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

Article type: Research Article

Authors: Vila-Castelar, Clara^a | Guzmán-Vélez, Edmarie^a | Pardilla-Delgado, Enmanuelle^a | Buckley, Rachel F.^b | Bocanegra, Yamile^c | Baena, Ana^c | Fox-Fuller, Joshua T.^{a; d} | Tirado, Victoria^c | Muñoz, Claudia^c | Giraldo, Margarita^c | Acosta-Baena, Natalia^c | Rios-Romenets, Silvia^c | Langbaum, Jessica B.^e | Tariot, Pierre N.^e | Lopera, Francisco^c | Reiman, Eric M.^e | Quiroz, Yakeel T.^{a; b; c; *}

Affiliations: [a] Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA | [b] Department of Neurology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA | [c] Grupo de Neurociencias de Antioquia, Universidad de Antioquia, Medellín, Colombia | [d] Department of Psychological & Brain Sciences, Boston University, Boston, MA, USA | [e] Banner Alzheimer’s Institute, Phoenix, AZ, USA

Correspondence: [*] Correspondence to: Yakeel T. Quiroz, Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA. E-mail: [email protected].

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

DOI: 10.3233/JAD-200723

Journal: Journal of Alzheimer's Disease, vol. 77, no. 4, pp. 1743-1753, 2020