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The following is a summary of “Sex-Dependent Effects of Cardiometabolic Health and APOE4 on Brain Age,” published in the August 2024 issue of Neurology by Subramaniapillai et al.

The aging population is increasing rapidly, bringing higher risks of obesity and high blood pressure (BP). These cardiometabolic risk factors (CMRs) show notable sex differences, but their effects on brain health in males and females have not been well studied.

Researchers conducted a retrospective study analyzing how BP and body mass index (BMI) affect brain age differently in men and women and tested how these effects interact with APOE ε4 genotype, a known Alzheimer’s risk factor.

They used MRI data from 2 U.K.-based longitudinal birth cohorts, the Lothian Birth Cohort (1936) and Insight 46 (1947), to study sex differences in how BMI and BP affect brain age. BrainageR 2.1 was used to estimate brain age and linear mixed-effects models to analyze the data, including APOE4 status (i.e., carrier vs. noncarrier). 

The results showed 1,120 participants (48% female) with an average age (SD) of 73(0.72) years for Lothian and 71(0.68) years for insight 46 and about 30% were APOE4 carriers. Higher BP was only linked to older brain age in females (β = 0.43–0.56, P< 0.05). For males, higher BMI was associated with older brain age across time and APOE4 status (β = 0.72–0.77, P< 0.05). In females, higher BMI led to older brain age in APOE4 noncarriers (β = 0.68–0.99, P< 0.05) but younger brain age in carriers, especially at the last time point (β = -1.75, P< 0.05).

Investigators concluded that CMRs, APOE4 status, and brain age relationships varied by sex and time, emphasizing the need for sex-specific analyses to understand aging patterns better and create tailored preventive strategies.

Source: neurology.org/doi/10.1212/WNL.0000000000209744