RESUMEN
BACKGROUND AND OBJECTIVES: We compared digital speech and language features of patients with amnestic Alzheimer's 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. METHODS: We included patients with aAD or lvPPA with cerebrospinal fluid (CSF) (phosphorylated Tau (p-Tau)/Aß≥ 0.09 and total Tau/Aß≥ 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. RESULTS: We examined patients with aAD (n=44; 62±8 years; 24 females; Mini-Mental State Exam (MMSE)=21.1±4.8) or lvPPA (n=21; 64.1±8.2 years; 11 females; MMSE=23.0±4.2), and healthy controls (HC) (n=28; 65.9±5.9 years, 15 females; MMSE=29±1). Patients with lvPPA produced fewer verbs (10.5±2.3; p=0.001), 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 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: ß=-1.6, p=0.009, BNT: ß=-4.36, p<0.001), adverbs (MMSE: ß=-1.9, p=0.003, BNT: ß=-2.41, p=0.041), pause rate (MMSE: ß=-1.21, p=0.041, BNT: ß=-2.09, p=0.041), and word length (MMSE: ß=1.75, p=0.001, BNT: ß=2.94, p=0.003) were significantly correlated with both MMSE and BNT, but other measures were not correlated with MMSE and/or BNT. 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. DISCUSSION: Our measures captured language and speech differences between the two 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.