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Midlife Cardiovascular Fitness Is Reflected in the Brain's White Matter.

ABSTRACT: Disappointing results from clinical trials designed to delay structural brain decline and the accompanying increase in risk for dementia in older adults have precipitated a shift in testing promising interventions from late in life toward midlife before irreversible damage has accumulated. This shift, however, requires targeting midlife biomarkers that are associated with clinical changes manifesting only in late life. Here we explored possible links between one putative biomarker, distributed integrity of brain white matter, and two intervention targets, cardiovascular fitness and healthy lifestyle behaviors, in midlife. At age 45, fractional anisotropy (FA) derived from diffusion weighted MRI was used to estimate the microstructural integrity of distributed white matter tracts in a population-representative birth cohort. Age-45 cardiovascular fitness (VO₂Max; N = 801) was estimated from heart rates obtained during submaximal exercise tests; age-45 healthy lifestyle behaviors were estimated using the Nyberg Health Index (N = 854). Ten-fold cross-validated elastic net predictive modeling revealed that estimated VO₂Max was modestly associated with distributed FA. In contrast, there was no significant association between Nyberg Health Index scores and FA. Our findings suggest that cardiovascular fitness levels, but not healthy lifestyle behaviors, are associated with the distributed integrity of white matter in the brain in midlife. These patterns could help inform future clinical intervention research targeting ADRDs.

SUBMITTER: d'Arbeloff T

PROVIDER: S-EPMC8055854 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Midlife Cardiovascular Fitness Is Reflected in the Brain's White Matter.

d'Arbeloff Tracy T Elliott Maxwell L ML Knodt Annchen R AR Sison Maria M Melzer Tracy R TR Ireland David D Ramrakha Sandhya S Poulton Richie R Caspi Avshalom A Moffitt Terrie E TE Hariri Ahmad R AR

Frontiers in aging neuroscience 20210406

Disappointing results from clinical trials designed to delay structural brain decline and the accompanying increase in risk for dementia in older adults have precipitated a shift in testing promising interventions from late in life toward midlife before irreversible damage has accumulated. This shift, however, requires targeting midlife biomarkers that are associated with clinical changes manifesting only in late life. Here we explored possible links between one putative biomarker, distributed i ...[more]

PMID: 33889085

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Project description:Background and objectivesThe menopause transition is increasingly recognized as a time of importance for women's brain health. A growing body of work indicates that the classic menopausal symptom, vasomotor symptom (VMS), may be associated with poorer cardiovascular health. Other work links VMS to poorer cognition. We investigate whether VMS, when rigorously assessed using physiologic measures, are associated with greater white matter hyperintensity volume (WMHV) among midlife women. We consider a range of potential explanatory factors in these associations and explore whether VMS are associated with the spatial distribution of WMHV.MethodsWomen aged 45-67 years and free of hormone therapy underwent 24 hours of physiologic VMS monitoring (sternal skin conductance), actigraphy assessment of sleep, physical measures, phlebotomy, and 3 Tesla neuroimaging. Associations between VMS (24-hour, wake, and sleep VMS, with wake and sleep intervals defined by actigraphy) and whole brain WMHV were considered in linear regression models adjusted for age, race, education, smoking, body mass index, blood pressure, insulin resistance, and lipids. Secondary models considered WMHV in specific brain regions (deep, periventricular, frontal, temporal, parietal, and occipital) and additional covariates including sleep.ResultsThe study sample included 226 women. Physiologically assessed VMS were associated with greater whole brain WMHV in multivariable models, with the strongest associations observed for sleep VMS (24-hour VMS, B[SE] = 0.095 [0.045], p = 0.032; Wake VMS, B[SE] = 0.078 [0.046], p = 0.089, Sleep VMS, B[SE] = 0.173 [0.060], p = 0.004). Associations were not accounted for by additional covariates including actigraphy-assessed sleep (wake after sleep onset). When considering the spatial distribution of WMHV, sleep VMS were associated with both deep WMHV, periventricular WMHV, and frontal lobe WMHV.DiscussionVMS, particularly VMS occurring during sleep, were associated with greater WMHV. Identification of female-specific midlife markers of poor brain health later in life is critical to identify women who warrant early intervention and prevention. VMS have the potential to serve as female-specific midlife markers of brain health in women.

