Association of objective subtle cognitive difficulties with amyloid-β and tau deposition compared to subjective cognitive decline

Purpose: This study evaluated the differences in amyloid-β (Aβ), tau deposition, and longitudinal tau deposition between subjective cognitive decline (SCD) and objective subtle cognitive difficulties (Obj-SCD).

Methods: Participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort (n = 234) and the Huashan cohort (n = 267) included individuals with Obj-SCD, SCD, subjective memory concern (SMC), and healthy controls (HC). General linear models (GLM) were used to compare baseline and longitudinal differences in Aβ and tau among the groups, and to examine the associations between these biomarkers.

Results: Obj-SCD participants had significantly higher Aβ and tau levels compared to HC, with increased annual accumulation of Aβ and tau, especially in Braak stages III-IV. In contrast, SCD/SMC participants did not show significant differences from HC in annual Aβ and tau changes. Baseline Aβ PET correlated with annual tau PET changes in Obj-SCD (Braak III-VI) and SCD/SMC (all Braak stages), and baseline Aβ levels strongly predicted early memory decline in both Obj-SCD and SCD/SMC groups.

Conclusion: This study indicates that Obj-SCD is more strongly associated with Aβ and tau biomarkers, with Aβ contributing to the progression of tau pathology and memory decline. Further research should include more longitudinal data to more robustly validate these findings and clarify the temporal relationship between Aβ and tau in preclinical Alzheimer's disease.