Modifiable cardiovascular risk and cognitive function: findings from the Maine Syracuse Longitudinal Study
Date
2019
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Publisher
University of Delaware
Abstract
Complex cognitive changes accompany aging and it will become increasingly important to understand them as the number of adults over 65 years of age increases from 617M in 2015 to 1.6B in 2050. Normative cognitive aging is characterized by subtle cognitive decline, while nonnormative cognitive aging is characterized by accelerated decline resulting in severe disability. The hallmark of nonnormative cognitive aging is dementia, a terminal syndrome that affects 47M people globally and costs >$1T per year. Cognitive decline begins up to 30 years before the emergence of clinical symptoms in the trajectory and an intervention slowing decline could prevent up to 57% of the 131M dementia cases expected by 2050. Cardiovascular disease (CVD) is strongly implicated in dementia pathophysiology and modifiable cardiovascular (CV) risk is a prime target for interventions designed to slow nonnormative cognitive aging and ultimately reduce dementia burden. However, further research characterizing associations between modifiable CV risk and cognitive function is needed before interventions can be developed and implemented. ☐ Multivariable screening tools are used to determine aggregate CV risk and guide treatment decisions in primary care settings. Aim 1 of this research was to determine whether these screening tools could also be used to identify adults early in the nonnormative cognitive aging trajectory when intervention would be most effective. We found that higher Framingham Risk Score (FRS) and Maine Syracuse Longitudinal Study Cardiovascular Risk Factor Scale (MSLS-CVRFS) score predicted lower cognitive function cross-sectionally, prospectively and longitudinally in 600 community-dwelling adults of the MSLS (MAge 62.0±11.9 years; 61% female). ☐ Modifiable CV risk factors (CV-RFs) are strictly controlled in primary care settings to prevent CVD, albeit their association with cognitive function is less clear. Aim 2 was to determine which major modifiable CV-RFs to target in interventions designed to slow cognitive decline. We found that higher systolic blood pressure (BP), diastolic BP and fasting glucose and lower high density lipoprotein cholesterol (HDL-C) were associated with lower cognitive function cross-sectionally, prospectively and longitudinally in 600 community-dwelling adults of the MSLS (MAge 62.0±11.9 years; 61% female). Associations for systolic BP, diastolic BP and fasting glucose became significant with advancing age, while those for HDL-C were observed at all ages. ☐ CVD and dementia pathophysiology involve arterial stiffening, a process driven by increased modifiable CV and genetic risk. Therapeutic strategies have been proposed to modulate stiffening processes and could be used to slow decline in susceptible adults. However, the underlying cause of decline must be addressed and the role of arterial stiffness in associations between modifiable CV risk and cognitive function is unclear. Aim 3 was to examine arterial stiffness as a mediator of associations between modifiable CV risk and cognitive function in 577 community-dwelling adults of the MSLS (MAge 66.3±11.8 years; 61% female) with variable genetic risk. We found that arterial stiffness mediated cross-sectional associations between modifiable CV risk and cognitive function in carriers, but not noncarriers of the apolipoprotein E (ApoE) ε4 allele. ☐ Our findings have the potential to inform methods for identifying and treating adults early in the nonnormative cognitive aging trajectory. Systolic BP, diastolic BP, fasting glucose, HDL-C and arterial stiffness are important intervention targets that should be treated early, especially in the context of higher aggregate CV and genetic risk. As interventions are developed, physicians are encouraged to educate patients on the importance of maintaining CV health for promoting enhanced brain aging.