Original Investigation
Associations Between Cardiovascular Risk, Structural Brain Changes, and Cognitive Decline

https://doi.org/10.1016/j.jacc.2020.03.053Get rights and content
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Abstract

Background

The impact of cardiovascular risk burden on cognitive trajectories and brain structure changes remains unclear.

Objectives

This study aimed to examine whether cardiovascular risk burden assessed by the Framingham General Cardiovascular Risk Score (FGCRS) is associated with cognitive decline and structural brain differences.

Methods

Within the Rush Memory and Aging Project, 1,588 dementia-free participants (mean age: 79.5 years) were followed for up to 21 years. FGCRS was assessed at baseline and categorized into tertiles (lowest, middle, and highest). Episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed were assessed annually with a battery of 19 tests, from which composite scores were derived. A subsample (n = 378) of participants underwent magnetic resonance imaging. Structural total and regional brain volumes were estimated. Data were analyzed using linear mixed-effects models and linear regression models.

Results

In all participants, FGCRS ranged from 4 to 28 (mean score: 15.6 ± 3.7). Compared with the lowest tertile of FGCRS, the highest tertile was associated with faster decline in global cognition (β = −0.019; 95% confidence interval [CI]: −0.035 to −0.003), episodic memory (β = −0.023; 95% CI: −0.041 to −0.004), working memory (β = −0.021; 95% CI: −0.035 to −0.007), and perceptual speed (β = −0.027; 95% CI: −0.042 to −0.011) over the follow-up. In magnetic resonance imaging data analyses, higher FGCRS was related to smaller volumes of the hippocampus (β = −0.021; 95% CI: −0.042 to −0.000), gray matter (β = −1.569; 95% CI: −2.757 to −0.382), and total brain (β = −1.588; 95% CI: −2.832 to −0.344), and greater volume of white matter hyperintensities (β = 0.035; 95% CI: 0.001 to 0.069).

Conclusions

Higher cardiovascular risk burden may predict decline in episodic memory, working memory, and perceptual speed and is associated with neurodegeneration and vascular lesions in the brain.

Key Words

cognitive decline
cohort study
Framingham General Cardiovascular Risk Score
magnetic resonance imaging
neurodegeneration
vascular lesions

Abbreviations and Acronyms

APOE
apolipoprotein E
BMI
body mass index
CI
confidence interval
CVD
cardiovascular disease
FGCRS
Framingham General Cardiovascular Risk Score
HDL
high-density lipoprotein
MAP
Rush Memory and Aging Project
MCI
mild cognitive impairment
MRI
magnetic resonance imaging
WMH
white matter hyperintensities

Cited by (0)

This project is part of CoSTREAM and received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement no. 667375. The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Dr. Bennett has received grants from the National Institutes of Health (R01AG17917 and UH2NS100599). Dr. Xu has received grants from the Swedish Research Council (no. 2017-00981), the National Natural Science Foundation of China (no. 81771519), Demensfonden, the Konung Gustaf V:s och Drottning Victorias Frimurare Foundation (no. 2016-2017), and Alzheimerfonden (2017-2019). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC author instructions page.

Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.

∗

Drs. Bennett and Xu contributed equally to this work.

© 2020 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.