Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024;97(2):953-961.
doi: 10.3233/JAD-230604.

Interaction Between Arteriosclerosis and Amyloid-β on Cognitive Function

Ingeborg Frentz  1   2 , Joyce van Arendonk  1   3 , Anna E Leeuwis  4 , Meike W Vernooij  1   3 , Wiesje M van der Flier  4   5 , Daniel Bos  1   3 , Peter Paul De Deyn  2   6 , Frank J Wolters  1   3 , M Arfan Ikram  1
Affiliations

Interaction Between Arteriosclerosis and Amyloid-β on Cognitive Function

Ingeborg Frentz et al. J Alzheimers Dis. 2024.

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

M. Arfan Ikram is an Editorial Board Member of this journal but was not involved in the peer-review process nor had access to any information regarding its peer-review.

All other authors have no conflict of interest to report.

Figures

Fig. 1
Fig. 1
Co-occurrence of arteriosclerosis and amyloid pathology. The figure depicts the number of participants with neither pathology, arteriosclerosis only, amyloid pathology only or co-occurrence of both pathologies, stratified by age groups. Presence of arteriosclerosis was defined as the highest quartile of the C-factor, whereas presence of amyloid was defined as the lowest quartile of the Aβ42/40 ratio.
Fig. 2
Fig. 2
Association of systemic calcification with global cognition, stratified by tertile of plasma levels of Aβ40, Aβ42, and the Aβ42/40 ratio. The figure depicts the association of systemic arterial calcification level (C-factor) and the cognition outcome (g-factor) per tertile of plasma Aβ40, Aβ42, and the Aβ42/40 ratio.
See this image and copyright information in PMC

References

    1. Attems J, Jellinger KA (2014) The overlap between vascular disease and Alzheimer’s disease - lessons from pathology.. BMC Med 12, 206. - PMC - PubMed
    1. Boyle PA, Yu L, Wilson RS, Leurgans SE, Schneider JA, Bennett DA (2018) Person-specific contribution of neuropathologies to cognitive loss in old age. Ann Neurol 83, 74–83. - PMC - PubMed
    1. Musiek ES, Holtzman DM (2015) Three dimensions of the amyloid hypothesis: Time, space and “wingmen.” . Nat Neurosci 18, 800–806. - PMC - PubMed
    1. Mormino EC, Betensky RA, Hedden T, Schultz AP, Amariglio RE, Rentz DM, Johnson KA, Sperling RA (2014) Synergistic effect of β-amyloid and neurodegeneration on cognitive decline in clinically normal individuals. JAMA Neurol 71, 1379–1385. - PMC - PubMed
    1. Rabin JS, Yang HS, Schultz AP, Hanseeuw BJ, Hedden T, Viswanathan A, Gatchel JR, Marshall GA, Kilpatrick E, Klein H, Rao V, Buckley RF, Yau WYW, Kirn DR, Rentz DM, Johnson KA, Sperling RA, Chhatwal JP (2019) Vascular risk and β-amyloid are synergistically associated with cortical tau. Ann Neurol 85, 272–279. - PMC - PubMed

Publication types