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.
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.
Entities:
Keywords:
Alzheimer’s disease; atrophy; cognition; familial Alzheimer’s disease; memory; sex
Authors: Clara Vila-Castelar; Pierre N Tariot; Kaycee M Sink; David Clayton; Jessica B Langbaum; Ronald G Thomas; Yinghua Chen; Yi Su; Kewei Chen; Nan Hu; Margarita Giraldo-Chica; Carlos Tobón; Natalia Acosta-Baena; Ernesto Luna; Marisol Londoño; Paula Ospina; Victoria Tirado; Claudia Muñoz; Eliana Henao; Yamile Bocanegra; Sergio Alvarez; Silvia Rios-Romenets; Valentina Ghisays; Dhruman Goradia; Wendy Lee; Ji Luo; Michael H Malek-Ahmadi; Hillary D Protas; Francisco Lopera; Eric M Reiman; Yakeel T Quiroz Journal: Alzheimers Dement Date: 2022-02-01 Impact factor: 16.655
Authors: Joshua T Fox-Fuller; Arabiye Artola; Kewei Chen; Margaret Pulsifer; Dora Ramirez; Natalia Londono; Daniel C Aguirre-Acevedo; Clara Vila-Castelar; Ana Baena; Jairo Martinez; Joseph F Arboleda-Velasquez; Jessica B Langbaum; Pierre N Tariot; Eric M Reiman; Francisco Lopera; Yakeel T Quiroz Journal: JAMA Netw Open Date: 2021-08-02
Authors: Jairo E Martinez; Enmanuelle Pardilla-Delgado; Edmarie Guzmán-Vélez; Clara Vila-Castelar; Rebecca Amariglio; Jennifer Gatchel; Daniel C Aguirre-Acevedo; Yamile Bocanegra; Ana Baena; Eliana Henao; Victoria Tirado; Claudia Muñoz; Margarita Giraldo-Chica; Francisco Lopera; Yakeel T Quiroz Journal: J Int Neuropsychol Soc Date: 2021-06-30 Impact factor: 3.114