{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T03:31:20Z","timestamp":1790047880130,"version":"4.0.1"},"reference-count":45,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"\n Importance<\/jats:title>\n Primary progressive aphasia (PPA) is defined by relatively isolated speech and language symptoms caused by neurodegeneration of language networks; classification of the different clinical, anatomical, and pathological variants relies on time-intensive, expert-dependent assessments that are not widely available. Scalable, interpretable speech-based tools could support diagnosis and monitoring in clinical care and trials.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To determine whether automated speech analysis of voice recording from a short picture description task can yield clinically interpretable speech and language profiles that (1) distinguish among PPA variants, (2) show variant-specific neuroanatomical correlates, and (3) align with underlying autopsy-confirmed neuropathological diagnoses.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This was a cross-sectional observational study of patients seen between 2001 and 2025 using the participants\u2019 first visit. The setting was a single referral center with external validation in an independent sample from 2 sites. The primary sample included research cohort participants in the following groups: cognitively healthy controls, nonfluent PPA, logopenic PPA, and semantic PPA.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n Picture description task (1-2 minutes of recorded speech) from which 40 linguistic and acoustic features were automatically extracted.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The main outcomes included variant-specific speech profile scores derived from Lasso multinomial logistic regression; classification performance for clinical variants and most common underlying neuropathology; and voxelwise associations between speech-profile scores and gray matter volume.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n A total of 214 participants (mean [SD] age, 65.9 [7.9] years; 118 female [55%]) were included in this analysis (43 in the control group, 50 with nonfluent PPA, 56 with logopenic PPA, and 65 with semantic PPA). Among those with PPA, 64 had postmortem neuropathological data available. Twenty-five features differed between at least 2 PPA variants in 214 patients. Multinomial logistic regression achieved an AUC\u2009of\u20090.90 (95% CI, 0.84-0.97) and generated 3 variant-specific logit scores (speech profiles) using 4 to 8 selected features per variant. External validation in an independent cohort yielded an AUC of 0.90 (95% CI, 0.83-0.97). Profile scores showed associations consistent with established neuroanatomical patterns (n\u2009=\u2009195): left superior and middle frontal and premotor cortex in nonfluent PPA, left posterior temporal cortex and angular gyrus in logopenic PPA, and bilateral (left-predominant) anterior temporal lobes in semantic PPA. In an autopsy-confirmed subset with most common underlying pathology (n\u2009=\u200956), speech profile scores discriminated neuropathology with an AUC\u2009of\u20090.90 (95% CI, 0.80-0.96).<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n Results of this cross-sectional study suggest that automated speech analysis of a short audio sample of connected speech yielded interpretable speech profiles that accurately distinguished PPA clinical, anatomical, and neuropathological subtypes. These automated speech profiles may serve as clinical tools to support differential diagnosis and longitudinal monitoring, particularly in settings where specialized speech-language assessment is limited.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaneurol.2026.2520","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T15:00:46Z","timestamp":1785769246000},"page":"873","source":"Crossref","is-referenced-by-count":1,"title":["Automated Speech Analysis to Identify Clinical, Anatomical, and Pathological Variants of Primary Progressive Aphasia"],"prefix":"10.1001","volume":"83","author":[{"given":"Jet M. J.","family":"Vonk","sequence":"first","affiliation":[{"name":"Edward and Pearl Fein Memory and Aging Center, Department of Neurology, University of California San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giada","family":"Antonicelli","sequence":"additional","affiliation":[{"name":"Edward and Pearl Fein Memory and Aging Center, Department of Neurology, University of California San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddarth","family":"Ramkrishnan","sequence":"additional","affiliation":[{"name":"Edward and Pearl Fein Memory and Aging Center, Department of Neurology, University of California San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Spina","sequence":"additional","affiliation":[{"name":"Edward and Pearl Fein Memory and Aging Center, Department of Neurology, University of California