Project description:ObjectiveElevated inflammation is associated with worse late-life cognitive functioning and brain health. Our goal was to examine the relationship between inflammation trajectories and white matter integrity in midlife.MethodsParticipants were 508 adults from the Coronary Artery Risk Development in Young Adults Study (CARDIA; 51% female). Latent class analysis was used to identify inflammation trajectories based on repeated measures of the inflammatory marker C-reactive protein (CRP) over the 18 years before brain magnetic resonance imaging (MRI). Outcomes were brain MRI measures of total and region-specific white matter volume and integrity at a mean age of 50.6 ± 3.4 years. Linear regression was used to examine if inflammation trajectories were associated with brain MRI outcomes, adjusting for potential confounds in all models and for disease and health behaviors in follow-up models.ResultsLower-stable (38%), moderate-increasing (7%), and consistently-higher (54%), trajectories emerged. Compared to the lower-stable group, the moderate-increasing group showed lower white matter volume (β = -0.18, 95% CI -0.29, -0.06) and worse white matter integrity as indexed by lower fractional anisotropy (FA; β = -0.37, 95% CI -0.70, -0.04) and higher mean diffusivity (β = 0.44, 95% CI 0.11, 0.78) in the whole brain. The consistently-higher group showed lower whole-brain FA (β = -0.20, -0.38, -0.03). In exploratory analyses, the moderate-increasing group showed lower white matter volume, lower FA and higher MD in the frontal, temporal, and parietal lobes compared to the lower-stable group. The consistently-higher group showed lower white matter volume in the parietal lobe and lower FA in the frontal, temporal, and parietal lobes, but similar MD, compared to the lower-stable group. Findings for the moderate-increasing, but not the consistently-higher, group were robust to adjustment for disease and lifestyle factors.ConclusionIncreasing or high inflammation trajectories from early to mid adulthood are associated with worse brain health, as indexed by lower white matter volume and/or worse white matter integrity.

Project description:In this study, we perform a region of interest diffusion tensor imaging and advanced diffusion complexity analysis of normal appearing white matter to determine the impact of vascular health on these diffusivity metrics in midlife adults. 77 participants (26 black, 35 female) at year 30 visit in the Coronary Artery Risk Development in Young Adults longitudinal study were scanned with an advanced diffusion-weighted imaging and fluid-attenuated inversion recovery protocol. Fractional anisotropy and non-linear diffusion complexity measures were estimated. Cumulative measures across 30 years (9 study visits) of systolic blood pressure, body mass index, glucose, smoking and cholesterol were calculated as the area under the curve from baseline up to year 30 examination. Partial correlation analyses assessed the association between cumulative vascular health measures and normal appearing white matter diffusion metrics in these participants. Midlife normal appearing white matter diffusion properties were significantly associated (P < 0.05) with cumulative exposure to vascular risk factors from young adulthood over the 30-year time period. Higher cumulative systolic blood pressure exposure was associated with increased complexity and decreased fractional anisotropy. Higher cumulative body mass index exposure was associated with decreased fractional anisotropy. Additionally, in the normal appearing white matter of black participants (P < 0.05), who exhibited a higher cumulative vascular risk exposure, fractional anisotropy was lower and complexity was higher in comparison to normal appearing white matter in white participants. Higher burden of vascular risk factor exposure from young adulthood to midlife is associated with changes in the diffusion properties of normal appearing white matter in midlife. These changes which may reflect axonal disruption, increased inflammation and/or increased glial proliferation, were primarily observed in both anterior and posterior normal appearing white matter regions of the corpus callosum. These results suggest that microstructural changes in normal appearing white matter are sensitive to vascular health during young adulthood and are possibly therapeutic targets in interventions focused on preserving white matter health across life.

Dataset Information

Midlife Cardiovascular Fitness Is Reflected in the Brain's White Matter.

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Midlife Cardiovascular Fitness Is Reflected in the Brain's White Matter.

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