Interactions Between Age, Sex, Menopause, and Brain Structure at Midlife: A UK Biobank Study

Abstract Objectives Age and female sex are risk factors for dementia, and menopause is associated with cognitive dysfunction. Previous work largely considered the effects of sex and menopause as being independent of age. We studied whether age interacts with sex or menopause in explaining imaging biomarkers of dementia during midlife. Methods In this cross-sectional study of UK Biobank participants with brain magnetic resonance imaging (MRI), we explored the interaction of age with sex or menopausal status in explaining total brain volume (TBV), gray matter volume (GMV), white matter volume (WMV), white matter hyperintensity volume (WMHV), regional cortical volume , and subcortical volume. Results Data were available for 1827 postmenopausal women, 230 pre/perimenopausal women and 2165 men (median age 63.3 years). There was a significant interaction between age and sex (P = .024) for TBV, where the inverse association age with TBV was steeper in women (β = –5.35 mL/year) than in men (β = –4.77 mL/year). Similar age–sex interactions were also observed for GMV and WMV. In women, there was a significant interaction between age and menopausal status (P = .007) where the inverse association of age with TBV was steeper in postmenopausal (β = –5.89 mL/year) than in pre/perimenopausal women (β = –1.61 mL/year). Similar age–menopause interactions were found in predicting lower GMV and higher WMHV. Differences in the direction of these age–sex and age–menopause interactions were found for regional cortical and subcortical brain volumes. Conclusion Sex and menopause both interact with age during midlife in explaining MRI biomarkers of dementia. Further work is required to understand the mechanisms driving these interactions to develop strategies for delaying dementia.

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Association between APOE e4 and white matter hyperintensity volume, but not total brain volume or white matter integrity

Brain Imaging and Behavior ◽

10.1007/s11682-019-00069-9 ◽

2019 ◽

Vol 14 (5) ◽

pp. 1468-1476 ◽

Cited By ~ 12

Author(s):

Donald M. Lyall ◽

Simon R. Cox ◽

Laura M. Lyall ◽

Carlos Celis-Morales ◽

Breda Cullen ◽

...

Keyword(s):

White Matter ◽

Cognitive Aging ◽

Social Deprivation ◽

Mean Diffusivity ◽

Brain Magnetic Resonance Imaging ◽

Smoking History ◽

White Matter Hyperintensity ◽

Future Research ◽

Uk Biobank ◽

Intermediate Phenotypes

Abstract Apolipoprotein (APOE) e4 genotype is an accepted risk factor for accelerated cognitive aging and dementia, though its neurostructural substrates are unclear. The deleterious effects of this genotype on brain structure may increase in magnitude into older age. This study aimed to investigate in UK Biobank the association between APOE e4 allele presence vs. absence and brain imaging variables that have been associated with worse cognitive abilities; and whether this association varies by cross-sectional age. We used brain magnetic resonance imaging (MRI) and genetic data from a general-population cohort: the UK Biobank (N = 8395 after exclusions). We adjusted for the covariates of age in years, sex, Townsend social deprivation scores, smoking history and cardiometabolic diseases. There was a statistically significant association between APOE e4 genotype and increased (i.e. worse) white matter (WM) hyperintensity volumes (standardised beta = 0.088, 95% confidence intervals = 0.036 to 0.139, P = 0.001), a marker of poorer cerebrovascular health. There were no associations with left or right hippocampal, total grey matter (GM) or WM volumes, or WM tract integrity indexed by fractional anisotropy (FA) and mean diffusivity (MD). There were no statistically significant interactions with age. Future research in UK Biobank utilising intermediate phenotypes and longitudinal imaging hold significant promise for this area, particularly pertaining to APOE e4’s potential link with cerebrovascular contributions to cognitive aging.

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SOCIOECONOMIC AND DEMOGRAPHIC INFLUENCES ON WHITE MATTER HYPERINTENSITY BURDEN IN THE UNITED KINGDOM: DATA FROM UK BIOBANK

10.26226/morressier.58e389b2d462b80292385173 ◽

2017 ◽

Author(s):

Caroline McHutchison

Keyword(s):

United Kingdom ◽

White Matter ◽

White Matter Hyperintensity ◽

Uk Biobank ◽

The United Kingdom

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The Effects of Longitudinal White Matter Hyperintensity Change on Cognitive Decline and Cortical Thinning over Three Years

Journal of Clinical Medicine ◽

10.3390/jcm9082663 ◽

2020 ◽

Vol 9 (8) ◽

pp. 2663

Author(s):

Seung Joo Kim ◽

Dong Kyun Lee ◽

Young Kyoung Jang ◽

Hyemin Jang ◽

Si Eun Kim ◽

...

