Examining Sex Differences in Markers of Cognition and Neurodegeneration in Autosomal Dominant Alzheimer's Disease: Preliminary Findings from the Colombian Alzheimer's Prevention Initiative Biomarker Study

Abstract

Background: Growing evidence suggests that there may be a sex-specific biological risk for Alzheimer's disease (AD). Individuals with autosomal dominant AD due to a mutation (E280A) in Presenilin-1 (PSEN1) are genetically determined to develop early-onset dementia and thus, have few age-related risk factors for AD that are known to vary by sex (i.e., cardiovascular disease, menopause, life expectancy).

Objective: Investigate sex differences in markers of cognition and neurodegeneration in autosomal dominant AD.

Methods: We conducted a retrospective study in 19 cognitively-unimpaired PSEN1 mutation carriers (age range 20-44; 11 females), 11 symptomatic carriers (age range 42-56; 8 females), and 23 matched non-carriers family members (age range 20-50; 13 females). We examined hippocampal volume ratio, CERAD Total Score, and CERAD Word List (i.e., Learning, Delayed Recall, and Recognition). Mann-Whitney U tests, Spearman correlations and regression models were conducted.

Results: There were no differential associations between age, CERAD Total Score, CERAD Word List-Learning, Delayed Recall, Recognition, and hippocampal volume ratio in male and female carriers and non-carriers. Cognitively-unimpaired female carriers showed better CERAD Total scores and CERAD Word List-Learning than cognitively-unimpaired male carriers, despite having similar hippocampal volume ratios. The interaction of sex and hippocampal volume ratio did not predict cognitive performance across groups.

Conclusion: Our preliminary findings suggest that cognitively-unimpaired female carriers showed a verbal memory reserve, and as disease progresses, female carriers did not exhibit a cognitive susceptibility to AD-related neurodegeneration. Future studies with larger samples of autosomal dominant AD are warranted to further understand sex differences in AD-related clinical and pathological markers.

Keywords: Alzheimer’s disease; atrophy; cognition; familial Alzheimer’s disease; memory; sex.

Figure 1.. Relations among age, cognition and neurodegeneration in PSEN1 male and female carriers

Note. A, Verbal memory learning as a function of age. B, Verbal memory delayed recall as a function of age. C, Verbal memory recognition as a function of age. D, CERAD Total score as a function of age. E, Hippocampal volume ratio as a function of age. Green dots represent male PSEN1 mutation carriers and orange triangles represent female PSEN1 mutation carriers.

Figure 2.. Relations among neurodegeneration and cognition in PSEN1 male and female carriers

Note. A, Verbal memory learning as a function of hippocampal volume ratio. B, Verbal memory delayed recall as a function of hippocampal volume ratio. C, Verbal memory recognition as a function of hippocampal volume ratio. D, CERAD Total scores as a function of hippocampal volume ratio. Green dots represent male PSEN1 mutation carriers and orange triangles represent female PSEN1 mutation carriers.