Sex differences in brain volume and atrophy observed in biomarker-positive Alzheimer's cohorts

An observational study in Alzheimer's & Dementia examined sex differences in brain structure, pathology, and disease progression among Alzheimer's disease biomarker–positive participants. Multimodal analyses included Alzheimer's Disease Neuroimaging Initiative participants with mild cognitive impairment (MCI; n = 593) or Alzheimer's dementia (n = 270), and National Alzheimer's Coordinating Center participants with MCI (n = 436) or dementia (n = 174). Researchers compared baseline gray matter volume and assessed longitudinal atrophy and conversion from MCI to dementia.

Females with MCI had greater baseline gray matter volume than males, primarily in the thalamus, caudate, cerebellum, postcentral gyrus, and middle cingulate gyrus. These differences were absent at the dementia stage. In ADNI analyses, females had higher baseline cerebrospinal fluid growth-associated protein 43 and greater temporal and parietal tau burden. Females also showed faster annual hippocampal atrophy, although conversion rates to dementia were similar between sexes.

The authors suggest that females may tolerate greater pathology early in disease but experience faster neurodegeneration later. The findings support further evaluation of sex-informed biomarkers rather than demonstrating a difference in dementia conversion risk. The supplied abstract provides no effect sizes, confidence intervals, or adjustment details, limiting assessment of the magnitude and clinical applicability of these observational associations.