ImportanceSubjective cognitive decline (SCD) is recognized to be in the Alzheimer disease (AD) cognitive continuum. The SCD Initiative International Working Group recently proposed SCD-plus (SCD+) features that increase risk for future objective cognitive decline but that have not been assessed in a large community-based setting.ObjectiveTo assess SCD risk for mild cognitive impairment (MCI), AD, and all-cause dementia, using SCD+ criteria among cognitively normal adults.Design, Setting, and ParticipantsThe Framingham Heart Study, a community-based prospective cohort study, assessed SCD between 2005 and 2019, with up to 12 years of follow-up. Participants 60 years and older with normal cognition at analytic baseline were included. Cox proportional hazards (CPH) models were adjusted for baseline age, sex, education, APOE ε4 status, and tertiles of AD polygenic risk score (PRS), excluding the APOE region. Data were analyzed from May 2021 to November 2023.ExposureSCD was assessed longitudinally using a single question and considered present if endorsed at the last cognitively normal visit. It was treated as a time-varying variable, beginning at the first of consecutive, cognitively normal visits, including the last, at which it was endorsed.Main Outcomes and MeasuresConsensus-diagnosed MCI, AD, and all-cause dementia.ResultsThis study included 3585 participants (mean [SD] baseline age, 68.0 [7.7] years; 1975 female [55.1%]). A total of 1596 participants (44.5%) had SCD, and 770 (21.5%) were carriers of APOE ε4. APOE ε4 and tertiles of AD PRS status did not significantly differ between the SCD and non-SCD groups. MCI, AD, and all-cause dementia were diagnosed in 236 participants (6.6%), 73 participants (2.0%), and 89 participants (2.5%), respectively, during follow-up. On average, SCD preceded MCI by 4.4 years, AD by 6.8 years, and all-cause dementia by 6.9 years. SCD was significantly associated with survival time to MCI (hazard ratio [HR], 1.57; 95% CI, 1.22-2.03; P <.001), AD (HR, 2.98; 95% CI, 1.89-4.70; P <.001), and all-cause dementia (HR, 2.14; 95% CI, 1.44-3.18; P <.001). After adjustment for APOE and AD PRS, the hazards of SCD were largely unchanged.Conclusions and RelevanceResults of this cohort study suggest that in a community setting, SCD reflecting SCD+ features was associated with an increased risk of future MCI, AD, and all-cause dementia with similar hazards estimated in clinic-based settings. SCD may be an independent risk factor for AD and other dementias beyond the risk incurred by APOE ε4 and AD PRS.

中文翻译：

---

主观认知能力下降 Plus 和纵向评估以及认知障碍的风险


重要性主观认知能力下降 （SCD） 被认为是阿尔茨海默病 （AD） 认知连续体的一部分。SCD 倡议国际工作组最近提出了 SCD-plus （SCD+） 特征，这些特征会增加未来客观认知能力下降的风险，但尚未在基于大型社区的环境中进行评估。目的使用 SCD+ 标准评估认知正常成人轻度认知障碍 （MCI）、AD 和全因痴呆的 SCD 风险。设计、环境和参与者弗雷明汉心脏研究是一项基于社区的前瞻性队列研究，评估了 2005 年至 2019 年间的 SCD，并进行了长达 12 年的随访。纳入了 60 岁及以上在分析基线时认知正常的参与者。根据基线年龄、性别、教育程度、APOE ε4 状态和 AD 多基因风险评分 （PRS） 的三分位数调整了 Cox 比例风险 （CPH） 模型，不包括 APOE 区域。分析了 2021 年 5 月至 2023 年 11 月的数据，使用单个问题纵向评估了 ExposureSCD，如果在最后一次认知正常的就诊时得到认可，则认为存在。它被视为一个随时间变化的变量，从连续的、认知正常的第一次就诊开始，包括最后一次，它被认可。主要结局和测量共识诊断的 MCI、AD 和全因痴呆。结果本研究包括 3585 名参与者 （平均 [SD] 基线年龄，68.0 [7.7] 岁;1975 名女性 [55.1%]）。共有 1596 名参与者 （44.5%） 患有 SCD，其中 770 名 （21.5%） 是 APOE ε4 携带者。APOE ε4 和 AD PRS 状态的三分位数在 SCD 组和非 SCD 组之间没有显著差异。在随访期间，分别有 236 名参与者 （6.6%）、73 名参与者 （2.0%） 和 89 名参与者 （2.5%） 诊断出 MCI、AD 和全因痴呆。 平均而言，SCD 比 MCI 早 4.4 年，AD 早 6.8 年，全因痴呆早 6.9 年。SCD 与 MCI 的生存时间显著相关 （风险比 [HR]，1.57;95% CI，1.22-2.03;P <。001）、AD（HR，2.98;95% CI，1.89-4.70;P <。001） 和全因痴呆 （HR， 2.14;95% CI， 1.44-3.18;P <。001）. 调整 APOE 和 AD PRS 后，SCD 的危害基本没有变化。结论和相关性 该队列研究的结果表明，在社区环境中，反映 SCD+ 特征的 SCD 与未来 MCI、AD 和全因痴呆的风险增加相关，在基于临床的环境中估计了类似的危害。SCD 可能是 AD 和其他痴呆症的独立危险因素，超出了 APOE ε4 和 AD PRS 带来的风险。