ObjectiveTo automatically extract and quantify specific disease biomarkers of prosody from the acoustic properties of speech in patients with primary progressive aphasia.MethodsWe analyzed speech samples from 59 progressive aphasic patients (non‐fluent/agrammatic = 15, semantic = 21, logopenic = 23; ages 50–85 years) and 31 matched healthy controls (ages 54–89 years). Using a novel, automated speech analysis protocol, we extracted acoustic measurements of prosody, including fundamental frequency and speech and silent pause durations, and compared these between groups. We then examined their relationships with clinical tests, gray matter atrophy, and cerebrospinal fluid analytes.ResultsWe found a narrowed range of fundamental frequency in patients with non‐fluent/agrammatic variant aphasia (mean 3.86 ± 1.15 semitones) compared with healthy controls (6.06 ± 1.95 semitones; P < 0.001) and patients with semantic variant aphasia (6.12 ± 1.77 semitones; P = 0.001). Mean pause rate was significantly increased in the non‐fluent/agrammatic group (mean 61.4 ± 20.8 pauses per minute) and the logopenic group (58.7 ± 16.4 pauses per minute) compared to controls. In an exploratory analysis, narrowed fundamental frequency range was associated with atrophy in the left inferior frontal cortex. Cerebrospinal level of phosphorylated tau was associated with an acoustic classifier combining fundamental frequency range and pause rate (r = 0.58, P = 0.007). Receiver operating characteristic analysis with this combined classifier distinguished non‐fluent/agrammatic speakers from healthy controls (AUC = 0.94) and from semantic variant patients (AUC = 0.86).InterpretationRestricted fundamental frequency range and increased pause rate are characteristic markers of speech in non‐fluent/agrammatic primary progressive aphasia. These can be extracted with automated speech analysis and are associated with left inferior frontal atrophy and cerebrospinal phosphorylated tau level.

Higher antemortem CSF t-tau/Aβ and lower Aβ levels are predictive of increasing cerebral AD and SYN pathology. These biomarkers may identify patients with LBD vulnerable to cortical SYN pathology who may benefit from both SYN and AD-targeted disease-modifying therapies.

Reduced f0 range reflects impaired prosody in bvFTD. This is associated with neuroanatomic networks implicated in language production and social disorders centered in the frontal lobe. These findings support the feasibility of automated speech analysis in frontotemporal dementia and other disorders.