The influence of midlife morbidity clusters on dementia risk: The ARIC study

Year: 2026

Type: article

Abstract: INTRODUCTION: Understanding comorbidities' combined impacts on dementia risk may offer a more comprehensive understanding of individuals' risk. Using machine-learning, we grouped individuals with similar midlife risk profiles into clusters and explored associations with dementia risk. METHODS: Participants without dementia at baseline (1987-1989) from the prospective Atherosclerosis Risk in Communities (ARIC) study were included (ages 45-64 years; N = 15,250). Using unsupervised hierarchical cluster analysis, nine clusters were created and defined based on 14 midlife morbidities. The associations with incident dementia (N = 3272 cases, median follow-up 25 years) and deaths (N = 9099) were evaluated using time-to-event regression models. RESULTS: Compared with the healthiest cluster (Cluster 1), Clusters 2 (smoking) (hazard ratio [HR](95% confidence interval [CI]) = 1.62 (1.08, 2.43)), 5 (obesity, diabetes, hypertension, and hypertriglyceridemia) (HR(95%CI) = 1.91 (1.35,2.70)), and 7/8 (atrial fibrillation/heart failure) (HR(95%CI) = 2.69 (1.59,4.57)) were associated with dementia. Accounting for competing risk of death in the Fine-Gray subdistribution model negated the cluster-dementia association. DISCUSSION: Midlife morbidity clusters are important for dementia and mortality risk.

Source: Alzheimer s & Dementia

DOI: 10.1002/alz.71110

Authors: Elise Kinyanjui, Renee C. Groechel, Valerie Morrill, Keenan A. Walker, Anna M. Kucharska‐Newton, Thomas H. Mosley, Silvia Koton, David S. Knopman, Jordan Weiss, Rebecca F. Gottesman, Marco Egle

Institutions: National Institutes of Health, National Institute of Neurological Disorders and Stroke, St. Mary's College of Maryland, National Institute on Aging, University of North Carolina at Chapel Hill, University of Mississippi Medical Center, Johns Hopkins University, Tel Aviv University, New York University, Mayo Clinic

Language: English

Topic: Dementia and Cognitive Impairment Research

Subfield: Psychiatry and Mental health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,200

Funders: National Institutes of Health, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute on Deafness and Other Communication Disorders, National Institute of Neurological Disorders and Stroke, Intramural Research Program

OpenAlex ID: W7128550256