Multimorbidity burden and dementia risk in older adults: The role of inflammation and genetics

Abstract

Introduction: We investigate dementia risk in older adults with different disease patterns and explore the role of inflammation and apolipoprotein E (APOE) genotype.

Methods: A total of 2,478 dementia-free participants with two or more chronic diseases (ie, multimorbidity) part of the Swedish National study on Aging and Care in Kungsholmen (SNAC-K) were grouped according to their multimorbidity patterns and followed to detect clinical dementia. The potential modifier effect of C-reactive protein (CRP) and apolipoprotein E (APOE) genotype was tested through stratified analyses.

Results: People with neuropsychiatric, cardiovascular, and sensory impairment/cancer multimorbidity had increased hazards for dementia compared to the unspecific (Hazard ration (HR) 1.66, 95% confidence interval [CI] 1.13-2.42; 1.61, 95% CI 1.17-2.29; 1.32, 95% CI 1.10-1.71, respectively). Despite the lack of statistically significant interaction, high CRP increased dementia risk within these patterns, and being APOE ε4 carriers heightened dementia risk for neuropsychiatric and cardiovascular multimorbidity.

Discussion: Individuals with neuropsychiatric, cardiovascular, and sensory impairment/cancer patterns are at increased risk for dementia and APOE ε4, and inflammation may further increase the risk. Identifying such high-risk groups might allow tailored interventions for dementia prevention.

Keywords: dementia; genetics; inflammation; multimorbidity patterns.

FIGURE 1

Incidence rates (IRs) per 100 person‐years and hazard ratios (HRs) of dementia with 95% confidence intervals (CIs) by baseline multimorbidity pattern, according to serum C‐reactive protein (CRP) levels and apolipoprotein E (APOE) genotype. HRs are plotted on a logarithmic scale. P for interaction: CRP: Neuropsychiatric MM#CRP: P = 0.151. Cardiovascular MM#CRP: P = 0.147. Sensory impairment/cancer MM#CRP: P = 0.833. Respiratory/metabolic/MSK MM#CRP: P = 0.419. APOE: Neuropsychiatric MM#APOE: P = 0.227. Cardiovascular MM#APOE: P = 0.895. Sensory impairment/cancer MM#APOE: P = 0.241. Respiratory/metabolic/MSK MM#APOE: P = 0.983. Models are adjusted for: Panel A: age, sex, education, civil status, malnutrition, and baseline Mini‐Mental State Examination score, and APOE ε4 allele. Panel B: age, sex, education, civil status, malnutrition, and baseline Mini‐Mental State Examination score, and CRP levels.