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

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.