Physical activity across the life course and neural biomarkers.

Young adult occupation/school physical activity was a significant predictor of neurofilament light protein (NfL) levels.

• Odds ratio for young adult occupation/school PA predicting NfL was OR = 0.969 (95% CI = 0.940–0.999), indicating a protective association.
• The full logistic regression model was significant: χ²(df = 2) = 15.57, p < 0.001.
• The model explained 19.2–25.6% of the variance in NfL.
• NfL is a biomarker of neurodegeneration measured via cerebrospinal fluid using the Roche NeuroToolKit panel.

Young adult occupation/school physical activity was a significant predictor of alpha-synuclein levels.

• Odds ratio for young adult occupation/school PA predicting alpha-synuclein was OR = 0.968 (95% CI = 0.940–0.996).
• The full logistic regression model was significant: χ²(df = 1) = 6.70, p = 0.01.
• The model explained 8.8–11.7% of the variance in alpha-synuclein.
• Alpha-synuclein was measured via cerebrospinal fluid using the Roche NeuroToolKit exploratory prototype assays.

The study assessed multiple types of physical activity (occupation/school, transportation, household) across multiple life course stages (school-age, adolescence, young adult, middle adult).

• Physical activity types included occupation/school, transportation, and household activity.
• Life course periods examined were school-age, adolescence, young adulthood, and middle adulthood.
• Significant bivariate correlations were followed by logistic regression as the analytic approach.
• Biomarkers measured included AD pathology, neurodegeneration, synaptic dysfunction, and gliosis beyond the AT(N) framework.

Cerebrospinal fluid biomarkers beyond the AT(N) framework were measured using the Roche NeuroToolKit panel of exploratory prototype assays.

• The Roche NeuroToolKit is described as 'a panel of exploratory prototype assays for cerebrospinal fluid biomarkers.'
• Biomarkers encompassed AD pathology, neurodegeneration, synaptic dysfunction, and gliosis.
• NfL and alpha-synuclein were among the biomarkers assessed in this panel.
• The study aimed to examine biomarkers beyond the standard amyloid-β (A), tau (T), and neurodegeneration (N) framework.

ADRD prevention may be most effective when administered earlier in the life course, as brain changes may occur 20–25 years before symptom onset.

• The authors note that 'ADRD prevention may be most effective when administered earlier in the life course.'
• Brain changes in AD are stated to occur '20-25 years before the onset of symptoms.'
• Most prior research has focused on exercise rather than broader types of physical activity.
• The association between different types of PA across the life course and biomarkers beyond AT(N) was previously unknown.