Biomarker validation of a decline in semantic processing in preclinical Alzheimer's disease.
OBJECTIVE Differentially worse performance on category versus letter fluency suggests greater semantic versus retrieval difficulties. This discrepancy, combined with reduced episodic memory, has widespread clinical utility in diagnosing Alzheimer's disease (AD) Our objective was to investigate whether changes in semantic processing, as measured by the discrepancy between category and letter fluency, was detectable in preclinical AD: in clinically normal older adults with abnormal b amyloid (Ab) deposition on positron emission tomography (PET) neuroimaging. METHOD Clinically normal older adults (mean Mini Mental State Exam (MMSE) score 29) were classified as Ab+ (n 70) or Ab (n 205) using Pittsburgh Compound B (PET) imaging. Participants completed letter fluency (FAS; word generation to letters F A S) and category fluency (CAT; word generation to animals, vegetables, fruits) annually (mean follow up 2.42 years) The effect of Ab status on fluency over time was examined using linear mixed models controlling for age, sex, and education. To dissociate effects related to semantic (CAT) versus retrieval processes (CAT and FAS) we repeated models predicting CAT over time, controlling for FAS and likewise for CAT controlling for FAS. RESULTS At baseline, the Ab+ group performed better on FAS compared with the Ab group but comparably on CAT. Longitudinally, the Ab+ group demonstrated greater decline on CAT compared with the Ab group (p .0011) This finding remained significant even when covarying for FAS (p .0107) Ab+ participants similarly declined compared with Ab participants on FAS (p .0112) but this effect became insignificant when covarying for CAT (p .1607) CONCLUSION These findings provide biomarker validation for the greater specificity of declines in category versus letter fluency to underlying AD pathology. Our results also suggest that changes in semantic processing occur earlier in the AD trajectory than previously hypothesized. (PsycINFO Database Record
Neuropsychology