San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howie J.","family":"Rosen","sequence":"additional","affiliation":[{"name":"Edward and Pearl Fein Memory and Aging Center, Department of Neurology, University of California San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William W.","family":"Seeley","sequence":"additional","affiliation":[{"name":"Edward and Pearl Fein Memory and Aging Center, Department of Neurology, University of California San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce L.","family":"Miller","sequence":"additional","affiliation":[{"name":"Edward and Pearl Fein Memory and Aging Center, Department of Neurology, University of California San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya L.","family":"Henry","sequence":"additional","affiliation":[{"name":"Department of Speech, Language, and Hearing Sciences, The University of Texas at Austin, Austin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carly","family":"Millanski","sequence":"additional","affiliation":[{"name":"Department of Speech, Language, and Hearing Sciences, The University of Texas at Austin, Austin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Luisa","family":"Mandelli","sequence":"additional","affiliation":[{"name":"Edward and Pearl Fein Memory and Aging Center, Department of Neurology, University of California San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"Miller","sequence":"additional","affiliation":[{"name":"Edward and Pearl Fein Memory and Aging Center, Department of Neurology, University of California San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Luisa","family":"Gorno-Tempini","sequence":"additional","affiliation":[{"name":"Edward and Pearl Fein Memory and Aging Center, Department of Neurology, University of California San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"4","key":"noi260046r1","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1002\/ana.91","article-title":"Primary progressive aphasia.","volume":"49","author":"Mesulam","year":"2001","journal-title":"Ann Neurol"},{"issue":"11","key":"noi260046r2","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1212\/WNL.0b013e31821103e6","article-title":"Classification of primary progressive aphasia and its variants.","volume":"76","author":"Gorno-Tempini","year":"2011","journal-title":"Neurology"},{"issue":"3","key":"noi260046r3","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1002\/ana.10825","article-title":"Cognition and anatomy in 3 variants of primary progressive aphasia.","volume":"55","author":"Gorno-Tempini","year":"2004","journal-title":"Ann Neurol"},{"key":"noi260046r4","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.21184.1","article-title":"Classification of primary progressive aphasia: challenges and complexities.","volume":"9","author":"Tippett","year":"2020","journal-title":"F1000Res"},{"issue":"3","key":"noi260046r5","doi-asserted-by":"publisher","first-page":"245","DOI":"10.3390\/brainsci15030245","article-title":"Primary progressive aphasias: diagnosis and treatment.","volume":"15","author":"Ortiz","year":"2025","journal-title":"Brain Sci"},{"issue":"2","key":"noi260046r6","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1007\/s00415-023-12030-4","article-title":"Primary progressive aphasia: 6 questions in search of an answer.","volume":"271","author":"Belder","year":"2024","journal-title":"J Neurol"},{"issue":"9","key":"noi260046r7","doi-asserted-by":"publisher","first-page":"3070","DOI":"10.1093\/brain\/awae196","article-title":"Artificial intelligence classifies primary progressive aphasia from connected speech.","volume":"147","author":"Rezaii","year":"2024","journal-title":"Brain"},{"issue":"Pt 7","key":"noi260046r8","doi-asserted-by":"publisher","first-page":"2069","DOI":"10.1093\/brain\/awq129","article-title":"Connected speech production in 3 variants of primary progressive aphasia.","volume":"133","author":"Wilson","year":"2010","journal-title":"Brain"},{"issue":"1","key":"noi260046r9","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1002\/acn3.653","article-title":"Validated automatic speech biomarkers in primary progressive aphasia.","volume":"6","author":"Nevler","year":"2018","journal-title":"Ann Clin Transl Neurol"},{"issue":"5","key":"noi260046r10","doi-asserted-by":"publisher","first-page":"e500","DOI":"10.1212\/WNL.0000000000200750","article-title":"Automated detection of speech timing alterations in autopsy-confirmed nonfluent\/agrammatic variant primary progressive aphasia.","volume":"99","author":"Garc\u00eda","year":"2022","journal-title":"Neurology"},{"key":"noi260046r11","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.cortex.2012.12.006","article-title":"Automated classification of primary progressive aphasia subtypes from narrative speech transcripts.","volume":"55","author":"Fraser","year":"2014","journal-title":"Cortex"},{"key":"noi260046r12","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.cortex.2020.08.027","article-title":"Automated profiling