Sex differences in cognitive performance in Alzheimer's disease: Insights from the ADAS-Cog-13

BackgroundSex differences in Alzheimer's disease (AD) are well recognized, yet their implications for cognitive assessment remain unclear. Females often demonstrate better cognitive performance than males despite comparable levels of neurodegeneration, which may delay diagnosis.ObjectiveTo evaluate sex differences in cognitive performance across AD continuum.MethodsUsing data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we examined sex differences in total and item-level performance on the 13-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog-13) among cognitively normal (CN) individuals and patients with AD. Regression models were performed, adjusting for hippocampal parenchymal fraction, age, and education.ResultsThe study included 656 CN participants (59% female) and 193 AD patients (45% female). Among CN individuals, female sex was associated with lower total ADAS-Cog-13 scores (β = -2.09, p < 0.0001). CN females demonstrated superior performance on multiple verbal subdomains, including word recall, delayed word recall, naming, and word recognition. In contrast, no significant sex difference was observed in total ADAS-Cog-13 scores among AD patients, although males performed better than females on delayed word recall. Across both groups, greater hippocampal integrity was strongly associated with better global and domain-specific cognitive performance.ConclusionsSex differences in ADAS-Cog-13 performance are evident in cognitively normal individuals but largely attenuated in AD patients. Superior verbal performance in CN females, independent of hippocampal integrity, may mask early cognitive decline and contribute to delayed diagnosis. These findings highlight the importance of accounting for sex when interpreting cognitive test results, particularly in preclinical stages of AD.