A - 21 Sex Differences in Cortical Thickness and Cognition in Individuals with Autosomal Dominant Alzheimer's Disease.

Abstract

Cortical thinning is a marker of neurodegeneration. Individuals with autosomal dominant Alzheimer's disease (ADAD) develop early-onset dementia with virtually 100% certainty. Cortical thickness fluctuates across the ADAD lifespan, from early-life increased thickness to atrophy proximal to clinical onset. Females have higher cortical thickness and better cognition than males as they age. We examined sex differences in cortical thickness and cognitive performance in adults with ADAD. We assessed 85 Presenilin-1 E280A mutation carriers (74 cognitively-unimpaired, 11 mildly-impaired) from the Colombia-Boston Biomarker Study of ADAD. Mean age was 35.7 (SD = 10), education 10.2 (SD = 9), and 55 were female. Global cognition was measured using Mini-Mental State Examination (MMSE), and memory using CERAD Word List Delayed Recall. Participants underwent structural brain MRI. T-tests assessed between-group differences. Pearson correlations examined associations between cortical thickness and cognition. There were no sex differences in cortical thickness or cognitive performance (all ps > =0.05). For carriers, greater cortical thickness was associated with higher MMSE (r = 0.40, p < 0.001) and memory recall scores (r = 0.43, p < 0.01). Female carriers drove this effect, where greater cortical thickness was associated with higher MMSE (r = 0.46, p < 0.001) and memory recall scores (r = 0.47, p < 0.001); these associations were non-significant in male carriers alone. In cognitively-unimpaired female carriers, increased cortical thickness was associated with worse MMSE (r = -0.44, p < 0.001). We found sex differences in the relation between cortical thickness and cognition in ADAD carriers, which may be relevant to the differential vulnerability and progression of ad in females and males. Future work should investigate potential underlying mechanisms contributing to this sex difference.