PT  - JOURNAL ARTICLE
AU  - Adolfo M. García
AU  - Ariane E. Welch
AU  - Maria Luisa Mandelli
AU  - Maya L. Henry
AU  - Sladjana Lukic
AU  - María José Torres Prioris
AU  - Jessica Deleon
AU  - Buddhika M. Ratnasiri
AU  - Diego L. Lorca-Puls
AU  - Bruce L. Miller
AU  - William Seeley
AU  - Adam P. Vogel
AU  - Maria Luisa Gorno-Tempini
TI  - Automated Detection of Speech Timing Alterations in Autopsy-Confirmed Nonfluent/Agrammatic Variant Primary Progressive Aphasia
AID  - 10.1212/WNL.0000000000200750
DP  - 2022 Aug 02
TA  - Neurology
PG  - e500--e511
VI  - 99
IP  - 5
4099  - http://n.neurology.org/content/99/5/e500.short
4100  - http://n.neurology.org/content/99/5/e500.full
SO  - Neurology2022 Aug 02; 99
AB  - Background and Objectives Motor speech function, including speech timing, is a key domain for diagnosing nonfluent/agrammatic variant primary progressive aphasia (nfvPPA). Yet, standard assessments use subjective, specialist-dependent evaluations, undermining reliability and scalability. Moreover, few studies have examined relevant anatomo-clinical alterations in patients with pathologically confirmed diagnoses. This study overcomes such caveats using automated speech timing analyses in a unique cohort of autopsy-proven cases.Methods In a cross-sectional study, we administered an overt reading task and quantified articulation rate, mean syllable and pause duration, and syllable and pause duration variability. Neuroanatomical disruptions were assessed using cortical thickness and white matter (WM) atrophy analysis.Results We evaluated 22 persons with nfvPPA (mean age: 67.3 years; 13 female patients) and confirmed underlying 4-repeat tauopathy, 15 persons with semantic variant primary progressive aphasia (svPPA; mean age: 66.5 years; 8 female patients), and 10 healthy controls (HCs; 70 years; 5 female patients). All 5 speech timing measures revealed alterations in persons with nfvPPA relative to both the HC and svPPA groups, controlling for dementia severity. The articulation rate robustly discriminated individuals with nfvPPA from HCs (area under the ROC curve [AUC] = 0.95), outperforming specialist-dependent perceptual measures of dysarthria and apraxia of speech severity. Patients with nfvPPA exhibited structural abnormalities in left precentral and middle frontal as well as bilateral superior frontal regions, including their underlying WM. The articulation rate correlated with atrophy of the left pars opercularis and supplementary/presupplementary motor areas. Secondary analyses showed that, controlling for dementia severity, all measures yielded greater deficits in patients with nfvPPA and corticobasal degeneration (nfvPPA-CBD, n = 12) than in those with progressive supranuclear palsy pathology (nfvPPA-PSP, n = 10). The articulation rate robustly discriminated between individuals in each subgroup (AUC = 0.82). More widespread cortical thinning was observed for the nfvPPA-CBD than the nfvPPA-PSP group across frontal regions.Discussion Automated speech timing analyses can capture specific markers of nfvPPA while potentially discriminating between patients with different tauopathies. Thanks to its objectivity and scalability; this approach could support standard speech assessments.Classification of Evidence This study provides Class III evidence that automated speech analysis can accurately differentiate patients with nonfluent PPA from normal controls and patients with semantic variant PPA.4Rtau=FTLD-4-repeat tauopathy; AUC=area under the ROC curve; BA=Brodmann area; CBD=corticobasal degeneration; CDR=Clinical Dementia Rating; FTLD=frontotemporal lobar degeneration; FWE=family wise error; HCs=healthy controls; MMSE=Mini-Mental State Examination; nfvPPA=nonfluent/agrammatic variant primary progressive aphasia; nfvPPA-CBD=nonfluent/agrammatic primary progressive aphasia with underlying corticobasal degeneration pathology; nfvPPA-PSP=nonfluent/agrammatic parimary progressive aphasia with underlying progressive supranuclear palsy pathology; PMC=primary motor cortex; PPA=primary progressive aphasia; PPAOS=primary progressive apraxia of speech; preSMA=presupplementary motor area; PSP=progressive supranuclear palsy; ROI=region of interest; SMA=supplementary motor area; svPPA=semantic variant primary progressive aphasia; TIV=total intracranial volume; WM=white matter; GM=gray matter; TE=echo time; TR=repetition time