Clinical and attitudinal outcomes of a personalized, multimodal lifestyle intervention for Alzheimer’s disease prevention in high-risk, cognitively normal older adults in north Alabama: A pilot study
Year: 2026
Type: preprint
Study design: Clinical Trial
Abstract: 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. Populationlevel 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 postdisclosure 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.
Source: medRxiv
Authors: Meagan Cochran, Jada Pugh, Tanner Coleman, Whitley Kelley, Paige Jamieson, Elizabeth Dunne, Patti Smith, Jessica Chasteen, Mary Jones, Jenny Turner, Halle Burns, Gwendolyn Geissler, Mary Brunkow, S. Quinn Johnston, Katherine Metzger, Lena Seyfarth, Jared Taylor, Emily Shields, William Herrington, Wayne Schroer, Scott Newberry, Anna C.E. Hurst, James Yurkovich, Neil Lamb, Lee Hood, Simon Evans, Florencia P. Behn, Jennifer Lovejoy, J. Nicholas Cochran
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7213899639