TY - JOUR
T1 - Changes in Digital Speech Measures in Asymptomatic Carriers of Pathogenic Variants Associated with Frontotemporal Degeneration
AU - Nevler, Naomi
AU - Cho, Sunghye
AU - Cousins, Katheryn A.Q.
AU - Ash, Sharon
AU - Olm, Christopher A.
AU - Shellikeri, Sanjana
AU - Agmon, Galit
AU - Gonzalez-Recober, Carmen
AU - Xie, Sharon X.
AU - Barker, Megan S.
AU - Manoochehri, Masood
AU - McMillan, Corey T.
AU - Irwin, David J.
AU - Massimo, Lauren
AU - Dratch, Laynie
AU - Cheran, Gayathri
AU - Huey, Edward D.
AU - Cosentino, Stephanie A.
AU - Van Deerlin, Vivianna M.
AU - Liberman, Mark Y.
AU - Grossman, Murray
N1 - Publisher Copyright:
© American Academy of Neurology.
PY - 2024/1/23
Y1 - 2024/1/23
N2 - Background and ObjectivesClinical trials developing therapeutics for frontotemporal degeneration (FTD) focus on pathogenic variant carriers at preclinical stages. Objective, quantitative clinical assessment tools are needed to track stability and delayed disease onset. Natural speech can serve as an accessible, cost-effective assessment tool. We aimed to identify early changes in the natural speech of FTD pathogenic variant carriers before they become symptomatic.MethodsIn this cohort study, speech samples of picture descriptions were collected longitudinally from healthy participants in observational studies at the University of Pennsylvania and Columbia University between 2007 and 2020. Participants were asymptomatic but at risk for familial FTD. Status as "carrier"or "noncarrier"was based on screening for known pathogenic variants in the participant's family. Thirty previously validated digital speech measures derived from automatic speech processing pipelines were selected a priori based on previous studies in patients with FTD and compared between asymptomatic carriers and noncarriers cross-sectionally and longitudinally.ResultsA total of 105 participants, all asymptomatic, included 41 carriers: 12 men [30%], mean age 43 ± 13 years; education, 16 ± 2 years; MMSE 29 ± 1; and 64 noncarriers: 27 men [42%]; mean age, 48 ± 14 years; education, 15 ± 3 years; MMSE 29 ± 1. We identified 4 speech measures that differed between carriers and noncarriers at baseline: mean speech segment duration (mean difference -0.28 seconds, 95% CI -0.55 to -0.02, p = 0.04); word frequency (mean difference 0.07, 95% CI 0.008-0.14, p = 0.03); word ambiguity (mean difference 0.02, 95% CI 0.0008-0.05, p = 0.04); and interjection count per 100 words (mean difference 0.33, 95% CI 0.07-0.59, p = 0.01). Three speech measures deteriorated over time in carriers only: particle count per 100 words per month (β = -0.02, 95% CI -0.03 to -0.004, p = 0.009); total narrative production time in seconds per month (β = -0.24, 95% CI -0.37 to -0.12, p < 0.001); and total number of words per month (β = -0.48, 95% CI -0.78 to -0.19, p = 0.002) including in 3 carriers who later converted to symptomatic disease.DiscussionUsing automatic processing pipelines, we identified early changes in the natural speech of FTD pathogenic variant carriers in the presymptomatic stage. These findings highlight the potential utility of natural speech as a digital clinical outcome assessment tool in FTD, where objective and quantifiable measures for abnormal behavior and language are lacking.
AB - Background and ObjectivesClinical trials developing therapeutics for frontotemporal degeneration (FTD) focus on pathogenic variant carriers at preclinical stages. Objective, quantitative clinical assessment tools are needed to track stability and delayed disease onset. Natural speech can serve as an accessible, cost-effective assessment tool. We aimed to identify early changes in the natural speech of FTD pathogenic variant carriers before they become symptomatic.MethodsIn this cohort study, speech samples of picture descriptions were collected longitudinally from healthy participants in observational studies at the University of Pennsylvania and Columbia University between 2007 and 2020. Participants were asymptomatic but at risk for familial FTD. Status as "carrier"or "noncarrier"was based on screening for known pathogenic variants in the participant's family. Thirty previously validated digital speech measures derived from automatic speech processing pipelines were selected a priori based on previous studies in patients with FTD and compared between asymptomatic carriers and noncarriers cross-sectionally and longitudinally.ResultsA total of 105 participants, all asymptomatic, included 41 carriers: 12 men [30%], mean age 43 ± 13 years; education, 16 ± 2 years; MMSE 29 ± 1; and 64 noncarriers: 27 men [42%]; mean age, 48 ± 14 years; education, 15 ± 3 years; MMSE 29 ± 1. We identified 4 speech measures that differed between carriers and noncarriers at baseline: mean speech segment duration (mean difference -0.28 seconds, 95% CI -0.55 to -0.02, p = 0.04); word frequency (mean difference 0.07, 95% CI 0.008-0.14, p = 0.03); word ambiguity (mean difference 0.02, 95% CI 0.0008-0.05, p = 0.04); and interjection count per 100 words (mean difference 0.33, 95% CI 0.07-0.59, p = 0.01). Three speech measures deteriorated over time in carriers only: particle count per 100 words per month (β = -0.02, 95% CI -0.03 to -0.004, p = 0.009); total narrative production time in seconds per month (β = -0.24, 95% CI -0.37 to -0.12, p < 0.001); and total number of words per month (β = -0.48, 95% CI -0.78 to -0.19, p = 0.002) including in 3 carriers who later converted to symptomatic disease.DiscussionUsing automatic processing pipelines, we identified early changes in the natural speech of FTD pathogenic variant carriers in the presymptomatic stage. These findings highlight the potential utility of natural speech as a digital clinical outcome assessment tool in FTD, where objective and quantifiable measures for abnormal behavior and language are lacking.
UR - http://www.scopus.com/inward/record.url?scp=85181776675&partnerID=8YFLogxK
U2 - 10.1212/WNL.0000000000207926
DO - 10.1212/WNL.0000000000207926
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C2 - 38165329
AN - SCOPUS:85181776675
SN - 0028-3878
VL - 102
JO - Neurology
JF - Neurology
IS - 2
M1 - e207926
ER -