TY - JOUR
T1 - Amyloid-related changes in fluency in patients with subjective cognitive decline
AU - van den Berg, Rosanne L.
AU - Butterbrod, Elke
AU - de Boer, Casper
AU - Schlüter, Lisa-Marie
AU - van Harten, Argonde C.
AU - Teunissen, Charlotte E.
AU - van de Giessen, Elsmarieke
AU - van der Flier, Wiesje M.
AU - Sikkes, Sietske A. M.
N1 - Publisher Copyright:
© 2025 The Author(s). Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.
PY - 2025/1/1
Y1 - 2025/1/1
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - amyloid positive
KW - language
KW - longitudinal
KW - subjective cognitive decline
KW - verbal fluency
UR - https://www.scopus.com/pages/publications/85215604999
U2 - 10.1002/dad2.70063
DO - 10.1002/dad2.70063
M3 - Article
C2 - 39822289
SN - 2352-8729
VL - 17
JO - Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
JF - Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
IS - 1
M1 - e70063
ER -