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August 17, 2022Research Article

Associations of Sex, Age, and Cardiometabolic Risk Profiles With Brain Structure and Cognition: A UK Biobank Latent Class Analysis

View ORCID ProfileStephanie Than, View ORCID ProfileChris Moran, View ORCID ProfileTaya A Collyer, Richard J Beare, Emma M Lane, Amanda J Vincent, Wei Wang, Michele L Callisaya, Russell Thomson, View ORCID ProfileThanh G Phan, Alex Fornito, Velandai K Srikanth
First published August 17, 2022, DOI: https://doi.org/10.1212/WNL.0000000000201028
Stephanie Than
1Peninsula Clinical School, Monash University, Melbourne, Victoria, Australia
2National Centre for Healthy Ageing, Melbourne, Australia
3Department of Geriatric Medicine, Peninsula Health, Melbourne, Victoria, Australia
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  • ORCID record for Stephanie Than
Chris Moran
1Peninsula Clinical School, Monash University, Melbourne, Victoria, Australia
2National Centre for Healthy Ageing, Melbourne, Australia
3Department of Geriatric Medicine, Peninsula Health, Melbourne, Victoria, Australia
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  • ORCID record for Chris Moran
Taya A Collyer
1Peninsula Clinical School, Monash University, Melbourne, Victoria, Australia
2National Centre for Healthy Ageing, Melbourne, Australia
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  • ORCID record for Taya A Collyer
Richard J Beare
1Peninsula Clinical School, Monash University, Melbourne, Victoria, Australia
2National Centre for Healthy Ageing, Melbourne, Australia
4Murdoch Children’s Research Institute, Melbourne, Victoria, Australia
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Emma M Lane
1Peninsula Clinical School, Monash University, Melbourne, Victoria, Australia
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Amanda J Vincent
5Monash Centre for Health Research and Implementation, Monash University, Melbourne, Victoria, Australia
6Department of Endocrinology, Monash Health, Melbourne, Victoria, Australia
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Wei Wang
1Peninsula Clinical School, Monash University, Melbourne, Victoria, Australia
7Monash Department of Clinical Epidemiology, Cabrini Institute, Melbourne, Victoria, Australia
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Michele L Callisaya
1Peninsula Clinical School, Monash University, Melbourne, Victoria, Australia
2National Centre for Healthy Ageing, Melbourne, Australia
8Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia
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Russell Thomson
9Centre for Research in Mathematics, Western Sydney University, Sydney, New South Wales, Australia
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Thanh G Phan
10Stroke and Aging Research Group, Monash University, Melbourne, Victoria, Australia
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  • ORCID record for Thanh G Phan
Alex Fornito
11The Turner Institute for Brain and Mental Health, Monash University, Melbourne, Victoria, Australia;
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Velandai K Srikanth
1Peninsula Clinical School, Monash University, Melbourne, Victoria, Australia
2National Centre for Healthy Ageing, Melbourne, Australia
3Department of Geriatric Medicine, Peninsula Health, Melbourne, Victoria, Australia
8Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia
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Citation
Associations of Sex, Age, and Cardiometabolic Risk Profiles With Brain Structure and Cognition: A UK Biobank Latent Class Analysis
Stephanie Than, Chris Moran, Taya A Collyer, Richard J Beare, Emma M Lane, Amanda J Vincent, Wei Wang, Michele L Callisaya, Russell Thomson, Thanh G Phan, Alex Fornito, Velandai K Srikanth
Neurology Aug 2022, 10.1212/WNL.0000000000201028; DOI: 10.1212/WNL.0000000000201028

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Abstract

Objectives: It is unknown whether there are sex-related profiles of cardiometabolic health that contribute differently to age-related changes in brain health during midlife. We studied how latent classes of middle-aged individuals clustering by age, sex, menopause and cardiometabolic health were associated with brain structure and cognitive performance.

Methods: Health, brain and abdominal magnetic resonance imaging (MRI) data from the UK Biobank cohort (men and women >40 years in the United Kingdom) were used. We applied latent class analysis to identify groups of individuals based on age, sex, menopausal status and cardiometabolic health. We examined associations of class membership with brain volumes (total brain [TBV], grey matter [GMV], white matter [WMV], hippocampal [HV], white matter hyperintensities [WMHV]) and cognitive performance.

Results: Data were available for 36,420 individuals (mean age 64.9 years, 48.5% women). Eight latent classes differing in age, sex and cardiometabolic risk were identified. Class 1 (reference class) included individuals with the lowest probability of older age and cardiometabolic risk, and they had the most positive associations with cognitive function and brain volumes. In those aged >60, but not in those aged 50-60 years, the negative associations of age with TBV, GMV and WMV were greater in the class comprising healthier older women than classes comprising older men of varying cardiometabolic and vascular health. There were no age-class interactions for cognitive test performance.

Conclusions: Latent class analysis detected groups of middle-aged individuals clustering by cardiometabolic health. The relationship of age with brain volumes varies by sex, menopausal status and cardiometabolic health profile.

  • Received January 25, 2022.
  • Accepted in final form June 13, 2022.
  • © 2022 American Academy of Neurology

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