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The effect of midlife cardiovascular risk factors on white matter hyperintensity volume and cognition two decades later in normal ageing women


Cerebral White Matter Hyperintensity (WMH) lesions have been identified as markers of cerebrovascular diseases and they are associated with increased risk of cognitive impairment. In this study, we investigated the relationship between midlife cardiovascular risk factors and late life WMH volumes two decades later, and examined their association with cognitive performance. 135 participants from the Women’s Healthy Ageing Project had completed midlife cardiovascular risk measurement in 1992 and late life brain MRI scan and cognitive assessment in 2012. In these community-dwelling normal aging women, we found that higher midlife Framingham Cardiovascular Risk Profile (FCRP) score was associated with greater WMH volume two decades later, and was predominantly driven by the impact of HDL cholesterol level, controlling for age, education and APOE ε4 status. Structural equation modelling demonstrated that the relationship between midlife FCRP score and late life executive function was mediated by WMH volume. These findings suggest intervention strategies that target major cardiovascular risk factors at midlife might be effective in reducing the development of WMH lesions and thus late life cognitive decline.

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We would like to acknowledge the contribution of the participants and their supporters who have contributed their time and commitment for over 20 years to the University. A full list of all researchers contributing to the project and the membership of our Scientific Advisory Board is available at http://www.medrmhwh.unimelb.edu.au/Research/WHAP.html.


This study is funded by the National Health and Medical Research Council (NHMRC Grants 547500, 1032350 & 1062133), Ramaciotti Foundation, Australian Healthy Ageing Organisation, the Brain Foundation, the Alzheimer’s Association (NIA320312), Australian Menopausal Society, Bayer Healthcare, Shepherd Foundation, Scobie and Claire Mackinnon Foundation, Collier Trust Fund, J.O. & J.R. Wicking Trust, Mason Foundation and the Alzheimer’s Association of Australia. Inaugural funding was provided by VicHealth and the NHMRC. The Principal Investigator of WHAP (CSz) is supported by the National Health and Medical Research Council.

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Correspondence to Cassandra Szoeke.

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Dr. Szoeke has provided clinical consultancy and been on scientific advisory committees for the Australian Commonwealth Scientific and Industrial Research Organisation, Alzheimer’s Australia, University of Melbourne and other relationships which are subject to confidentiality clauses. She has been a named Chief Investigator on investigator driven collaborative research projects in partnership with Pfizer, Merck, Bayer and GE. She has been an investigator on clinical trials with Lundbeck within the last 2 years. Dr. Desmond has supported by the Royal Melbourne Hospital and the National Health and Medical Research Council of Australia. Other authors report no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Aljondi, R., Szoeke, C., Steward, C. et al. The effect of midlife cardiovascular risk factors on white matter hyperintensity volume and cognition two decades later in normal ageing women. Brain Imaging and Behavior 14, 51–61 (2020). https://doi.org/10.1007/s11682-018-9970-5

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  • Midlife cardiovascular risk factors
  • Framingham cardiovascular risk profile score
  • White matter hyperintensity volume
  • Cognitive domains
  • Elderly women