Interaction Between Arteriosclerosis and Amyloid-β on Cognitive Function

J Alzheimers Dis. 2024;97(2):953-961. doi: 10.3233/JAD-230604.


Background: Dementia is a multifactorial disease, with Alzheimer's disease (AD) and vascular pathology often co-occurring in many individuals with dementia. Yet, the interplay between AD and vascular pathology in cognitive decline is largely undetermined.

Objective: The aim of the present study was to examine the joint effect of arteriosclerosis and AD pathology on cognition in the general population without dementia.

Methods: We determined the interaction between blood-based AD biomarkers and CT-defined arteriosclerosis on cognition in 2,229 dementia-free participants of the population-based Rotterdam Study (mean age: 68.9 years, 52% women) cross-sectionally.

Results: Amyloid-β (Aβ)42 and arterial calcification were associated with cognitive performance. After further adjustment for confounders in a model that combined all biomarkers, only arterial calcification remained independently associated with cognition. There was a significant interaction between arterial calcification and Aβ42 and between arterial calcification and the ratio of Aβ42/40. Yet, estimates attenuated, and interactions were no longer statistically significant after adjustment for cardio metabolic risk factors.

Conclusions: Arteriosclerosis and AD display additive interaction-effects on cognition in the general population, that are due in part to cardio metabolic risk factors. These findings suggest that joint assessment of arteriosclerosis and AD pathology is important for understanding of disease etiology in individuals with cognitive impairment.

Keywords: Alzheimer’s disease; amyloid-β; arteriosclerosis; calcification; dementia; plasma biomarkers.

MeSH terms

  • Aged
  • Alzheimer Disease* / pathology
  • Amyloid beta-Peptides / metabolism
  • Arteriosclerosis* / complications
  • Arteriosclerosis* / diagnostic imaging
  • Biomarkers
  • Cognition
  • Cognitive Dysfunction* / metabolism
  • Female
  • Humans
  • Male
  • tau Proteins


  • Amyloid beta-Peptides
  • Biomarkers
  • tau Proteins