Amyloid pathology is associated with semantic loss in patients with subjective cognitive decline.

Background: Evidence is emerging that subtle language decline is an early indicator of Alzheimer's disease (AD). This study assessed change in semantic and letter fluency in individuals with subjective cognitive decline (SCD), and examined whether trajectories differed between individuals with and without amyloid‐beta (Aβ)‐pathology. Method: Longitudinal data from 437 individuals of the memory clinic‐based Amsterdam Dementia Cohort were included (Age 61±8 years, 184(42%) Female, follow‐up time 5.3±3.7 years; Table 1). Participants were classified as SCD at baseline, had available baseline Aβ‐information and had at least 1 follow‐up on semantic or letter fluency. Baseline Aβ‐status was dichotomized as positive/negative based on local cut‐offs for Aβ1‐42 concentrations in cerebrospinal fluid, or visual inspection of amyloid positron emission tomography‐imaging (Florbetapir or PiB). Two linear mixed models (LMM) were used to investigate change on semantic and letter fluency. Models included time and time*Aβ‐status as predictors of interest, a random intercept for participant, and age, sex, education were adjusted for. LMMs were subsequently stratified for Aβ‐status. Result: At baseline, the groups did not differ in semantic (p = 0.313) or letter fluency (p = 0.294). Over time Aβ‐positive individuals changed more rapidly on semantic fluency compared to Aβ‐negative individuals (β = ‐0.32,CI = ‐0.49 – ‐0.14;p<.001). The Aβ‐positive group declined with 0.35 words per year (CI = ‐0.49 – ‐0.20;p<.001), while Aβ‐negative individuals did not show change (β = 0.03;CI = ‐0.12 – 0.06;p = 0.496) (Figure 1). On letter fluency Aβ‐positive individuals changed differently compared to Aβ‐negative individuals (β = ‐0.38;CI = ‐0.72 – ‐0.04;p = 0.028), to the extent that the Aβ‐positive group did not progress (β = 0.10;CI = ‐0.21 – 0.41;p = 0.533), while Aβ‐negative individuals improved with 0.47 words per year (CI = 0.29 – 0.65;p<.001) (Figure 2). Conclusion: Our results indicate that Aβ‐positive individuals decreased on semantic fluency, but remained stable on letter fluency. In contrast, Aβ‐negative individuals remained stable on semantic fluency, while they improved on letter fluency over time, which might suggest a learning effect. These findings suggest that the presence of Aβ‐pathology is characterized by semantic loss, highlighting the potential of language based performance as a biomarker for Aβ‐pathology in SCD. [ABSTRACT FROM AUTHOR]