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

Alzheimers Dement. 2021 May;17(5):768-776. doi: 10.1002/alz.12237. Epub 2021 Jan 6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Apolipoprotein E4 / genetics
  • C-Reactive Protein / analysis
  • Cohort Studies
  • Dementia / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Genotype*
  • Humans
  • Inflammation*
  • Male
  • Multimorbidity*
  • Risk Factors
  • Sweden


  • Apolipoprotein E4
  • C-Reactive Protein