Automatic classification of AD pathology in FTD phenotypes using natural speech

Sunghye Cho, Christopher A. Olm, Sharon Ash, Sanjana Shellikeri, Galit Agmon, Katheryn A.Q. Cousins, David J. Irwin, Murray Grossman, Mark Liberman, Naomi Nevler

Research output: Contribution to journalArticlepeer-review


INTRODUCTION: Screening for Alzheimer's disease neuropathologic change (ADNC) in individuals with atypical presentations is challenging but essential for clinical management. We trained automatic speech-based classifiers to distinguish frontotemporal dementia (FTD) patients with ADNC from those with frontotemporal lobar degeneration (FTLD). METHODS: We trained automatic classifiers with 99 speech features from 1 minute speech samples of 179 participants (ADNC = 36, FTLD = 60, healthy controls [HC] = 89). Patients’ pathology was assigned based on autopsy or cerebrospinal fluid analytes. Structural network-based magnetic resonance imaging analyses identified anatomical correlates of distinct speech features. RESULTS: Our classifier showed 0.88 (Formula presented.) 0.03 area under the curve (AUC) for ADNC versus FTLD and 0.93 (Formula presented.) 0.04 AUC for patients versus HC. Noun frequency and pause rate correlated with gray matter volume loss in the limbic and salience networks, respectively. DISCUSSION: Brief naturalistic speech samples can be used for screening FTD patients for underlying ADNC in vivo. This work supports the future development of digital assessment tools for FTD. Highlights: We trained machine learning classifiers for frontotemporal dementia patients using natural speech. We grouped participants by neuropathological diagnosis (autopsy) or cerebrospinal fluid biomarkers. Classifiers well distinguished underlying pathology (Alzheimer's disease vs. frontotemporal lobar degeneration) in patients. We identified important features through an explainable artificial intelligence approach. This work lays the groundwork for a speech-based neuropathology screening tool.

Original languageEnglish
Pages (from-to)3416-3428
Number of pages13
JournalAlzheimer's and Dementia
Issue number5
Early online date4 Apr 2024
StatePublished - May 2024
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.


  • Alzheimer's disease
  • automated speech analysis
  • frontotemporal lobar degeneration
  • machine learning classification
  • natural speech
  • pathology


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