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
- 1HudsonAlpha Institute for Biotechnology
Abstract
INTRODUCTIONMultimodal lifestyle interventions can delay or slow Alzheimers 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.
METHODSCognitively 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.
RESULTSOf 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.
DISCUSSIONA 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.
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BibTeX
@misc{cochran2026clinical,
title = {{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}},
author = {M. Cochran and J. Pugh and T. Coleman and W. Kelley and P. Jamieson and E. Dunne and P. Smith and J. Chasteen and M. Jones and J. Turner and H. Hurns and G. Geissler and M. Brunkow and S. Q. Johnston and K. Metzger and L. Seyfarth and J. Taylor and E. Shields and W. Herrington and W. Schroer and S. Newberry and A. Hurst and J. Yurkovich and N. Lamb and L. Hood and S. Evans and F. P. Behn and J. Lovejoy and J. N. Cochran},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.19.26363495},
url = {https://www.medrxiv.org/content/10.64898/2026.09.19.26363495v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - 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
AU - M. Cochran
AU - J. Pugh
AU - T. Coleman
AU - W. Kelley
AU - P. Jamieson
AU - E. Dunne
AU - P. Smith
AU - J. Chasteen
AU - M. Jones
AU - J. Turner
AU - H. Hurns
AU - G. Geissler
AU - M. Brunkow
AU - S. Q. Johnston
AU - K. Metzger
AU - L. Seyfarth
AU - J. Taylor
AU - E. Shields
AU - W. Herrington
AU - W. Schroer
AU - S. Newberry
AU - A. Hurst
AU - J. Yurkovich
AU - N. Lamb
AU - L. Hood
AU - S. Evans
AU - F. P. Behn
AU - J. Lovejoy
AU - J. N. Cochran
PY - 2026
DA - 2026/09/19
PB - medRxiv
DO - 10.64898/2026.09.19.26363495
UR - https://www.medrxiv.org/content/10.64898/2026.09.19.26363495v1
AB - INTRODUCTIONMultimodal lifestyle interventions can delay or slow Alzheimers 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. METHODSCognitively 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. RESULTSOf 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. DISCUSSIONA 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.
ER -