Key PointsQuestion听
Among cognitively normal adults in the community, what is the risk from subjective cognitive decline (SCD), using SCD-plus (SCD+) criteria and assessed longitudinally, associated with mild cognitive impairment (MCI), Alzheimer disease (AD), and all-cause dementia?
Findings听
In this cohort study using longitudinal data from the Framingham Heart Study including 3585 participants, SCD+ was significantly associated with survival time to MCI, AD, and all-cause dementia. Associations were independent of APOE status and an AD polygenic risk score.
Meaning听
In a community setting, SCD+ was associated with an increased risk of future MCI, AD, and all-cause dementia with similar hazards estimated in clinic-based settings.
Importance听
Subjective 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.
Objective听
To assess SCD risk for mild cognitive impairment (MCI), AD, and all-cause dementia, using SCD+ criteria among cognitively normal adults.
Design, Setting, and Participants听
The 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 蔚4 status, and tertiles of AD polygenic risk score (PRS), excluding the APOE region. Data were analyzed from May 2021 to November 2023.
Exposure听
SCD 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 Measures听
Consensus-diagnosed MCI, AD, and all-cause dementia.
Results听
This 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 蔚4. APOE 蔚4 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],鈥�1.57; 95% CI,鈥�1.22-2.03; P鈥�<.001), AD (HR,鈥�2.98; 95% CI,鈥�1.89-4.70; P鈥�<.001), and all-cause dementia (HR,鈥�2.14; 95% CI,鈥�1.44-3.18; P鈥�<.001). After adjustment for APOE and AD PRS, the hazards of SCD were largely unchanged.
Conclusions and Relevance听
Results 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 蔚4 and AD PRS.