M. Cochran, J. Pugh, T. Coleman, W. Kelley, P. Jamieson, E. Dunne, P. Smith, J. Chasteen, M. Jones, J. Turner, H. Hurns, G. Geissler, M. Brunkow, S. Q. Johnston, K. Metzger, L. Seyfarth, J. Taylor, E. Shields, W. Herrington, W. Schroer, S. Newberry, A. Hurst, J. Yurkovich, N. Lamb, L. Hood, S. Evans, F. P. Behn, J. Lovejoy, J. N. Cochran
INTRODUCTION: Multimodal lifestyle interventions can delay or slow Alzheimer's disease (AD) in at-risk older adults, and plasma pTau217, a blood-based biomarker, now enables scalable AD risk stratification. Population-level screening integrating genetic, biomarker, and lifestyle risk factors, alongside attitudes toward risk disclosure, remains understudied. This pilot assessed dementia-risk attitudes before and after disclosure and tested a personalized, data-driven multimodal coaching intervention in a high-risk Alabama population. METHODS: Cognitively normal adults aged 65-75 with a first-degree relative affected by AD/dementia were recruited in north Alabama and screened using the Montreal Cognitive Assessment, family history, APOE genotyping, non-APOE AD polygenic risk score, and plasma pTau217. A composite rubric classified high-risk status (score >5 and/or pTau217 >0.18 pg/mL); high-risk participants received results disclosure and a 6-month personalized intervention (dietitian-led coaching, cognitive training, activity tracking). Pre- and post-disclosure attitudes, distress (REVEAL IGT-AD scale), and biomarker/cognitive measures were assessed. RESULTS: Of 138 screened participants, 52 (37.7%) were high-risk, most (69.2%) by pTau217 alone. Before disclosure, subjective dementia-risk perception correlated with objective risk score. Scores consistent with post-disclosure clinically significant distress occurred in 28% of survey respondents in at least one timepoint but was often (50%) observed with pre-existing anxiety/depression. Over 6 months, MoCA scores and lifestyle risk indices were unchanged, pTau217 continued rising but at a slowed rate compared to between screening and the beginning of the lifestyle intervention, and self-reported worry and perceived dementia risk decreased significantly. DISCUSSION: A genomics- and biomarker-informed screening and coaching model is feasible in a high-risk cohort in the deep south, with manageable distress and improved attitudes despite limited short-term biological change. Findings support larger, longer, and more diverse trials validating this approach for AD screening.