Sex moderates the relationship between aortic stiffness, cognition and cerebrovascular reactivity in healthy older adults

Sabra, Dalia; Intzandt, Brittany; Desjardins-Crépeau, Laurence; Langeard, Antoine; Steele, Christopher J.; Frouin, F.; Hoge, Richard D.; Bherer, Louis; Gauthier, Claudine

doi:10.1101/2020.02.18.955146

Cited by 1 publication

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References 192 publications

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“…Sex has emerged as a moderator in many associations between brain health and cardiometabolic dysfunction. More specifically, sex appears to moderate associations between cognition and aortic stiffness (Sabra et al, 2020 ), between risk of dementia and plasma lipid and lipropoteins (Ancelin et al, 2013 ; Gilsanz et al, 2017 ), and between white matter hyperintensities and adiposity (Alqarni et al, 2021 ). Additionally, there are pronounced sex differences in cardiovascular aging, particularly in the structures and function of the vasculature (Merz and Cheng, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Network Modeling Sex Differences in Brain Integrity and Metabolic Health

Foret

Dekhtyar

Cole

et al. 2021

Front. Aging Neurosci.

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Hypothesis-driven studies have demonstrated that sex moderates many of the relationships between brain health and cardiometabolic disease, which impacts risk for later-life cognitive decline. In the present study, we sought to further our understanding of the associations between multiple markers of brain integrity and cardiovascular risk in a midlife sample of 266 individuals by using network analysis, a technique specifically designed to examine complex associations among multiple systems at once. Separate network models were constructed for male and female participants to investigate sex differences in the biomarkers of interest, selected based on evidence linking them with risk for late-life cognitive decline: all components of metabolic syndrome (obesity, hypertension, dyslipidemia, and hyperglycemia); neuroimaging-derived brain-predicted age minus chronological age; ratio of white matter hyperintensities to whole brain volume; seed-based resting state functional connectivity in the Default Mode Network, and ratios of N-acetyl aspartate, glutamate and myo-inositol to creatine, measured through proton magnetic resonance spectroscopy. Males had a sparse network (87.2% edges = 0) relative to females (69.2% edges = 0), indicating fewer relationships between measures of cardiometabolic risk and brain integrity. The edges in the female network provide meaningful information about potential mechanisms between brain integrity and cardiometabolic health. Additionally, Apolipoprotein ϵ4 (ApoE ϵ4) status and waist circumference emerged as central nodes in the female model. Our study demonstrates that network analysis is a promising technique for examining relationships between risk factors for cognitive decline in a midlife population and that investigating sex differences may help optimize risk prediction and tailor individualized treatments in the future.

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