Background and ObjectivesWe compared digital speech and language features of patients with amnestic Alzheimer disease (aAD) or logopenic variant primary progressive aphasia (lvPPA) in a biologically confirmed cohort and related these features to neuropsychiatric test scores and CSF analytes.MethodsWe included patients with aAD or lvPPA with CSF (phosphorylated tau ([p-tau]/β-amyloid [Aβ] ≥0.09, and total tau/Aβ ≥0.34) or autopsy confirmation of AD pathology and age-matched healthy controls (HC) recruited at the Frontotemporal Degeneration Center of the University of Pennsylvania for a cross-sectional study. We extracted speech and language variables with automated lexical and acoustic pipelines from participants' oral picture descriptions. We compared the groups and correlated distinct features with clinical ratings and CSF p-tau levels.ResultsWe examined patients with aAD (n = 44; age 62 ± 8 years; 24 women; Mini-Mental State Examination [MMSE] score 21.1 ± 4.8) or lvPPA (n = 21; age 64.1 ± 8.2 years; 11 women; MMSE score 23.0 ± 4.2) and HC (n = 28; age 65.9 ± 5.9 years, 15 women; MMSE score 29 ± 1). Patients with lvPPA produced fewer verbs (10.5 ± 2.3; p = 0.001) and adjectives (2.7 ± 1.3, p = 0.019) and more fillers (7.4 ± 3.9; p = 0.022) with lower lexical diversity (0.84 ± 0.1; p = 0.05) and higher pause rate (54.2 ± 19.2; p = 0.015) than individuals with aAD (verbs 12.5 ± 2; adjectives 3.8 ± 2; fillers 4.9 ± 4.5; lexical diversity 0.87 ± 0.1; pause rate 45.3 ± 12.8). Both groups showed some shared language impairments compared with HC. Word frequency (MMSE score: β = −1.6, p = 0.009; Boston Naming Test [BNT] score: β = −4.36, p < 0.001), adverbs (MMSE score: β = −1.9, p = 0.003; BNT score: β = −2.41, p = 0.041), pause rate (MMSE score: β = −1.21, p = 0.041; BNT score: β = −2.09, p = 0.041), and word length (MMSE score: β = 1.75, p = 0.001; BNT score: β = 2.94, p = 0.003) were significantly correlated with both MMSE and BNT scores, but other measures were not correlated with MMSE and/or BNT score. Prepositions (r = −0.36, p = 0.019), nouns (r = −0.31, p = 0.047), speech segment duration (r = −0.33, p = 0.032), word frequency (r = 0.33, p = 0.036), and pause rate (r = 0.34, p = 0.026) were correlated with patients' CSF p-tau levels.DiscussionOur measures captured language and speech differences between the 2 phenotypes that traditional language-based clinical assessments failed to identify. This work demonstrates the potential of natural speech in reflecting underlying variants with AD pathology.