The effect of physical activity on CSF biomarkers of Alzheimer’s disease differs between men and women

Abstract

AbstractBackgroundIncreasing evidence suggests that sex influences several aspects of Alzheimer’s disease (AD). Cardiovascular risk factors are associated with AD, and men and women differ in the prevalence of these risk factors. We aimed at determining whether (1) sex and cardiovascular risk factors have an effect on CSF biomarkers; (2) sex modifies the association between cardiovascular risk factors and CSF biomarkers in middle aged cognitively unimpaired individuals of the ALFA+ study.MethodWe measured CSF Ab42, Ab40, p‐tau, t‐tau, neurofilament light (NfL), neurogranin, sTREM2, YKL40, GFAP, S100, IL6, sVCAM1, sICAM1, MCP1 and α‐synuclein in 381 participants of the ALFA+ study (34.4% Ab‐positive, 65.6% Ab‐negative; Ab42/40 cutoff = 0.071). Biomarker measurements were performed using MSD, Roche NeuroToolKit and Elecsys® immunoassays. The following cardiovascular risk variables were studied: hypertension, smoking, dyslipidaemia, physical activity, LDL and HDL cholesterol, glucose, Hb1Ac, triglycerides, BMI and systolic and diastolic blood pressure. ANCOVA was performed to test the effect of sex on each biomarker and potential interaction effects between sex and cardiovascular variables.ResultWe found that CSF NfL, GFAP, IL6, sVCAM1 and MCP1 were higher in men, while CSF neurogranin and YKL40 were higher in women. These differences were still significant after adjusting for Ab pathology. Regarding cardiovascular variables, men had higher diastolic blood pressure, glucose and triglycerides, while women had higher total, LDL and HDL cholesterol. After adjusting for these cardiovascular variables, sex differences in CSF NfL were still significant, suggesting that they were not confounded by cardiovascular factors (Table 1). In the whole cohort, we observed that sex modifies the association with physical activity levels and CSF NfL (interaction ‘sex x physical activity’: p=0.019). After stratifying by Ab status, we observed that higher physical activity was associated with lower CSF NfL only in Ab positive men (Figure 1).ConclusionSex affects CSF biomarkers and modifies their association with cardiovascular risk factors. Specifically, physical activity is associated with lower NfL in middle aged men in the preclinical stage of the Alzheimer’s continuum, but not in women. Our results suggest that the impact of cardiovascular risk factors on neurodegeneration differs between men and women.