Cardiovascular risk and obesity impact loss of grey matter volume earlier in males than females.

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.