Associations Of Objective Movement Behaviors With Systemic Low-grade Inflammation And Peripheral Alzheimer’s Disease Biomarkers: The MIND-China Study

Background and Objectives:Population-based cross-sectional studies have suggested that self-reported movement behavior is associated with biomarkers of Alzheimer’s disease(AD)and neurodegeneration in the brain and cerebrospinal fluid,while related peripheral biomarkers have been shown to be closely associated with the biomarkers in brain and cerebrospinal fluid.However,few studies explored the association between objectively-measured movement behavior and peripheral biomarkers.Furthermore,the potential mechanisms underlying these associations have not been elucidated.Previous studies support that systemic low-grade inflammation is involved in the pathogenesis of neurodegeneration and AD,while it is currently accepted that an unhealthy lifestyle,such as sedentary lifestyle,fosters a state of low-grade inflammation.In this study,we explored the dose-response associations of objectively-measured sedentary behavior(SB)and physical activity(PA),including light-intensity PA(LPA)and moderate-to-vigorous-intensity PA(MVPA),with plasma AD-related biomarkers(amyloid beta protein[Aβ],Total tau[T-tau],and Neurofilament light chain[NfL])and relationship of movement behavior with systemic low-grade inflammation,and further examined the role of systemic low-grade inflammation playing in the association of movement behavior with AD-related biomarkers.Methods:This cross-sectional study derived from the baseline data in 2018 of the MIND-China study,and demographic data and history of diseases were collected through face-to-face interviews.ActiGraph,a triaxial accelerometer,was used to collect movement behavior data.Plasma Aβ,T-tau,NfL,and serum cytokines were detected through immunoassay technique.Dementia was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition criteria.We included 1,029 dementia-free older adults aged≥60 years(59.48%female)in this study.Multiple linear regression models and restricted cubic splines models were used to examine the relationship between movement behavior and plasma AD-related biomarkers and serum cytokines,and mediation models were further used to explore the mediating role of systemic low-grade inflammation playing in the associations.Results:1.After adjusting for demographic characteristics,APOE ε4 carrier,lifestyle,chronic medical history,ActiGraph wearing season and wearing time,and other movement behaviors,no significant associations were found between remained kinds of movement behaviors and plasma Aβ,except for a J-shaped correlation between LPA and plasma Aβ.SB and LPA,rather than MVPA,were linearly associated with T-tau in positive and negative dose-response pattern.And all movement behaviors showed J-shaped dose-response relationships with plasma NfL,namely:only when SB≥8.00 hours/day,LPA<5.00 hours/day,MVPA<2.00 hours/day,longer daily SB time(β=0.049[0.005,0.093]),shorter daily LPA(β=-0.073[-0.123,-0.023])or MVPA(β=-0.018[-0.175,-0.041])time were associated with lower plasma NfL.The adverse effect of SB on NfL can be overcame by PA when LPA≥6.01 hours/day or MVPA≥0.31 hours/day.2.In fully-adjusted models,longer daily SB time(β=0.04[0.02,0.07])as well as shorter daily LPA(β=-0.05[-0.09,-0.02])or MVPA(β=-0.07[-0.12,-0.01])time were significantly associated with higher systemic low-grade inflammation composite score.However,the relationship between MVPA and low-grade inflammation disappeared after further adjustment for LPA.3.Mediating analysis was examined after adjusting for demographic and ActiGraph-related parameters,which showed that low-grade inflammation completely mediated the relationship of SB and T-tau and partially mediated the associations of LPA with T-tau as well as movement behavior with NfL,ranging from 14%to 23%.Conclusion:Reduced sedentary time and increased physical activity were beneficial to delay neurodegeneration and decrease systemic low-grade inflammation level in rural-dwelling dementia-free older adults.The relationships between movement behavior and biomarkers of neurodegeneration may be mediated in part or completely by systemic low-grade inflammation.