Sex differences in story recall decline in preclinical Alzheimer's disease.

Stage II pre-clinical Alzheimer's disease is defined by the presence of increased amyloid-beta evidenced by fluid and/or imaging biomarkers, in the absence of clinical signs and symptoms. Previous research suggests that pre-clinical sex differences exist on measures of story recall, such as the Wechsler memory scale-revised logical memory test total score. However, sex differences on a composite metric of proper names from that test have not been investigated, and the relationships between sex and amyloid positivity on longitudinal logical memory measures are unclear. We examined longitudinal trajectories of total score and proper names by sex (Aim 1), and by the combination of sex and amyloid status (Aim 2). = 457 Wisconsin registry for Alzheimer's prevention participants with PET Pittsburgh compound B-assessed amyloid status (+/-) were included. Linear mixed-effects models were used to examine the interaction between sex and age at visit (the time variable), and sex and amyloid+/- on longitudinal total and proper name scores. Aim 1 analyses showed a main effect such that female participants, on average, scored higher than males on both total and proper name recall. The interaction between sex and age was not statistically significant, indicating that both sexes experienced a similar average rate of annual decline. Aim 2 analyses showed that amyloid positive participants, regardless of sex, showed steeper declines compared to amyloid negative, female participants (reference group). Thus, while female participants generally outperformed males on story recall measures, the impact of amyloid burden on longitudinal story recall trajectories was not significantly more pronounced in females. Results emphasize the need for further exploration into sex-specific cognitive reserve mechanisms in the context of Alzheimer's disease biomarker burden, as well as in the assessment and understanding of cognitive decline trajectories.