Validated automatic speech biomarkers in primary progressive aphasia.

Objective: To automatically extract and quantify specific disease biomarkers of prosody from the acoustic properties of speech in patients with primary progressive aphasia.

Methods: We 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.

Results: We 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).

Interpretation: Restricted 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.