Subjective Cognitive Decline (SCD) may be an early indicator of risk for Alzheimer’s disease (AD). Findings regarding sex differences in SCD are inconsistent. Studying sex differences in SCD within cognitively unimpaired individuals with autosomal-dominant AD (ADAD), who will develop dementia, may inform sex-related SCD variations in preclinical AD. We examined sex differences in SCD within cognitively unimpaired mutation carriers from the world’s largest ADAD kindred and sex differences in the relationship between SCD and memory performance.

We included 310 cognitively unimpaired Presenilin-1 (PSEN-1) E280A mutation carriers (51% females) and 1998 noncarrier family members (56% females) in the study. Subjects and their study partners completed SCD questionnaires and the CERAD word list delayed recall test. ANCOVAs were conducted to examine group differences in SCD, sex, and memory performance. In carriers, partial correlations were used to examine associations between SCD and memory performance covarying for education.

Females in both groups had greater self-reported and study partner-reported SCD than males (all p < 0.001). In female mutation carriers, greater self-reported (p = 0.02) and study partner-reported SCD (p < 0.001) were associated with worse verbal memory. In male mutation carriers, greater self-reported (p = 0.03), but not study partner-reported SCD (p = 0.11) was associated with worse verbal memory.

Study partner-reported SCD may be a stronger indicator of memory decline in females versus males in individuals at risk for developing dementia. Future studies with independent samples and preclinical trials should consider sex differences when recruiting based on SCD criteria.

主观认知衰退 (SCD) 可能是阿尔茨海默病 (AD) 风险的早期指标。关于 SCD 性别差异的研究结果不一致。研究认知未受损的常染色体显性遗传性 AD (ADAD) 个体的 SCD 性别差异，这些个体将发展为痴呆症，可能会告知临床前 AD 中与性别相关的 SCD 变异。我们检查了来自世界上最大的 ADAD 亲属的认知未受损突变携带者中 SCD 的性别差异以及 SCD 与记忆表现之间关系的性别差异。

我们在研究中纳入了 310 名认知未受损的 Presenilin-1 (PSEN-1) E280A 突变携带者（51% 为女性）和 1998 名非携带者家庭成员（56% 为女性）。受试者及其研究伙伴完成了 SCD 问卷和 CERAD 单词列表延迟回忆测试。进行 ANCOVA 以检查 SCD、性别和记忆表现方面的组别差异。在运营商中，偏相关用于检查 SCD 与教育记忆性能协变之间的关联。

两组中的女性自我报告和研究伙伴报告的 SCD 均高于男性（所有p < 0.001）。在女性突变携带者中，更多的自我报告 ( p = 0.02) 和研究伙伴报告的 SCD ( p < 0.001) 与较差的语言记忆相关。在男性突变携带者中，更多的自我报告 ( p = 0.03)，而不是研究伙伴报告的 SCD ( p = 0.11) 与较差的语言记忆相关。

研究伙伴报告的 SCD 可能是一个更有力的指标，表明在有患痴呆症风险的个体中，女性与男性相比记忆力下降。未来的独立样本研究和临床前试验应在根据 SCD 标准招募时考虑性别差异。