The influence of midlife morbidity clusters on dementia risk: The ARIC study.
| Title: | The influence of midlife morbidity clusters on dementia risk: The ARIC study. |
|---|---|
| Authors: | Kinyanjui E; Department of Neuroscience, St. Mary's College of Maryland, St. Mary's City, Maryland, USA.; National Institute of Neurological Disorders and Stroke, Intramural Research Program, National Institutes of Health, Bethesda, Maryland, USA.; Groechel RC; National Institute of Neurological Disorders and Stroke, Intramural Research Program, National Institutes of Health, Bethesda, Maryland, USA.; Morrill V; National Institute of Neurological Disorders and Stroke, Intramural Research Program, National Institutes of Health, Bethesda, Maryland, USA.; Walker KA; Laboratory of Behavioral Neuroscience, National Institute on Aging, Intramural Research Program, Baltimore, Maryland, USA.; Kucharska-Newton AM; Department of Epidemiology, University of North Carolina at Chapel Hill Gillings School of Global Public Health, Chapel Hill, North Carolina, USA.; Mosley TH; Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA.; Koton S; Department of Nursing, The Stanley Steyer School of Health Professions, Tel Aviv University, Tel Aviv, Israel.; Department of Epidemiology, Johns Hopkins University School of Public Health, Baltimore, Maryland, USA.; Optimal Aging Institute and Department of Medicine, New York University Grossman School of Medicine, New York, New York, USA.; Knopman DS; Department of Neurology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA.; Weiss J; Optimal Aging Institute and Department of Medicine, New York University Grossman School of Medicine, New York, New York, USA.; Gottesman RF; National Institute of Neurological Disorders and Stroke, Intramural Research Program, National Institutes of Health, Bethesda, Maryland, USA.; Egle M; National Institute of Neurological Disorders and Stroke, Intramural Research Program, National Institutes of Health, Bethesda, Maryland, USA. |
| Source: | Alzheimer's & dementia : the journal of the Alzheimer's Association [Alzheimers Dement] 2026 Feb; Vol. 22 (2), pp. e71110. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: John Wiley & Sons, Ltd Country of Publication: United States NLM ID: 101231978 Publication Model: Print Cited Medium: Internet ISSN: 1552-5279 (Electronic) Linking ISSN: 15525260 NLM ISO Abbreviation: Alzheimers Dement Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2020- : Hoboken, NJ : John Wiley & Sons, Ltd.; Original Publication: Orlando, FL : Elsevier, Inc. |
| MeSH Terms: | Dementia*/epidemiology ; Dementia*/mortality; Hypertension/epidemiology ; Obesity/epidemiology ; Humans ; Female ; Middle Aged ; Male ; Risk Factors ; Cluster Analysis ; Comorbidity ; Prospective Studies ; Clustering Algorithms ; Morbidity |
| 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.; (© 2026 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.) |
| References: | Gottesman RF, Albert MS, Alonso A, et al. Associations between midlife vascular risk factors and 25‐year incident dementia in the Atherosclerosis Risk in Communities (ARIC) cohort. JAMA Neurol. 2017;74(10):1246‐1254.; Xu W, Qiu C, Gatz M, Pedersen NL, Johansson B, Fratiglioni L. Mid‐ and late‐life diabetes in relation to the risk of dementia: a population‐based twin study. Diabetes. 2009;58(1):71‐77.; Walker KA, Sharrett AR, Wu A, et al. Association of midlife to late‐life blood pressure patterns with incident dementia. JAMA. 2019;322(6):535‐545.; Vetrano DL, Roso‐Llorach A, Fernández S, et al. Twelve‐year clinical trajectories of multimorbidity in a population of older adults. Nat Commun. 2020;11(1):3223.; Emerging Risk Factors Collaboration, Di Angelantonio E, Kaptoge S, et al, Association of cardiometabolic multimorbidity with mortality. JAMA. 2015;314(1):52‐60.; Egle M, Groechel RC, Johansen MC, Kucharska‐Newton AM, Gottesman RF, Koton S. Role of morbidity clusters in midlife on ischemic stroke incidence and severity: the ARIC study. Stroke. 2025;56(10):2930–2941.(STROKEAHA.124.049496). https://doi.org/10.1161/STROKEAHA.124.049496.; Wright JD, Folsom AR, Coresh J, et al. The ARIC (Atherosclerosis Risk In Communities) study: JACC focus seminar 3/8. J Am Coll Cardiol. 2021;77(23):2939‐2959.; Knopman DS, Gottesman RF, Sharrett AR, et al. Mild cognitive impairment and dementia prevalence: the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC‐NCS). Alzheimer Dement. 2016;2(1):1‐11.; Lê S, Josse J, F. FactoMine R: An R package for multivariate analysis. J Stat Softw. 2008;25(1):1‐18.; van Buuren S, Groothuis‐Oudshoorn K. mice: Multivariate imputation by chained equations in R. J Stat Softw. 2011;45(3):1‐67.; Loehr LR, Rosamond WD, Chang PP, Folsom AR, Chambless LE. Heart failure incidence and survival (from the Atherosclerosis Risk in Communities study). Am J Cardiol. 