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When verbal fluency inverts: Temporality of semantic impairment in preclinical Alzheimer’s disease
Author(s) -
Vonk Jet MJ,
Rentería Miguel Arce,
Geerlings Mirjam I.,
Avila Justina F,
Mayeux Richard,
Manly Jennifer J
Publication year - 2021
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.053877
Subject(s) - fluency , verbal fluency test , psychology , dementia , cohort , audiology , medicine , cognitive psychology , disease , cognition , neuropsychology , psychiatry , pathology , mathematics education
Background Worse semantic than letter fluency performance is a clinical marker of Alzheimer’s disease (AD), but the longitudinal course of performance on these tasks in pre‐dementia stages remains undefined. This study investigated how many years before clinical AD the performance on the two verbal fluency tasks starts to diverge, and if this process develops similarly across race/ethnicity groups. Method To estimate the trajectories and inflection point of verbal fluency performance in years prior to AD diagnosis, we performed piece‐wise linear mixed effects models in a diverse sample of 569 individuals (mean age = 78.5) from a community‐based cohort who were cognitively normal at baseline but developed dementia across 10 years of follow‐up (up to 5 visits). Performance was standardized on 569 age, sex/gender, education, and race/ethnicity matched controls who remained cognitively healthy during follow‐up (i.e., robust norms approach). Models were adjusted for recruitment wave and demographic factors. Result AIC model comparison of spline‐fit revealed that prior to AD diagnosis, performance on both fluency tasks started to decline more rapidly 3.6 years before diagnosis (slope within later timeframe: semantic: B=‐1.34 [‐1.52, ‐1.16], p<.001; letter: B=‐.56 [‐.70, ‐.42], p<.001). Point‐in‐time performance on semantic fluency became worse than letter fluency as of approximately 2.8 years before AD diagnosis due to the disproportionally fast decline of semantic fluency. Stratified models showed that the inflection point for Whites was earlier than for Blacks and Hispanics, but that the rate of decline and flip in performance between the two tasks was similar across race/ethnicity. Conclusion These results show how the conventional clinical index of worse semantic than letter fluency develops over time in the years before AD diagnosis. This study highlights the importance of serial neuropsychological assessments in detecting high‐risk individuals by showing that the differential rate of decline in semantic versus letter fluency is a sensitive preclinical AD‐marker, equivalent across race/ethnicity.