Lower semantic fluency scores and a phonemic-over-semantic advantage predict abnormal CSF P-tau181 levels in Aβ + patients within the Alzheimer's disease clinical spectrum

Neurol Sci. 2023 Jun;44(6):1979-1985. doi: 10.1007/s10072-023-06643-w. Epub 2023 Jan 27.

Abstract

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-tau181) 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-tau181 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-tau181 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.

Keywords: Alzheimer’s disease; Cerebrospinal fluid; Mild cognitive impairment; Semantic; Tau; Verbal fluency.

MeSH terms

  • Alzheimer Disease* / psychology
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Biomarkers / cerebrospinal fluid
  • Cognitive Dysfunction* / cerebrospinal fluid
  • Cognitive Dysfunction* / diagnosis
  • Humans
  • Retrospective Studies
  • Semantics
  • tau Proteins / cerebrospinal fluid

Substances

  • tau Proteins
  • Biomarkers
  • Amyloid beta-Peptides