| Application: | 24954, Cardiometabolic and genetic determinants of brain structure and function - a focus on obesity, type 2 diabetes and associated factors |
| Title: | Interactions Between Age, Sex, Menopause, and Brain Structure at Midlife: A UK Biobank Study |
| Size: | 7.1 MB |
| Archived: | 17 Sep 2021 |
| Stability: | Complete |
| Personal: | No individual-level data |
Return 3842
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Notes
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 ( = 5.35 mL/year) than in men ( = 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 ( = 5.89 mL/year) than in pre/perimenopausal women ( = 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
Application 24954
Cardiometabolic and genetic determinants of brain structure and function - a focus on obesity, type 2 diabetes and associated factors
This study aims to study the relative contribution of obesity, cardiometabolic factors and genetic factors to the development of brain dysfunction. The emphasis is on the role of obesity, prediabetes, type 2 diabetes, and their associated factors as exposures. Common factors predisposing to metabolic dysfunction and dementia will be of main interest. The outcomes will be structural and functional measures (cognitive and imaging. The role of sex/gender in modifying these relationships will be evaluated This body of research will shed new light on mechanisms underlying the associations between two highly prevalent disorders (diabetes and dementia), both major public health problems It relates to the major public health disorders of obesity, diabetes and dementia - hence is health-related and in the public interest. Our group has substantial expertise in the field of ageing, advanced imaging analysis, dementia and cognitive dysfunction related to diabetes. Data from the UK biobank will be collated for exposure and confounding/modifying variables. Imaging analyses will be conducted using both existing processed data and with in-house methods to generate outcome variables. Associations of interest will be examined using a combination of simple and advanced analytical methods. Data arising from these analyses will be presented at scientific conferences, and published in peer-reviewed literature. Given that we are aiming to assess the magnitude of relative contributions of the exposure factors, to explore effect modification and interaction, and to use advanced analytical techniques (including graph/network analyses) - this would require a substantial dataset given the levels of stratification required. The primary dataset includes all people with measured cognitive function, brain imaging, genomics and body composition. Available data on brain imaging in this sample will also be required. Additionally,data are required on relevant demographic, psychosocial, lifestyle,c ardiovascular, genes (SNPs), and already available blood biomarkers collected and analysed in the UK Biobank - reflecting factors relevant to linking obesity, diabetes and dementia.
| Lead investigator: | Professor Velandai Srikanth |
| Lead institution: | Monash University |
1 Publication
| Pub ID | Title | Author(s) | Year | Journal |
|---|---|---|---|---|
| 3843 | Interactions Between Age, Sex, Menopause, and Brain Structure at Midlife: A UK Biobank Study | Stephanie Than (+10) | 2020 | The Journal of Clinical Endocrinology & Metabolism |
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