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Psychosocial Hierarchies of Modifiable Risk for Alzheimers Disease: A Networks Analysis

Brady, J. J. R.; Bartlett, L.; Roccati, E.; Norris, K.; Vickers, J. C.; Sinclair, D.

2025-09-12 epidemiology
10.1101/2025.09.11.25335596 medRxiv
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BackgroundThirty per-cent of multidomain risk reduction trials for Alzheimers disease and related dementias (ADRD) report limited efficacy. Identifying potential cascading influences between psychosocial ADRD risk factors is a promising strategy for increasing this efficacy rate. We aimed to identify relational hierarchies among modifiable ADRD risk factors to inform temporally optimized prevention strategies. MethodsWe applied a dual network approach--regularized partial correlation network (RPCN) and a Bayesian directed acyclic graph (DAG) generated via a novel ensemble method--to cross-sectional data from 898 community-dwelling older adults enrolled in an ADRD prevention initiative. Principal findingsThe RPCN revealed clustering among mental health domains. The DAG suggested directional associations from stress, anxiety, and coping to downstream factors including depression, social support, cognitive activity, and cardiometabolic domains (physical activity, BMI, blood pressure, and MIND diet adherence). Discussion/SignificanceThis dual-network framework highlights upstream psychosocial factors statistically associated with multiple ADRD-related risks. Models suggest targeting stress and coping may offer broad, cascading, benefits for ADRD risk reduction. Outcomes assist further exploration of strategically staggered and/or needs-based individualization of future modifiable ADRD prevention initiatives.

Published in PLOS ONE (predicted rank #1) · training set

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