Blood Biomarkers of Alzheimer's Disease Neuropathology, Cognition, and Response to a Multidomain Lifestyle Intervention: Secondary analysis of the FINGER Randomized Controlled Dementia Risk Reduction Trial

Interventions targeting lifestyle and health behaviors support cognition in older adults at risk of dementia. It remains unclear if the cognitive benefit of such interventions is modified by Alzheimer's disease (AD)-related neuropathology, and if lifestyle interventions lead to changes in blood AD biomarkers. Here, we analyzed core AD plasma biomarkers (A{beta}, p-tau181, p-tau217, p-tau231, NFL, GFAP) in the two-year FINGER randomized controlled multidomain lifestyle trial, which demonstrated cognitive efficacy in an at-risk older general population (N=1260). We found that 85% of participants had p-tau217 below the pathological threshold at baseline (Lumipulse assay). Higher biomarker levels were associated with less favorable cognitive trajectories over two years, but their ability to predict brain amyloid accumulation on PET scans was modest (e.g., p-tau217 AUC 0.72). We found no indication that baseline biomarker levels significantly modified the cognitive benefits of the intervention. Changes in biomarkers were small over two years, with most participants (82%) remaining below the pathological p-tau217 threshold. Biomarker trajectories were similar in the intervention and control groups, suggesting that the cognitive benefits of the two-year lifestyle intervention in at-risk individuals without substantial impairment may primarily involve mechanistic pathways not captured by AD blood biomarkers. These findings provide new evidence to clarify the role of AD blood biomarkers for risk stratification and prediction of response to lifestyle interventions, which is crucial to inform future dementia precision prevention strategies. ClinicalTrials.gov ID NCT01041989.