A longitudinal study of brain magnetic resonance imaging scans revealed that men exhibited more widespread age-related decline in cortical thickness, cortical surface area, and subcortical volume as they aged, whereas women showed declines in fewer regions of the brain and greater ventricular expansion. The findings could challenge some of the beliefs surrounding the role of sex in Alzheimer’s disease and encourage alternative avenues of research.
In the study, lead study author Anne Ravndal, of the Center for Lifespan Changes in Brain and Cognition, in the Department of Psychology, at the University of Oslo, and her colleagues analyzed 12,638 longitudinal brain magnetic resonance imaging (MRI) scans from 4,726 cognitively healthy participants aged 17 to 95 years across 14 cohorts. Among the 87 brain indices observed in the study, 20% demonstrated greater declines in men compared with in women: namely, total brain, gray matter, white matter, lobar volumes as well as cuneus, lingual, parahippocampal, pericalcarine cortical thickness. Men also showed steeper reductions in occipital lobe volume, fusiform surface area, and postcentral surface area—the latter losing 0.20% annually in men vs 0.12% in women. Notably, when adjusting for life expectancy and proximity to death with sensitivity analysis, many of the observed sex differences in cortical decline in men attenuated, while insular, medial orbitofrontal, and parahippocampal surface area declines increased in women.
“These findings suggest that the higher prevalence of [Alzheimer's disease] diagnoses in women likely stems from factors beyond differential rates of age-related brain atrophy,” the study authors noted. “This observation calls for investigations of mechanisms beyond structural brain changes to explain women’s higher levels of [Alzheimer’s disease] diagnosis.”
The investigators suggested future investigations into risk and protective factors, gene-environment interactions, diagnostic patterns, and survival biases.
There were several limitations to the study. Most notably, the investigators acknowledged the biological and sociocultural influences that may impact Alzheimer’s disease diagnosis. Their reliance on MRI-based morphometry couldn't capture microstructural, vascular, or molecular processes that may have differed by sex. The study was also limited to cognitively healthy individuals, which may have limited generalizability.
Full disclosures can be found in the study.
Source: PNAS