Sex differences in risk factors for white matter hyperintensities in non-demented older individuals

Alqarni, Abdullah; Jiang, Jiyang; Crawford, John D.; Koch, Forrest; Brodaty, Henry; Sachdev, Perminder S.; Wang, Wen

doi:10.1016/j.neurobiolaging.2020.11.001

Cited by 46 publications

(62 citation statements)

References 50 publications

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“…Though strong edges were visible between MetS components in females as in males, relationships between WMH and metabolic syndrome components were weak. This finding is consistent with the findings discussed previously on sex differences in white matter burden (Pasha et al, 2018b ; Alqarni et al, 2021 ). Most notable was the centrality of ApoE and age in the graphical model of the female network.…”

Section: Discussionsupporting

confidence: 94%

“…Consistent with prior research (Pasha et al, 2018b ), the network for males revealed greater interconnectedness between metabolic risk factors and white matter hyperintensities. Additionally, though one study found women to have higher levels of WMH than men overall, higher BMI was associated with higher WMH only in men (Alqarni et al, 2021 ), providing further support for sex differences in the relationship between metabolic risk factors and WMH. HDL cholesterol and waist circumference appear to be of particular importance for males as this node had the highest level of betweenness.…”

Section: Discussionmentioning

confidence: 97%

“…Relationships between WMH and cardiometabolic risk at midlife have been observed in both cross-sectional (Pasha et al, 2017 ) and longitudinal follow-up studies (Aljondi et al, 2020 ). Additionally, relationships between WMH, cardiovascular risk factors, and later life cognitive decline are marked by sex differences (Pasha et al, 2018b ; Burke et al, 2019 ; Alqarni et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

“…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%

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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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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 97%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Network Modeling Sex Differences in Brain Integrity and Metabolic Health

Foret

Dekhtyar

Cole

et al. 2021

Front. Aging Neurosci.

View full text Add to dashboard Cite

show abstract

“…Mounting evidence shows that periventricular WMH (PVWMH) and deep WMH (DWMH) which are two subclassifications of WMH have different neuropathology, risk factors, associations with cognition (Sachdev et al, 2005), and different genetic underpinnings (Armstrong et al, 2020). In addition, GM and WMH volumes also show sex differences (Alqarni et al, 2021; Liu et al, 2020; Lotze et al, 2019; Sachdev et al, 2009b). Therefore, the empirical evidence indicates that GM and WMH volumes are well-established brain neuroimaging metrics associated with brain ageing.…”

Section: Introductionmentioning

confidence: 99%

Parental lifespan and polygenic risk score of longevity are associated with white matter hyperintensities

Dong

Thalamuthu

Jiang

et al. 2021

Preprint

Self Cite

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Human longevity is moderately heritable and is hence influenced by both genetic and environmental factors. However, there remains considerable uncertainty regarding its relationship with brain ageing. In this study, we investigated the associations of parental lifespan (parental age at death) and polygenic risk score for longevity (longevity-PRS) with structural magnetic resource imaging (MRI) brain metrics considered to reflect the brain ageing process. We used a discovery sample (N = 19136) from the UK Biobank and a replication sample (N =809) from the Sydney Memory and Ageing Study and the Older Australian Twins Study. We found lower cerebral white matter hyperintensity (WMH) volumes to be significantly associated with longer parental lifespan in the discovery and replication samples and higher longevity-PRS in the discovery sample and a similar trend in the replication sample. The association of longevity-PRS with WMH remained significant after removing the influence of the apolipoprotein E locus. Additionally, the effects of longevity-PRS on the association were more prominent in males, especially in the older-male group. Our findings suggest that human longevity-related genes may have an influence on WMH burden, suggesting WMH volume may be a biomarker for longevity and an ageing endophenotype.

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Sex differences in risk factors, burden, and outcomes of cerebrovascular disease in Alzheimer's disease populations

Morrison,

Dadar,

Collins

2023

Alzheimer's & Dementia

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BACKGROUNDWhite matter hyperintensities (WMHs) are associated with cognitive decline and progression to mild cognitive impairment (MCI) and dementia. It remains unclear if sex differences influence WMH progression or the relationship between WMH and cognition.METHODSLinear mixed models examined the relationship between risk factors, WMHs, and cognition in males and females.RESULTSMales exhibited increased WMH progression in occipital, but lower progression in frontal, total, and deep than females. For males, history of hypertension was the strongest contributor, while in females, the vascular composite was the strongest contributor to WMH burden. WMH burden was more strongly associated with decreases in global cognition, executive functioning, memory, and functional activities in females than males.DISCUSSIONControlling vascular risk factors may reduce WMH in both males and females. For males, targeting hypertension may be most important to reduce WMHs. The results have implications for therapies/interventions targeting cerebrovascular pathology and subsequent cognitive decline.HIGHLIGHTS Hypertension is the main vascular risk factor associated with WMH in males A combination of vascular risk factors contributes to WMH burden in females Only small WMH burden differences were observed between sexes Females’ cognition was more negatively impacted by WMH burden than males Females with WMHs may have less resilience to future pathology

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Sex differences in risk factors for white matter hyperintensities in non-demented older individuals

Cited by 46 publications

References 50 publications

Network Modeling Sex Differences in Brain Integrity and Metabolic Health

Network Modeling Sex Differences in Brain Integrity and Metabolic Health

Parental lifespan and polygenic risk score of longevity are associated with white matter hyperintensities

Sex differences in risk factors, burden, and outcomes of cerebrovascular disease in Alzheimer's disease populations

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