Associations of physical activity with cerebrospinal fluid biomarkers of neurodegeneration, neuroinflammation, and Alzheimer’s disease

Abstract

AbstractBackgroundAlzheimer’s disease (AD) and related dementias are public health concerns often with long preclinical phases. Thus, intervention and prevention methods in midlife could prove efficacious. Cerebrospinal fluid (CSF) biomarkers can change early in the disease process and have been utilized for dementia diagnostics. Multiple health‐related lifestyle factors have been associated with risk for AD, yet existing research on lifestyle factors has focused on clinical outcomes such as cognitive decline, mild cognitive impairment and/or AD dementia; their associations with early changes in CSF are less understood. Our aim was to determine whether physical activity (PA), a modifiable lifestyle factor, is associated with biomarkers for neurodegeneration, glial activation, and inflammation.MethodParticipants were N = 204 cognitively unimpaired adults (aged 45–80 years) from the Wisconsin Registry for Alzheimer’s Prevention and the Wisconsin Alzheimer’s Disease Research Center, two on‐going, longitudinal studies of preclinical AD. PA was defined as the weekly metabolic equivalent (MET), calculated by scoring amount and intensity of mild, moderate, and vigorous exercises per week (range 0–79 METS). We assessed CSF biomarkers using robust exploratory prototype assays from the NeuroToolKit research platform (Roche Diagnostics International, Switzerland). Participants also completed demographic and health questionnaires (Table 1). We used linear regression models to assess associations between PA and CSF biomarkers, adjusting for age at biomarker assessment, sex, education, and chronic health conditions (diabetes, hypertension, cardiovascular disease).ResultPreliminary results showed that participants who engage in more PA had higher CSF S100B concentrations, a pro‐inflammatory calcium‐binding protein (standardized b change per MET = 0.0013, 95% confidence interval: 0.0003–0.0023; p = .01). No other PA‐biomarker associations were significant.ConclusionHigher PA was significantly associated with higher CSF concentration of S100B, a marker of (astro‐)glial activation. Future studies will need to examine whether PA is associated with higher S100B in individuals along the disease continuum of AD, and whether this is reflected in the blood. Longer follow‐ups may be needed to determine associations of PA with other biomarkers, where we had limited variation in this primarily healthy study cohort.