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Abstract
Background It remains imperative to discover the time course that cardiovascular risk factors influence neurodegeneration in males and females and decipher whether the apolipoprotein (APOE) genotype mediates this relationship. Here we perform a large-scale evaluation of the influence of cardiovascular risk and obesity on brain volume in males and females in different age groups.
Methods 34 425 participants between the ages of 45 and 82 years were recruited from the UK Biobank database https://www.ukbiobank.ac.uk. T1-weighted structural MR images (n=34 425) were downloaded locally for all participants, and voxel-based morphometry was performed to characterise the volumetric changes of the whole brain. The influence of Framingham cardiovascular risk (general cardiovascular risk), abdominal subcutaneous adipose tissue, and visceral adipose tissue volume (obesity) on cortical grey matter volume across different decades of life was evaluated with voxel-wise analysis.
Results In males, cardiovascular risk and obesity demonstrated the greatest influence on lower grey matter volume between 55–64 years of age. Female participants showed the greatest effect on lower grey matter volume between 65–74 years of age. Associations remained significant in APOE ε4 carriers and APOE ε4 non-carriers when evaluated separately.
Conclusions The strongest influence of cardiovascular risk and obesity on reduced brain volume was between 55–64 years of age in males, whereas women were most susceptible to the detrimental effects of cardiovascular risk a decade later between 65–74 years of age. Here we elucidate the timing that targeting cardiovascular risk factors and obesity should be implemented in males and females to prevent neurodegeneration and Alzheimer’s disease development.
- ALZHEIMER'S DISEASE
- CEREBROVASCULAR DISEASE
- METABOLIC DISEASE
- MRI
Data availability statement
Data may be obtained from a third party and are not publicly available. These data are available upon approved research from UK Biobank https://www.ukbiobank.ac.uk/. Data include a range of imaging, genetic, clinical, and demographic information on 500,000 participants. UK Biobank data are available to all bona fide researchers for all types of health-related research which is in the public interest. Researchers must register with UK Biobank by completing the registration form in the Access Management System (https://ams.ukbiobank.ac.uk/ams/).
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Data availability statement
Data may be obtained from a third party and are not publicly available. These data are available upon approved research from UK Biobank https://www.ukbiobank.ac.uk/. Data include a range of imaging, genetic, clinical, and demographic information on 500,000 participants. UK Biobank data are available to all bona fide researchers for all types of health-related research which is in the public interest. Researchers must register with UK Biobank by completing the registration form in the Access Management System (https://ams.ukbiobank.ac.uk/ams/).
Footnotes
Contributors JN, SG, and PE generated the concept and design of the study. JN performed all data analysis and wrote the manuscript. All authors commented on the final version of the manuscript. PE attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. PE is the guarantor.
Funding JN was funded by the Imperial College London President’s PhD scholarship.
Disclaimer Dissemination to participants and related patient and public communities. Results from UK Biobank are routinely disseminated to study participants via the study website and Twitter feed.
Competing interests All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf. We have read and understood the BMJ policy on declaration of interests and declare the following interests: PE was funded by the Medical Research Council and now by Higher Education Funding Council for England (HEFCE). He has also received grants from Alzheimer’s Research, UK, Alzheimer’s Drug Discovery Foundation, Alzheimer’s Society, UK, Medical Research Council, Alzheimer’s Association US, Van-Geest foundation, and European Union grants. PE is a consultant to Roche, Pfizer, and Novo Nordisk. He has received educational and research grants from GE Healthcare, Novo Nordisk, Piramal Life Science/Life Molecular Imaging, Avid Radiopharmaceuticals and Eli Lilly. He was a member of the Scientific Advisory Board at Novo Nordisk.
Provenance and peer review Not commissioned; externally peer reviewed.