Association of Cardiovascular Risk Trajectory With Cognitive Decline and Incident Dementia

Abstract

Background and objectives: Cardiovascular risk factors have a recently established association with cognitive decline and dementia, yet most studies examine this association through cross-sectional data, precluding an understanding of the longitudinal dynamics of such risk. The current study aims to explore how the ongoing trajectory of cardiovascular risk affects subsequent dementia and memory decline risk. We hypothesize that an accelerated, long-term accumulation of cardiovascular risk, as determined by the Framingham Risk Score (FRS), will be more detrimental to cognitive and dementia state outcomes than a stable cardiovascular risk.

Methods: We assessed an initially healthy, community-dwelling sample recruited from the prospective cohort Betula study. Cardiovascular disease risk, as assessed by the FRS, episodic memory performance, and dementia status were measured at each 5-year time point (T) across 20 to 25 years. Analysis was performed with bayesian additive regression tree, a semiparametric machine-learning method, applied herein as a multistate survival analysis method.

Results: Of the 1,244 participants, cardiovascular risk increased moderately over time in 60% of sample, with observations of an accelerated increase in 18% of individuals and minimal change in 22% of individuals. An accelerated, as opposed to a stable, cardiovascular risk trajectory predicted an increased risk of developing Alzheimer disease dementia (average risk ratio [RR] 3.3-5.7, 95% CI 2.6-17.5 at T2, 1.9-6.7 at T5) or vascular dementia (average RR 3.3-4.1, 95% CI 1.1-16.6 at T2, 1.5-7.6 at T5) and was associated with an increased risk of memory decline (average RR 1.4-1.2, 95% CI 1-1.9 at T2, 1-1.5 at T5). A stable cardiovascular risk trajectory appeared to partially mitigate Alzheimer disease dementia risk for APOE ε4 carriers.

Discussion: The findings of the current study show that the longitudinal, cumulative trajectory of cardiovascular risk is predictive of dementia risk and associated with the emergence of memory decline. As a result, clinical practice may benefit from directing interventions at individuals with accelerating cardiovascular risk.

Figure 1. Overview of Sample Size Over Test Sessions and Number of Participants Characterized as Having Accelerated, Average, or Stable FRS Trajectories

FRS = Framingham Risk Score.

Figure 2. CVD Risk (Percent Within a 10-Year Period) at Each 5-Year Assessment Over 25 Years for Groups With Accelerated, Average, and Stable CVD Risk Trajectories

Shaded areas represent 95% credible intervals. CVD = cardiovascular disease.

Figure 3. AD and VaD Incidence Across 25 Years in Older Individuals With Differing CVD Risk Trajectories

Higher incidence of Alzheimer disease (AD) (A) and vascular dementia (VaD) (B) across 25 years in older individuals (≥70 years of age at study inclusion) with accelerated (n = 57) compared to stable (n = 92) and average (n = 94) cardiovascular disease risk trajectories. Shaded areas represent 95% credible intervals.

Figure 4. AD Incidence for APOE e4− and APOE e4+ Participants With Differing CVD Risk Trajectories

Incidence of Alzheimer disease (AD) is elevated in (A) APOE ε4− (accelerated n = 39, average n = 62, stable n = 74) and (B) APOE ε4+ participants (accelerated n = 18, average n = 32, stable n = 18) and highest in individuals with accelerated cardiovascular disease risk trajectories. Shaded areas represent 95% credible intervals.

Figure 5. Higher Incidence of EM Decline Events Across 25 Years in Younger Individuals (Aged 35–65 at Study Inclusion) With Accelerated Compared to Stable CVD Risk Trajectories

Accelerated n = 163, average n = 656, stable n = 182. Shaded areas represent 95% credible intervals. CVD = cardiovascular disease; EM = episodic memory.