Physical activity across the life course and neural biomarkers

BackgroundPhysical activity (PA) may decrease the risk of Alzheimer's disease and related disorders (ADRD), although most research has focused on exercise. In addition, ADRD prevention may be most effective when administered earlier in the life course, when changes in the brain may occur 20-25 years before the onset of symptoms. Finally, amyloid-β (A) and tau (T) accumulation are followed by neurodegeneration (N), key features of AD. However, there are additional biomarkers associated with ADRD. The association between different types of PA across the life course and biomarkers beyond the AT(N) framework is unknown.ObjectiveExamine the association between different types of PA across the life course and biomarkers beyond the AT(N) framework.MethodsPA (occupation/school, transportation, household) across the life course (school-age, adolescence, young adult, middle adult) was assessed. AD pathology, neurodegeneration, synaptic dysfunction, and gliosis were measured with the Roche NeuroToolKit, a panel of exploratory prototype assays for cerebrospinal fluid biomarkers. Significant bivariate correlations were followed by logistic regression.ResultsYoung adult occupation/school PA was a significant predictor of neurofilament light protein (NfL, OR = 0.969, 95% CI = 0.940-0.999); the full model was significant, χ²(df = 2) = 15.57, <i>p</i> < 0.001, explaining 19.2-25.6% of the variance in NfL. Young adult occupation/school PA was a significant predictor of alpha-synuclein (OR = 0.968, 95% CI = 0.940-0.996); the full model was significant, χ²(df = 1) = 6.70, <i>p</i> <i>=</i> 0.01, explaining 8.8-11.7% of the variance in alpha-synuclein.ConclusionsPA done as part of one's job or schooling during young adulthood, such as standing and walking, may be protective against dementia later in life.