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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

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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.

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Data availability

Datasets associated with the present study are available upon reasonable request of interested researchers to the corresponding author at the following link: https://doi.org/10.5281/zenodo.7573630.

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Acknowledgements

The authors are thankful to patients and their caregivers. The authors also thank the healthcare professionals involved in patient care.

Funding

This research is funded by the Italian Ministry of Health (Ricerca Corrente, Project 23C125).

Author information

Author notes

  1. Edoardo Nicolò Aiello and Federico Verde contributed equally to this work; Vincenzo Silani and Barbara Poletti contributed equally as well.

Authors and Affiliations

  1. Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Piazzale Brescia 20, 20149, Milan, Italy

    Edoardo Nicolò Aiello, Federico Verde, Federica Solca, Ilaria Milone, Antonia Ratti, Nicola Ticozzi, Vincenzo Silani & Barbara Poletti

  2. PhD Program in Neuroscience, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy

    Edoardo Nicolò Aiello

  3. Department of Pathophysiology and Transplantation, “Dino Ferrari” Center, Università degli Studi di Milano, Milan, Italy

    Federico Verde, Nicola Ticozzi & Vincenzo Silani

  4. Neurology Residency Program, Università Degli Studi Di Milano, Milan, Italy

    Eleonora Giacopuzzi Grigoli

  5. Department of Laboratory Medicine, Laboratory of Clinical Chemistry, IRCCS Istituto Auxologico Italiano, Milan, Italy

    Antonella Dubini & Erminio Torresani

  6. Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Milan, Italy

    Antonia Ratti

  7. Aldo Ravelli Center for Neurotechnology and Experimental Brain Therapeutics, Department of Health Sciences, International Medical School, University of Milan, Milan, Italy

    Roberta Ferrucci & Alberto Priori

  8. ASST Santi Paolo E Carlo, San Paolo University Hospital, Milan, Italy

    Roberta Ferrucci & Alberto Priori

  9. IRCCS Ca’ Granda Foundation Maggiore Policlinico Hospital, Milan, Italy

    Roberta Ferrucci

Authors
  1. Edoardo Nicolò Aiello
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Corresponding author

Correspondence to Barbara Poletti.

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Ethical approval

The participants provided informed consent. This study was approved by the Ethics Committee of IRCCS Istituto Auxologico Italiano (I.D.: 2021_05_18_04).

Conflict of interest

V.S. received compensation for consulting services and/or speaking activities from AveXis, Cytokinetics, Italfarmaco, Liquidweb S.r.l., and Novartis Pharma AG, receives or has received research supports from the Italian Ministry of Health, AriSLA, and E-Rare Joint Transnational Call. He is in the Editorial Board of Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, European Neurology, American Journal of Neurodegenerative Diseases, Frontiers in Neurology. B.P. received compensation for consulting services and/or speaking activities from Liquidweb S.r.l. She is an Associate Editor for Frontiers in Neuroscience. N.T. received compensation for consulting services from Amylyx Pharmaceuticals and Zambon Biotech SA. He is an Associate Editor for Frontiers in Aging Neuroscience. The other authors declare no competing interests.

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Aiello, E.N., Verde, F., Solca, F. et al. 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 44, 1979–1985 (2023). https://doi.org/10.1007/s10072-023-06643-w

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