2008;101(7):1016‐1022.; Alonso A, Agarwal SK, Soliman EZ, et al. Incidence of atrial fibrillation in whites and African‐Americans: the Atherosclerosis Risk in Communities (ARIC) study. Am Heart J. 2009;158(1):111‐117.; Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604‐612.; Rebholz CM, Anderson CAM, Grams ME, et al. Relationship of the American heart association's Impact Goals (Life's simple 7) with risk of chronic kidney disease: results from the Atherosclerosis Risk in Communities (ARIC) cohort study. J Am Heart Assoc. 2016;5(4):e003192.; Bogle BM, Sotoodehnia N, Kucharska‐Newton AM, Rosamond WD. Vital exhaustion and sudden cardiac death in the Atherosclerosis Risk in Communities Study. Heart. 2018;104(5):423‐429.; Azur MJ, Stuart EA, Frangakis C, Leaf PJ. Multiple imputation by chained equations: what is it and how does it work?: multiple imputation by chained equations. Int J Methods Psychiatr Res. 2011;20(1):40‐49.; Austin PC, Lee DS, Fine JP. Introduction to the analysis of survival data in the presence of competing risks. Circulation. 2016;133(6):601‐609.; Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94(446):496‐509.; Jack CR Jr, Therneau TM, Lundt ES, et al. Long‐term associations between amyloid positron emission tomography, sex, apolipoprotein E and incident dementia and mortality among individuals without dementia: hazard ratios and absolute risk. Brain Commun. 2022;4(2):fcac017.; McGrath ER, Beiser AS, O'Donnell A, et al. Determining vascular risk factors for dementia and dementia risk prediction across mid‐ to later life: the Framingham heart study: the Framingham heart study. Neurology. 2022;99(2):e142‐e153.; Prados‐Torres A, Calderón‐Larrañaga A, Hancco‐Saavedra J, Poblador‐Plou B, van den Akker M. Multimorbidity patterns: a systematic review. J Clin Epidemiol. 2014;67(3):254‐266.; Egle M, Wang WC, Fann YC, et al. Sex differences in the role of multimorbidity on poststroke disability: the Taiwan Stroke Registry: the Taiwan stroke registry. Neurology. 2024;102(5):e209140.; Patel R, Gillis G, Mackay CE, et al. The lifetime accumulation of multimorbidity and its influence on dementia risk: a UK Biobank study. Brain Commun. 2025;7(4):fcaf222.; Knopman DS, Amieva H, Petersen RC, et al. Alzheimer disease. Nat Rev Dis Primers. 2021;7(1):33.; Testai FD, Gorelick PB, Chuang PY, et al. Cardiac contributions to brain health: a scientific statement from the American heart association. Stroke. 2024;55(12):e425‐e438.; Wolters FJ, Segufa RA, Darweesh SKL, et al. Coronary heart disease, heart failure, and the risk of dementia: a systematic review and meta‐analysis. Alzheimer Dement. 2018;14(11):1493‐1504.; Jefferson AL, Beiser AS, Himali JJ, et al. Low cardiac index is associated with incident dementia and Alzheimer disease: the Framingham Heart Study: the Framingham heart study. Circulation. 2015;131(15):1333‐1339.; Rajmohan R, Al‐Darsani Z, Ho CC, et al. Vascular risk factors and cerebrovascular pathologic changes on autopsy: the 90+ study. Alzheimer Dement. 2025;21(2):e14454.; Torre M, Zanella CA, Feany MB. The biological intersection between chemotherapy‐related cognitive impairment and Alzheimer disease. Am J Pathol. 2025,195(11):2088–2101.doi:10.1016/j.ajpath.2024.12.013. Published online January 23, 2025.; Gardner AW, Montgomery PS, Wang M, et al. Cognitive decrement in older adults with symptomatic peripheral artery disease. GeroScience. 2021;43(5):2455‐2465. |
| Grant Information: | U01HL096812 United States DC NIDCD NIH HHS; U01HL096814 United States DC NIDCD NIH HHS; 75N92022D00002 United States HL NHLBI NIH HHS; U01 HL096917 United States HL NHLBI NIH HHS; U01HL096902 United States DC NIDCD NIH HHS; 75N92022D00005 United States DC NIDCD NIH HHS; 75N92022D00001 United States DC NIDCD NIH HHS; United States NS NINDS NIH HHS; U01 HL096814 United States HL NHLBI NIH HHS; 75N92022D00003 United States HL NHLBI NIH HHS; 75N92022D00005 United States HL NHLBI NIH HHS; U01 HL096899 United States HL NHLBI NIH HHS; 75N92022D00001 United States HL NHLBI NIH HHS; U01 HL096812 United States HL NHLBI NIH HHS; United States AG NIA NIH HHS; U01 HL096902 United States HL NHLBI NIH HHS; 75N92022D00002 United States DC NIDCD NIH HHS; NINDS Intramural Research Program; U01HL096917 United States DC NIDCD NIH HHS; 75N92022D00004 United States HL NHLBI NIH HHS; 75N92022D00003 United States DC NIDCD NIH HHS; U01HL096899 United States DC NIDCD NIH HHS; NIA Intramural Research Program; 75N92022D00004 United States DC NIDCD NIH HHS; Intramural Research Program |
| Contributed Indexing: | Keywords: Dementia; mortality; stroke; vascular risk factors |
| Entry Date(s): | Date Created: 20260209 Date Completed: 20260610 Latest Revision: 20260627 |
| Update Code: | 20260627 |
| PubMed Central ID: | PMC12885933 |
| DOI: | 10.1002/alz.71110 |
| PMID: | 41663335 |
| Database: | MEDLINE |
Journal Article