Aug 2026· Journal of Alzheimer's Disease· Vol 113, pp. 693 - 700· 0 citations· 39 references
Medicine
TL;DR
These findings inform further work on SCD outcomes and related biomarkers, as well as preventive studies that target modifiable risk factors for SCD progression.
Abstract
Background Subjective cognitive decline (SCD) is increasingly recognized in some cases as an early clinical stage in the Alzheimer's disease continuum, yet the factors that predict which individuals will progress to objective impairment remain poorly understood. Objective We evaluated risk factor differences and cognitive domain markers associated with progression in participants with subjective cognitive decline (SCD) at baseline from the NYU Alzheimer's Disease Research Center. Methods We included SCD non-decliners (n = 27), who remained stable, and decliners (n = 24), who progressed to mild cognitive impairment or worse, between the second to sixth yearly follow-up visits. Adjusted mixed-effects models examined group differences and associations between demographic, APOE status, psychometric test performance and comorbidities with longitudinal-decline. Results Overall, mean (SD) age was 67.4 (9.2) and total follow-up time was 5.1 (1.8) years. Lower education (14.9 (3.2) versus 17.3 (2.1)), Hispanic ethnicity (50.0% versus 11.0%), and hypercholesterolemia (adjusted odds ratio: 6.67) were risk factors for progression in SCD, p ≤ 0.05, whereas APOE status was not. Notably, SCD decliners were at increased risk for both amnestic and non-amnestic cognitive-decline with psychometric changes in memory, executive, and language domains (p < 0.001 for all). Conclusions These findings inform further work on SCD outcomes and related biomarkers, as well as preventive studies that target modifiable risk factors for SCD progression.
Episodic memory demonstrated the strongest predictive performance among the individual assessment domains evaluated of 24-month progression from MCI to AD, with functional assessment providing substantial complementary value.
The need for standardized diagnostic criteria and integrative models that encompass the clinical, biological, cognitive, and psychosocial domains to enhance the predictive and diagnostic value of SCD in the context of neurodegenerative disease is underscored.
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