Multimorbidity, cognitive phenotypes, and Alzheimer's disease plasma biomarkers in older adults: A population‐based study

Abstract INTRODUCTION To examine the burden and clusters of multimorbidity in association with mild cognitive impairment (MCI), dementia, and Alzheimer's disease (AD)‐related plasma biomarkers among older adults. METHODS This population‐based study included 5432 participants (age ≥60 years); of these, plasma amyloid beta (Aβ), total tau, and neurofilament light chain (NfL) were measured in a subsample ( n = 1412). We used hierarchical clustering to generate five multimorbidity clusters from 23 chronic diseases. We diagnosed dementia and MCI following international criteria. Data were analyzed using logistic and linear regression models. RESULTS The number of chronic diseases was associated with dementia (multivariable‐adjusted odds ratio = 1.22; 95% confidence interval [CI] = 1.11 to 1.33), AD (1.13; 1.01 to 1.26), vascular dementia (VaD) (1.44; 1.25 to 1.64), and non‐amnestic MCI (1.25; 1.13 to 1.37). Metabolic cluster was associated with VaD and non‐amnestic MCI, whereas degenerative ocular cluster was associated with AD ( p < 0.05). The number of chronic diseases was associated with increased plasma Aβ and NfL ( p < 0.05). DISCUSSION Multimorbidity burden and clusters are differentially associated with subtypes of dementia and MCI and AD‐related plasma biomarkers in older adults. Highlights We used hierarchical clustering to generate five clusters of multimorbidity. The presence and load of multimorbidity were associated with dementia and mild cognitive impairment. Multimorbidity clusters were differentially associated with subtypes of dementia and Alzheimer's disease plasma biomarkers.