Word Generation from Letter and Semantic Categories Across the Alzheimer’s Disease Spectrum

Background Individuals with mild dementia or mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) often have verbal fluency deficits with greater impairment in generating exemplars from a semantic category (e.g., “animals”) than words that begin with a particular letter (e.g., ‘F’). This may reflect early development of pathology in cortical regions mediating semantic knowledge/organization required to efficiently generate words from a conceptually‐related set of exemplars. We sought to determine if this word generation deficit and discrepancy between category and letter fluency emerges in the preclinical stage of AD. Participants and Methods Semantic and letter fluency tasks were completed by 394 participants. Correct words generated in one minute from each category was summed across animals, fruits, and vegetables (AFV), and across letters ‘F’, ‘A’, and ‘S’ (FAS). CSF was obtained within one year of the fluency tasks and levels of Aβ40, Aβ42, phosphorylated tau (p‐tau), and total tau were measured. Participants were classified as cognitively normal (CN) with negative AD biomarker (CN‐Neg; n = 179), CN with positive AD biomarker (tau/Aβ42 ratio>.609) (CN‐Pos; n = 59), MCI (all biomarker positive; n = 46), and AD dementia (all biomarker positive; n = 110). Results A Group X Task repeated measures ANOVA (adjusting for age and education) showed participants generated more correct words for AFV than FAS (F(1,380) = 20.44; p.001), there was a general stepwise decline in words generated across the AD spectrum (AD