# Digital biomarkers in narrative and conversational speech in Frontotemporal Dementia

> **NIH NIH K99** · UNIVERSITY OF PENNSYLVANIA · 2021 · $129,465

## Abstract

Today clinical criteria are the gold standard to identify variants of Frontotemporal Dementia (FTD). Though well
established and useful clinically, these criteria rely on lengthy procedures that are expensive and invasive.
There is urgent need for reliable, objective, and valid measures to screen for likely pathology and monitor
disease longitudinally in disease-modifying treatment trials. While preparing the PI to become an independent
translational researcher, this research program addresses clinical objectives to develop novel, reproducible,
inexpensive, non-invasive, validated biomarkers derived from automated analyses of digitized speech in
patients with Frontotemporal Lobar Degeneration (FTLD) pathology. This program is also designed with the
scientific objectives to enrich neurobiologic models of language with essential but missing speech components
and to improve our pathophysiologic understanding of spreading pathology. In Aim 1 of the K99 mentored
phase, the PI will identify informative digitized acoustic and lexical markers in antemortem speech and relate
these directly to regional pathologic burden in FTLD-Tau and FTLD-TDP, and uniquely study these speech
markers and associated MRI cortical thinning in presymptomatic and symptomatic mutation carriers. In Aim 2,
she will examine acoustic and lexical markers longitudinally in FTLD-Tau and FTLD-TDP and in mutation
carriers. The PI’s preliminary data show that automated algorithms such as automated speech recognition
(ASR) and natural language processing (NLP) tools extract novel digital markers from speech that are
sensitive and specific to FTD phenotypes, are associated with imaging and biofluid markers of underlying
FTLD pathology, and are related directly to regional pathologic burden in cross-sectional and longitudinal
studies of autopsied FTLD-Tau and FTLD-TDP as well as carriers of mutations related to FTLD. During the
R00 independent phase, Aim 3 will discover novel markers in the highly elusive domain of natural
conversational speech, the most common form of human-to-human communication, and relate these to
biomarkers of FTD. The PI will accomplish these aims with the guidance of a world-class mentoring team (Drs.
Murray Grossman, Mark Liberman, James Gee, and David Irwin) who have expertise in computational
linguistics, neuroimaging, and experimental neuropathology. The PI has available a unique database of 1500
digitized speech samples in deeply endophenotyped autopsied cases and mutation carriers. The mentoring
team has a very strong track record of training postdoctoral fellows for independent research careers. A
detailed training plan includes regular one-on-one meetings, seminars, coursework, grant writing, and
responsible conduct of research. The new skills acquired during this period, combined with the PI’s prior
expertise in cognitive neurology and leadership experience as a Major in the military, will ensure a strong
foundation to launch an independent translational res...

## Key facts

- **NIH application ID:** 10284370
- **Project number:** 1K99AG073510-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Naomi Nevler
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $129,465
- **Award type:** 1
- **Project period:** 2021-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10284370

## Citation

> US National Institutes of Health, RePORTER application 10284370, Digital biomarkers in narrative and conversational speech in Frontotemporal Dementia (1K99AG073510-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10284370. Licensed CC0.

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