of physical activity on cognition. Because physical activity had no effect in individuals with higher leukocyte levels (albeit within the normal range), physical activity appears to have preventive rather than intervening effects on cognitive performance.

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