Association Between Behavioral, Biological, and Genetic Markers of Cardiovascular Health and MRI Markers of Brain Aging

Abstract

Background and Objective:The Life’s Simple 7 approach was proposed to define cardiovascular health (CVH) metrics. We sought to investigate the associations between behavioral, biological, and genetic markers for CVH and vascular brain aging in older adults.Methods:This population-based cohort study included participants who had repeated brain MRI measures from 2001-2003 to 2007-2010 (i.e., count of perivascular spaces, volumes of white-matter hyperintensity [WMH] and grey matter, and lacunes). At baseline, global, behavioral, and biological CVH metrics were defined and scored following the Life’s Simple 7 approach and categorized into unfavorable, intermediate, and favorable profiles according to tertiles. The metabolic genetic risk score was calculated by counting 15 risk alleles associated with hypertension, diabetes, or dyslipidemia. Data were analyzed using linear mixed-effects and Cox proportional-hazards models, adjusting for age, sex, and education.Results:The study sample consisted of 317 participants (age ≥60 years; 61.8% women). Favorable and intermediate (vs. unfavorable) global CVH profiles were related to slower WMH progression, with β-coefficients (95% CI) being -0.019(-0.035–-0.002) and -0.018(-0.034–-0.001), respectively. Favorable and intermediate (vs. unfavorable) biological CVH profiles were significantly related to slower WMH increase only in people aged 60-72 years. CVH profiles were not related to progression of other brain measures. Furthermore, a higher metabolic genetic risk score (range: 6-21) was associated with faster WMH increase (β-coefficient=0.005; 95% CI: 0.003–0.008). There were statistical interactions of metabolic genetic risk score with global and behavioral CVH profiles on WMH accumulation. A higher metabolic genetic risk score was related to faster WMH accumulation, with β-coefficients being 0.015(0.007–0.023), 0.005(0.001–0.009), and 0.003(-0.001–0.006) among people with unfavorable, intermediate, and favorable global CVH profiles, respectively; the corresponding β-coefficients were 0.013(0.006–0.020), 0.006(0.003–0.009), and 0.002(-0.002–0.006) among people with unfavorable, intermediate, and favorable behavioral CVH profiles.Discussion:Intermediate-to-favorable global CVH profiles in older adults are associated with slower vascular brain aging. The association of metabolic genetic risk load with accelerated vascular brain aging was evident among people with unfavorable-to-intermediate, but not favorable, CVH profiles. These findings highlight the importance of adhering to favorable CVH profiles, especially healthy behaviors, in vascular brain health.

Machine‐learning‐derived heart and brain age are independently associated with cognition

“…One view is that a higher BDA is an indicator of accelerated brain aging that has accumulated over an individual's lifetime [35]; another postulates that individuals vary in their brain and body health from the beginning of life [36,37]. Both perspectives are supported by the results of empirical studies; perinatal variables (birth weight) and genetic variability are associated with BDA [36,38] Vascular risk factors may be reflected in features seen on brain MRI, for example global white matter hyperintensities [42,43], which may not be fully captured by the DNN algorithm of BDA.…”

“…This indicates that vascular dysfunction is not necessarily reflected in morphological structures of the brain, at least not at the time point when the measurements of HDA and BDA were conducted in our population‐based sample. Vascular risk factors may be reflected in features seen on brain MRI, for example global white matter hyperintensities [42, 43], which may not be fully captured by the DNN algorithm of BDA.…”

The age‐dependent association of Life's Simple 7 with transitions across cognitive states after age 60

“…Poor CVH has previously been related to greater white matter hyperintensity volume, silent brain infarcts, lower gray matter perfusion, and lower brain volume, which may mediate the association between CVH and cognitive function [29, 30]. In addition, a recent study showed that LS7 was related to levels of cerebrospinal Alzheimer's disease biomarkers, suggesting a link between better CVH and a lower degree of Alzheimer's disease pathology [31].…”