Keyword(s):

Cognitive Impairment ◽

White Matter ◽

Cognitive Decline ◽

Dynamic Change ◽

Surrogate Marker ◽

Brain Magnetic Resonance Imaging ◽

Longitudinal Change ◽

White Matter Hyperintensity ◽

Cortical Thinning ◽

Automated Method

White matter hyperintensity (WMH) has been recognised as a surrogate marker of small vessel disease and is associated with cognitive impairment. We investigated the dynamic change in WMH in patients with severe WMH at baseline, and the effects of longitudinal change of WMH volume on cognitive decline and cortical thinning. Eighty-seven patients with subcortical vascular mild cognitive impairment were prospectively recruited from a single referral centre. All of the patients were followed up with annual neuropsychological tests and 3T brain magnetic resonance imaging. The WMH volume was quantified using an automated method and the cortical thickness was measured using surface-based methods. Participants were classified into WMH progression and WMH regression groups based on the delta WMH volume between the baseline and the last follow-up. To investigate the effects of longitudinal change in WMH volume on cognitive decline and cortical thinning, a linear mixed effects model was used. Seventy patients showed WMH progression and 17 showed WMH regression over a three-year period. The WMH progression group showed more rapid cortical thinning in widespread regions compared with the WMH regression group. However, the rate of cognitive decline in language, visuospatial function, memory and executive function, and general cognitive function was not different between the two groups. The results of this study indicated that WMH volume changes are dynamic and WMH progression is associated with more rapid cortical thinning.

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Associations of cigarette smoking with gray and white matter in the UK Biobank

10.31234/osf.io/wyvnm ◽

2019 ◽

Author(s):

Joshua Gray ◽

Matthew Thompson ◽

Chelsie Benca-Bachman ◽

Max Michael Owens ◽

Mikela Murphy ◽

...

Keyword(s):

White Matter ◽

Cigarette Smoking ◽

Gray Matter ◽

Brain Structure ◽

Mean Diffusivity ◽

Medial Lemniscus ◽

Uk Biobank ◽

Matter Volume ◽

Increased Risk ◽

The Uk

Chronic cigarette smoking is associated with increased risk for myriad health consequences including cognitive decline and dementia, but research on the link between smoking and brain structure is nascent. We assessed the relationship of cigarette smoking (ever smoked, cigarettes per day, and duration) with gray and white matter using the UK Biobank cohort (gray matter N = 19,615; white matter N = 17,760), adjusting for numerous demographic and health confounders. Ever smoked and duration were associated with smaller total gray matter volume. Ever smoked was associated with reduced volume of the right VIIIa cerebellum, as well as elevated white matter hyperintensity volumes. Smoking duration was associated with reduced total white matter volume. With regard to specific tracts, ever smoked was associated with reduced fractional anisotropy in the left cingulate gyrus part of the cingulum, left posterior thalamic radiation, and bilateral superior thalamic radiation and increased mean diffusivity in the middle cerebellar peduncle, right medial lemniscus, bilateral posterior thalamic radiation, and bilateral superior thalamic radiation. Overall, we found significant associations of cigarette exposure with global measures of gray and white matter. Furthermore, we found select associations of ever smoked, but not cigarettes per day or duration, with specific gray and white matter regions. These findings inform our understanding of the connections between smoking and variation in brain structure and clarify potential mechanisms of risk for common neurological sequelae.

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Mental Retardation, Periventricular white Matter Hyperintensity on Brain Magnetic Resonance Imaging, Retinitis Pigmentosa, Optic Atrophy: A New Genetic Syndrome

International Journal of Research Studies in Medical and Health Sciences ◽

10.22259/ijrsmhs.0506004 ◽

2020 ◽

Vol 5 (6) ◽

pp. 16-20

Author(s):

Aamir Jalal Al-Mosawi

Keyword(s):

Magnetic Resonance Imaging ◽

Mental Retardation ◽

White Matter ◽

Magnetic Resonance ◽

Optic Atrophy ◽

Brain Magnetic Resonance Imaging ◽

White Matter Hyperintensity ◽

Periventricular White Matter ◽

Resonance Imaging ◽

Genetic Syndrome

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P4-122: White matter hyperintensity exacerbates cortical gray matter volume reduction in Alzheimer's disease: A voxel-based morphometric study

Alzheimer s & Dementia ◽

10.1016/j.jalz.2011.05.2144 ◽

2011 ◽

Vol 7 ◽

pp. S747-S747

Author(s):