of spontaneous speech in primary progressive aphasia and behavioral-variant frontotemporal dementia: an approach based on usage-frequency.","volume":"133","author":"Zimmerer","year":"2020","journal-title":"Cortex"},{"issue":"3","key":"noi260046r13","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.3233\/JAD-201101","article-title":"Automatic subtyping of individuals with primary progressive aphasia.","volume":"79","author":"Themistocleous","year":"2021","journal-title":"J Alzheimers Dis"},{"issue":"6","key":"noi260046r15","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1212\/WNL.51.6.1546","article-title":"Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria.","volume":"51","author":"Neary","year":"1998","journal-title":"Neurology"},{"issue":"2","key":"noi260046r16","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1007\/s42761-023-00185-2","article-title":"Emotional granularity is associated with daily experiential diversity.","volume":"4","author":"Hoemann","year":"2023","journal-title":"Affect Sci"},{"issue":"9","key":"noi260046r17","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000213556","article-title":"Automated speech analysis to differentiate frontal and right anterior temporal lobe atrophy in frontotemporal dementia.","volume":"104","author":"Vonk","year":"2025","journal-title":"Neurology"},{"key":"noi260046r18","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2020.103658","article-title":"Challenges and solutions to employing natural language processing and machine learning to measure patients\u2019 health literacy and physician writing complexity: the ECLIPPSE study.","volume":"113","author":"Brown","year":"2021","journal-title":"J Biomed Inform"},{"issue":"8","key":"noi260046r19","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1080\/02699206.2020.1827458","article-title":"How many words make a sample\u2014determining the minimum number of word tokens needed in connected speech samples for child speech assessment.","volume":"35","author":"Wren","year":"2021","journal-title":"Clin Linguist Phon"},{"issue":"9596","key":"noi260046r20","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1016\/S0140-6736(07)61602-X","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.","volume":"370","author":"von Elm","year":"2007","journal-title":"Lancet"},{"issue":"3","key":"noi260046r27","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1002\/ana.24885","article-title":"Typical and atypical pathology in primary progressive aphasia variants.","volume":"81","author":"Spinelli","year":"2017","journal-title":"Ann Neurol"},{"issue":"1","key":"noi260046r28","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1007\/s00401-011-0845-8","article-title":"A harmonized classification system for FTLD-TDP pathology.","volume":"122","author":"Mackenzie","year":"2011","journal-title":"Acta Neuropathol"},{"issue":"1","key":"noi260046r29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00401-009-0612-2","article-title":"Nomenclature and nosology for neuropathologic subtypes of frontotemporal lobar degeneration: an update.","volume":"119","author":"Mackenzie","year":"2010","journal-title":"Acta Neuropathol"},{"issue":"2","key":"noi260046r30","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1002\/ana.22424","article-title":"Clinicopathological correlations in corticobasal degeneration.","volume":"70","author":"Lee","year":"2011","journal-title":"Ann Neurol"},{"issue":"1","key":"noi260046r31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00401-011-0910-3","article-title":"National Institute on Aging-Alzheimer\u2019s Association guidelines for the neuropathologic assessment of Alzheimer disease: a practical approach.","volume":"123","author":"Montine","year":"2012","journal-title":"Acta Neuropathol"},{"issue":"29","key":"noi260046r32","doi-asserted-by":"publisher","first-page":"9754","DOI":"10.1523\/JNEUROSCI.3464-13.2014","article-title":"Frontal white matter tracts sustaining speech production in primary progressive aphasia.","volume":"34","author":"Mandelli","year":"2014","journal-title":"J Neurosci"},{"issue":"1","key":"noi260046r33","doi-asserted-by":"publisher","DOI":"10.4061\/2011\/546871","article-title":"Joint assessment of structural, perfusion, and diffusion MRI in Alzheimer disease and frontotemporal dementia.","volume":"2011","author":"Zhang","year":"2011","journal-title":"Int J Alzheimers Dis"},{"issue":"11","key":"noi260046r36","doi-asserted-by":"publisher","first-page":"4390","DOI":"10.1002\/hbm.26388","article-title":"Network anatomy in logopenic variant of primary progressive aphasia.","volume":"44","author":"Mandelli","year":"2023","journal-title":"Hum Brain Mapp"},{"issue":"4","key":"noi260046r39","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1212\/WNL.0b013e31829c5d0e","article-title":"Differentiating primary progressive aphasias in a brief sample of connected