Amyloid-related changes in fluency in patients with subjective cognitive decline

Abstract

INTRODUCTION: We examined semantic and phonemic fluency in individuals with subjective cognitive decline (SCD) in relation to amyloid status and clinical progression. METHODS: A total of 490 individuals with SCD (62 ± 8 years, 42% female, 28% amyloid-positive, 17% clinical progression) completed annual fluency assessments (mean ± SD follow-up 4.3 ± 2.9 years). Associations between fluency trajectories, amyloid status, and clinical progression were examined with linear mixed models and joint models. RESULTS: Amyloid-positive individuals declined faster than amyloid-negative individuals on semantic fluency (B = −0.35, p < 0.001), but not on phonemic fluency (B = −0.06, p = 0.218). An annual decline of one word in semantic and phonemic fluency was associated with 22% (hazard ratio [HR] = 1.22, p < 0.001) and 28% (HR = 1.28, p = 0.004) increased risk of clinical progression. DISCUSSION: Our results indicate that decline in semantic fluency is an early indicator of cognitive deficits in preclinical Alzheimer's disease. Highlights: Abnormal amyloid burden is associated with decline in semantic fluency. Fluency trajectories are associated with an increased risk of clinical progression. More refined measures are needed to detect the earliest language deficits.