Lower semantic fluency scores and a phonemic-over-semantic advantage predict abnormal CSF P-tau 181 levels in Aβ + patients within the Alzheimer’s disease clinical spectrum

Background The present study aimed to determine whether patients with mild cognitive impairment (MCI) and dementia due to Alzheimer’s disease (AD), semantic verbal fluency (SVF), and the semantic-phonemic discrepancy (SPD) could predict abnormal cerebrospinal fluid (CSF) phosphorylated tau (P-tau 181 ) and total tau (T-tau) levels. Methods Phonemic verbal fluency (PVF) and SVF scores of N = 116 Aβ-positive patients with either MCI due to AD ( N = 39) or probable AD dementia (ADD; N = 77) were retrospectively collected. The SPD was computed by subtracting PVF scores from SVF ones (positive and negative values corresponding to a semantic and phonemic advantage, respectively). Patients were cognitively phenotyped via a thorough test battery and profiled according to the amyloidosis/tauopathy/neurodegeneration (ATN) framework via CSF analyses. Two separate sets of logistic regressions were run to predict normal vs. abnormal P-tau 181 and T-tau levels by encompassing as predictors SVF + PVF and SPD and covarying for demographic, disease-related features, and cognitive profile. Results Lower SVF, but not PVF, scores, as well as a greater phonemic advantage (i.e., negative SPD values), predicted abnormal CSF P-tau 181 levels ( p ≤ .01). Moreover, lower SVF scores were selectively predictive of abnormal CSF T-tau levels too ( p = .016), while the SPD was not. Discussion SVF and the SPD are able to predict tauopathy across the AD spectrum , thus supporting their status of valid, and sufficiently specific, cognitive markers of AD.