In a secondary analysis of the landmark FINGER randomized controlled trial (N=1,260 at-risk older adults), six core Alzheimer's disease plasma biomarkers — Aβ, p-tau181, p-tau217, p-tau231, NFL, and GFAP — were measured at baseline and tracked across two years of a multidomain lifestyle intervention (diet, exercise, cognitive training, vascular monitoring). Critically, 85% of participants had p-tau217 below the pathological threshold at baseline. Higher biomarker levels correlated with less favorable cognitive trajectories overall, yet baseline biomarker status did not significantly modify who benefited from the intervention. Biomarker levels changed minimally over two years and similarly across intervention and control groups.
This finding carries meaningful practical weight. The two-year FINGER protocol — already the most rigorously tested multidomain lifestyle program for dementia prevention — appears to confer cognitive benefit through mechanisms other than reducing amyloid or tau pathology, possibly involving vascular health, synaptic resilience, or neuroinflammatory pathways. For adults and clinicians, this suggests blood-based AD biomarker testing should not be used as a gating criterion to decide who deserves lifestyle intervention; benefit appears broadly distributed. A limitation worth noting: p-tau217's predictive accuracy for amyloid PET was modest (AUC 0.72), and most participants lacked substantial neuropathology at baseline, limiting generalizability to higher-risk populations. As a preprint not yet peer-reviewed, these results could shift with formal scrutiny. Still, the finding is incrementally important for precision prevention frameworks being built around blood biomarker screening.