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Sex-related differences in the relationship between β-amyloid and cognitive trajectories in older adults.

ABSTRACT: Objective: We aimed to test the hypothesis that elevated neocortical β-amyloid (Aβ), a hallmark feature of Alzheimer's disease (AD), predicts sex-specific cognitive trajectories in clinically normal older adults, with women showing greater risk of decline than men. Method: Florbetapir Aβ positron emission tomography (PET) was acquired in 149 clinically normal older adults (52% female, M_age = 74). Participants underwent cognitive testing at baseline and during annual follow-up visits over a timespan of up to 5.14 years. Mixed-effects regression models evaluated whether relations between baseline neocortical Standardized Uptake Value Ratio (SUVR) and composite scores of episodic memory, executive functioning, and processing speed were moderated by sex (male/female) and apolipoprotein E (APOE) status (ε4 carrier/noncarrier). Results: Higher baseline SUVR was associated with longitudinal decline in episodic memory in women (b = -1.32, p < .001) but not men (b = -0.30, p = .28). Female APOE ε4 carriers with elevated SUVR showed particularly precipitous declines in episodic memory (b = -4.33, p < .001) whereas other cognitive domains were spared. SUVR did not predict changes in executive functioning or processing speed, regardless of sex (ps >.63), though there was a main effect of SUVR on processing speed (b = 2.50, p = .003). Conclusions: Clinically normal women with elevated Aβ are more vulnerable to episodic memory decline than men. Understanding sex-related differences in AD, particularly in preclinical stages, is crucial for guiding precision medicine approaches to early detection and intervention. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

SUBMITTER: Lindbergh CA

PROVIDER: S-EPMC7839841 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe impacts of age and sex on brain structures related to cognitive function may be important for understanding the role of aging in Alzheimer disease for both sexes. We intended to investigate the age and sex differences of cortical morphology in middle-aged and older adults and their relationships with the decline of cognitive function.MethodsIn this cross-sectional study, we examined the cortical morphology in 204 healthy middle-aged and older adult participants aged 45 to 89 years using structural magnetic resonance imaging (sMRI) data from the Dallas Lifespan Brain Study data set. Brain cortical thickness, surface complexity, and gyrification index were analyzed through a completely automated surface-based morphometric analysis using the CAT12 toolbox. Furthermore, we explored the correlation between cortical morphology differences and test scores for processing speed and working memory.ResultsThere were no significant interactions of age and sex with cortical thickness, fractal dimension, or gyrification index. Rather, we found that both males and females showed age-related decreases in cortical thickness, fractal dimension, and gyrification index. There were significant sex differences in the fractal dimension in middle-aged participants and the gyrification index in older adult participants. In addition, there were significant positive correlations between the cortical thickness of the right superior frontal gyrus and Wechsler Adult Intelligence Scale (WAIS)-III Letter-Number Sequencing test scores in males (r=0.394; P<0.001; 95% CI for r values 0.216-0.577) and females (r=0.344; P<0.001; 95% CI for r values 0.197-0.491), respectively. Furthermore, a significant relationship between the gyrification index of the right supramarginal gyrus (SupraMG) and WAIS-III Digit Symbol test scores was observed in older adult participants (r=0.375; P<0.001; 95% CI for r values 0.203-0.522).ConclusionsThe results suggest that, compared with males, females have more extensive differences in cortical morphology. The gyrification index of the right SupraMG can be used as an imaging marker of sexual cognitive differences between males and females in older adults. This study helps to further understand sex differences in the aging of the brain and cognition.

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Sex-related differences in the relationship between β-amyloid and cognitive trajectories in older adults.

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