Risk factors and cognitive domain markers of progression in Subjective Cognitive Decline

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AbstractBackgroundSubjective cognitive decline (SCD) is considered a preclinical stage of Alzheimer’s disease, but drivers and nature of progression remain unclear. We evaluated risk factor differences between SCD decliners and non‐decliners related to demographics, genetics, and presence of comorbidities. We also investigated cognitive domain markers associated with progression over time.MethodA longitudinal analysis was performed on subjects with SCD at baseline from the NYU Alzheimer’s Disease Research Center. We included subjects classified as non‐decliners (n = 27), who remained stable for six annual visits, and decliners (n = 24), who progressed to mild cognitive impairment or worse between the second to sixth follow‐up visits. Generalized linear models examined group differences in demographic and genetic (presence of APOE4 or APOE2 allele) risk factors. Linear and logistic mixed‐effects models with random intercept and slope examined associations of psychometric test performance and comorbidities with longitudinal decline, comparing decliners to non‐decliners. Models included age, sex, education, Hispanic ethnicity, baseline psychometric data, APOE status, and their interactions with time. Time was operationalized as years from baseline for each participant.ResultMean (SD) age was 68.5 (11.3) vs. 66.3 (7.1) years (p = 0.41), and follow‐up time was 3.7 (1.97) vs. 6.3 (1.60) years, (p <0.001) for decliners vs. non‐decliners. Subjects with lower years of education (14.9 (3.2) vs. 17.3 (2.1)) and those of Hispanic ethnicity (52.2% vs. 47.8%) were more likely to be decliners (p ≤ 0.004 for both). There were no differences in APOE2 or APOE4 status between decliners vs. non‐decliners. Decliners were approximately 7 times more likely (aOR: 6.67; 95% CI: 1.30 – 33.33, p = 0.002) to have hypercholesterolemia compared to non‐decliners. SCD decliners were at increased risk for psychometric changes in memory, executive, and language domains (p < 0.001 for all).ConclusionIn this cohort, lower education, Hispanic ethnicity, and hypercholesterolemia are risk factors for progression in SCD, whereas APOE status is not. Although SCD has been primarily defined with regard to concern about memory, SCD decliners are at increased risk for both amnestic and non‐amnestic cognitive decline. This supports further work to relate risk factors to SCD outcomes.