Young Chul Youn ◽

Ging-Yuek Hsiung ◽

Baik Seok Kee ◽

SangYun Kim

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

White Matter ◽

Gray Matter ◽

Gray Matter Volume ◽

Volume Reduction ◽

White Matter Hyperintensity ◽

Morphometric Study ◽

Matter Volume ◽

Cortical Gray Matter

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White Matter Hyperintensities and the Progression of Frailty—The Tasmanian Study of Cognition and Gait

The Journals of Gerontology Series A ◽

10.1093/gerona/glaa024 ◽

2020 ◽

Vol 75 (8) ◽

pp. 1545-1550

Author(s):

Timothy P Siejka ◽

Velandai K Srikanth ◽

Ruth E Hubbard ◽

Chris Moran ◽

Richard Beare ◽

...

Keyword(s):

White Matter ◽

Mixed Models ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Frailty Index ◽

Brain Magnetic Resonance Imaging ◽

Population Based ◽

White Matter Hyperintensity ◽

Intracranial Volume ◽

Population Based Study

Abstract Background The contribution of cerebral small vessel disease (cSVD) to the pathogenesis of frailty remains uncertain. We aimed to examine the associations between cSVD with progression of frailty in a population-based study of older people. Methods People aged between 60 and 85 years were randomly selected form the electoral roll to participate in the Tasmanian Study of Cognition and Gait. Participants underwent self-reported questionnaires, objective gait, cognitive and sensorimotor testing over three phases ranging between 2005 and 2012. These data were used to calculate a 41-item frailty index (FI) at three time points. Baseline brain magnetic resonance imaging was performed on all participants to measure cSVD. Generalized mixed models were used to examine associations between baseline cSVD and progression of frailty, adjusted for confounders of age, sex, level of education, and total intracranial volume. Results At baseline (n = 388) mean age was 72 years (SD = 7.0), 44% were female, and the median FI score was 0.20 (interquartile range [IQR] 0.12, 0.27). In fully adjusted models higher burden of baseline white matter hyperintensity (WMH) was associated with frailty progression over 4.4 years (β = 0.03, 95% CI: 0.01, 0.05; p = .004) independent of other SVD markers. Neither baseline infarcts (p = .23), nor microbleeds at baseline (p = .65) were associated with progression of frailty. Conclusions We provide evidence for an association between baseline WMHs and progression of frailty. Our findings add to a growing body of literature suggesting WMH is a marker for frailty.

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CHA2DS2-VASc score, cerebral small vessel disease, and frailty in older patients with atrial fibrillation

Scientific Reports ◽

10.1038/s41598-020-75256-6 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Jung-Yeon Choi ◽

Leonard Sunwoo ◽

Sun-wook Kim ◽

Kwang-il Kim ◽

Cheol-Ho Kim

Keyword(s):

Atrial Fibrillation ◽

White Matter ◽

High Risk ◽

Gait Speed ◽

Structural Changes ◽

Brain Volume ◽

Frailty Index ◽

Brain Magnetic Resonance Imaging ◽

White Matter Hyperintensity ◽

Physical Frailty

Abstract The CHA2DS2-VASc score is a validated predictor of ischemic stroke in atrial fibrillation (AF) patients. However, data are limited on whether the CHA2DS2-VASc score is associated with subclinical brain structural changes or physical frailty among older AF patients. We assessed the relationship between CHA2DS2-VASc scores and brain structural changes or physical frailty in AF patients without history of stroke. Overall, 117 patients completed a comprehensive geriatric assessment for physical frailty. In brain magnetic resonance imaging sub-study (n = 49), brain volume and white matter hyperintensity lesion burden were automatically quantified using the LESIONQUANT software program. Patients with high risk of CHA2DS2-VASc scores (≥ 2 in men or ≥ 3 in women) tended to be older and had more comorbidities, higher frailty index, and slower gait speed. Total white matter hyperintensity lesion burden was higher in those with high risk of CHA2DS2-VASc score than in those with intermediate risk (score of 1 in men or 2 in women) of CHA2DS2-VASc score (1.67 [interquartile range: 0.70–3.45] vs. 0.64 [0.19–1.44], p = 0.036). Cognitive function was associated with brain volume, but gait speed was related with white matter hyperintensity lesion burden. In conclusion, we showed a positive relationship between CHA2DS2-VASc scores, white matter hyperintensity lesion burden, and physical frailty in older AF patients. Subclinical brain changes associated with high CHA2DS2-VASc scores may predict physical frailty risk.

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