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Updated: Aug 21, 2026

Generalized Psychophysiological Interaction (PPI) Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease
Published on: November 14, 2017
Prospective study on physical activity and Alzheimer's disease-related biomarkers
Paula Iso-Markku1,2,3,4, Xin M Tu1,2, Robert A Rissman1
1Department of Psychiatry, University of California, San Diego, La Jolla, California, USA.
Introduction:
Evidence regarding the association between physical activity (PA) and Alzheimer's disease (AD)-related biomarkers is scarce and inconsistent.
Methods:
At ages 56 and 67, 564 men from the Vietnam Era Twin Study of Aging reported their PA during the preceding week from which metabolic equivalent of energy expenditure (MET) hours were determined. At age 67 we assayed plasma AD-related biomarkers (phosphorylated tau [p-tau]217, neurofilament light chain [NfL], amyloid beta (Aβ)42/40 ratio, and glial fibrillary acidic protein [GFAP]). We used generalized estimating equations to test whether PA at ages 56 or 67 was associated with these biomarkers at 67.
Results:
Age 56 MET hours were inversely associated with NfL and GFAP at 67 (NfL: B = -0.10, 95% confidence interval [CI]: -0.17 to -0.03, GFAP: B = -0.08, 95% CI: -0.15 to -0.01) but were not significantly associated with p-tau217 or Aβ42/40 ratio.
Discussion:
Our NfL and GFAP results suggest that midlife PA may reduce risk for neurodegeneration in older age via amyloid-independent mechanisms.
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