speech.","volume":"81","author":"Ash","year":"2013","journal-title":"Neurology"},{"issue":"4","key":"noi260046r40","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.3233\/JAD-180990","article-title":"The role of word properties in performance on fluency tasks in people with primary progressive aphasia.","volume":"68","author":"Rofes","year":"2019","journal-title":"J Alzheimers Dis"},{"issue":"Pt 10","key":"noi260046r41","doi-asserted-by":"publisher","first-page":"2778","DOI":"10.1093\/brain\/aww195","article-title":"Healthy brain connectivity predicts atrophy progression in nonfluent variant of primary progressive aphasia.","volume":"139","author":"Mandelli","year":"2016","journal-title":"Brain"},{"issue":"6","key":"noi260046r42","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/S1474-4422(12)70099-6","article-title":"The nonfluent\/agrammatic variant of primary progressive aphasia.","volume":"11","author":"Grossman","year":"2012","journal-title":"Lancet Neurol"},{"key":"noi260046r43","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2022.101760","article-title":"Characterization of the logopenic variant of primary progressive aphasia: a systematic review and meta-analysis.","volume":"82","author":"Conca","year":"2022","journal-title":"Ageing Res Rev"},{"issue":"2","key":"noi260046r44","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1093\/brain\/aww313","article-title":"Focal temporal pole atrophy and network degeneration in semantic variant primary progressive aphasia.","volume":"140","author":"Collins","year":"2017","journal-title":"Brain"},{"issue":"3","key":"noi260046r45","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0120197","article-title":"The semantic variant of primary progressive aphasia: clinical and neuroimaging evidence in single subjects.","volume":"10","author":"Iaccarino","year":"2015","journal-title":"PLoS One"},{"key":"noi260046r21","volume-title":"Western Aphasia Battery Test Manual","author":"Kertesz","year":"1982"},{"key":"noi260046r26","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.18653\/v1\/D15-1162","volume-title":"Proceedings of the 2015 Conference on Empirical Methods in Natural Language Processing","author":"Honnibal","year":"2015"},{"key":"noi260046r14","doi-asserted-by":"crossref","unstructured":"Merhbene? G, Lecron? F, Fortemps? P, Dickerson? BC, Kurpicz-Briki? M, Rezaii? N. Detecting primary progressive aphasia (PPA) from text: a benchmarking study.? bioRxiv. Preprint posted online February 24, 2025. doi:10.1101\/2025.02.19.639032","DOI":"10.1101\/2025.02.19.639032"},{"key":"noi260046r22","unstructured":"Radford? A, Kim? JW, Xu? T, Brockman? G, McLeavey? C, Sutskever? I. Whisper: robust speech recognition via large-scale weak supervision.? arXiv. Preprint posted online December 6, 2022. doi:10.48550\/arXiv.2212.04356"},{"key":"noi260046r23","doi-asserted-by":"crossref","unstructured":"Clarke? N, Morin? B, Bedetti? C, . Automated transcription in primary progressive aphasia: accuracy and effects on classification.? medRxiv. Preprint posted online February 26, 2026. doi:10.64898\/2026.02.24.26346981?","DOI":"10.64898\/2026.02.24.26346981"},{"key":"noi260046r24","unstructured":"Sabahi? S, Klopp-Tosser? A. MyProsody. Accessed December 1, 2022. https:\/\/github.com\/Shahabks\/myprosody"},{"key":"noi260046r25","doi-asserted-by":"crossref","unstructured":"Eyben? F, W\u00f6llmer? M, Sch\u00fcller? B. OpenSMILE: the Munich versatile and fast open-source audio feature extractor. In: Proceedings of the 18th ACM International Conference on Multimedia; 2010;1459-1462. doi:10.1145\/1873951.1874246","DOI":"10.1145\/1873951.1874246"},{"key":"noi260046r34","unstructured":"Github. Computational Anatomy Toolbox for standardized processing of ENIGMA data. Accessed January 20, 2026. https:\/\/neuro-jena.github.io\/enigma-cat12\/"},{"key":"noi260046r35","unstructured":"University College London. SPM12. Accessed January 20, 2026. https:\/\/www.fil.ion.ucl.ac.uk\/spm\/software\/spm12\/"},{"key":"noi260046r37","unstructured":"Github. Jet M.J. Vonk repository overview. Accessed May 6, 2026. https:\/\/github.com\/jmjvonk"},{"key":"noi260046r38","doi-asserted-by":"crossref","unstructured":"Vonk? JM, Lian? J, Cho? CJ, . AI-based speech error detection to differentiate primary progressive aphasia variants.? medRxiv. Preprint posted online February 24, 2026. doi:10.64898\/2026.02.23.26346899?","DOI":"10.64898\/2026.02.23.26346899"}],"container-title":["JAMA Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamaneurology\/articlepdf\/2852243\/jamaneurology_vonk_2026_oi_260046_1789661217.0416.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:00:21Z","timestamp":1790002821000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamaneurology\/fullarticle\/2852243"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,1]]},"references-count":45,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamaneurol.2026.2520","relation":{},"ISSN":["2168-6149"],"issn-type":[{"value":"2168-6149","type":"print"}],"subject":[],"published":{"date-parts":[[2026,9,1]]}}}