CV risk and obesity associated with reduced brain volume earlier in males than females

The detrimental influence of cardiovascular (CV) risk and obesity on grey matter volume impacts males a decade earlier than females, a recent UK study has found.

Data from the UK Biobank database was utilized to analyze the influence of CV risk as well as abdominal fat and visceral obesity on neurodegeneration among different age groups in 34,425 participants (15,885 males) between the ages of 45 and 82 years. T1-weighted MRI brain scans and abdominal MRI scans of the participants were used for the study. [J Neurol Neurosurg Psychiatry 2024;doi:10.1136/jnnp-2024-333675]

The Framingham risk score, which provides a sex-specific risk prediction algorithm, was utilized as a marker of CV risk to investigate the relationship with neurodegeneration, as indicated by the association with grey matter volume. Voxel-based morphometry (VBM), a neuroimaging technique that enables detection of changes in brain volume through voxelwise statistical evaluation of multiple brain images, was conducted on all T1-weighted MRI scans to perform voxel-level analysis between CV risk and brain atrophy. Abdominal subcutaneous adipose tissue and visceral adipose tissue volumes were obtained using MRI, the gold standard of measuring body fat composition. In addition, visceral and subcutaneous fat measurements were used to provide a reliable marker of obesity and apolipoprotein E (APOE) genotype to assess whether the presence of ε4 allele modulates the relationship between CV risk and neurodegeneration.

The strongest influence of CV risk and obesity on neurodegeneration was observed at the ages of 55–74 years in males and 65–74 years in females. The results demonstrated that high CV risk and obesity predispose older adults to gradual loss of brain volume across cortical regions over several decades, occurring in a bell-shaped manner over time. The detrimental impact of CV risk was widespread throughout cortical regions, highlighting how CV risk can impair a range of cognitive functions. 

Prominent effects were identified in temporal lobe structures, regions affected early in Alzheimer’s disease pathogenesis. This highlights the risk of memory impairments and Alzheimer’s disease development in those with greater CV risk.

Several possible mechanistic pathways which may mediate the detrimental impact of CV risk on brain health were postulated. These include increased amyloid-β (main component of senile plaques in patients with Alzheimer’s disease) production associated with increased cholesterol levels, hypertension-induced oxidative stress on cerebrovasculature, and aberrant inflammatory response induced by dysregulated endocrine homeostasis in obesity and disrupted insulin signalling in diabetes.

The authors thus concluded that aggressively addressing CV risk and obesity a decade earlier in males than females may be imperative to achieve a therapeutic benefit in preventing neurodegeneration and cognitive decline.