Background:
Women experience greater longevity but also a disproportionately higher lifetime risk of Alzheimer's disease (AD), with a female-to-male prevalence ratio of approximately 2:3. Growing evidence indicates sex-specific manifestations; however, identifying the temporal onset of these differential changes remains a major challenge.
Purpose:
This pilot study explored whether sex differences are detectable in global cognitive performance among individuals with Mild Cognitive Impairment (MCI) and whether sex is a stronger predictor of cognitive scores than other demographic and affective factors.
Methods:
28 subjects (50% females; mean age: 71.4 ± 7.7 years; mean education: 10.9 ± 7.1 years) diagnosed with MCI (MMSE 26-28) were recruited from the Alzheimer Psychogeriatric Center in Catania. Cognition was assessed with Montreal Cognitive Assessment (MoCA), and depressive symptoms with Hamilton Depression Rating Scale (HDRS-21). Independent-samples t-tests, Mann-Whitney U tests, and linear regression analyses controlling for education and HDRS-21 were applied.
Results:
Females scored lower than males on MoCA (U = 27.0, p < 0.001) and on specific domains: Naming (U = 62.5, p < 0.05) and Abstraction (U = 52.0, p < 0.05). Females reported higher depressive symptoms (U = 47.5, p < 0.05). Linear regression showed that sex explained 41% of the variance in MoCA (R² = 0.413, p < 0.01), and remained a significant predictor after adjusting for education and HDRS-21, with females scoring on average 3.27 points lower than males (β = -3.268, p < 0.01).
Conclusions:
Persistent disparities across global cognition and specific MoCA domains highlight the need for sex-sensitive assessment and interventions. These findings support Gender Medicine approaches: tailored strategies may improve prevention and management of neurodegenerative diseases. Moreover, there is a need to revisit the factors traditionally used to predict dementia progression and to clarify their role in disease trajectories. Large-scale studies should clarify how sex differences in executive, memory, and visuospatial functions, together with prognostic factors, influence disease progression.