Leveraging speech and artificial intelligence to screen for early Alzheimer's disease and amyloid beta positivity

Early detection of Alzheimer's disease is required to identify patients suitable for disease-modifying medications and to improve access to non-pharmacological preventative interventions. Prior research shows detectable changes in speech in Alzheimer's dementia and its clinical precursors. The current study assesses whether a fully automated speech-based artificial intelligence system can detect cognitive impairment and amyloid beta positivity, which characterize early stages of Alzheimer's disease. Two hundred participants (age 54-85, mean 70.6; 114 female, 86 male) from sister studies in the UK (NCT04828122) and the USA (NCT04928976), completed the same assessments and were combined in the current analyses. Participants were recruited from prior clinical trials where amyloid beta status (97 amyloid positive, 103 amyloid negative, as established via PET or CSF test) and clinical diagnostic status was known (94 cognitively unimpaired, 106 with mild cognitive impairment or mild Alzheimer's disease). The automatic story recall task was administered during supervised in-person or telemedicine assessments, where participants were asked to recall stories immediately and after a brief delay. An artificial intelligence text-pair evaluation model produced vector-based outputs from the original story text and recorded and transcribed participant recalls, quantifying differences between them. Vector-based representations were fed into logistic regression models, trained with tournament leave-pair-out cross-validation analysis to predict amyloid beta status (primary endpoint), mild cognitive impairment and amyloid beta status in diagnostic subgroups (secondary endpoints). Predictions were assessed by the area under the receiver operating characteristic curve for the test result in comparison with reference standards (diagnostic and amyloid status). Simulation analysis evaluated two potential benefits of speech-based screening: (i) mild cognitive impairment screening in primary care compared with the Mini-Mental State Exam, and (ii) pre-screening prior to PET scanning when identifying an amyloid positive sample. Speech-based screening predicted amyloid beta positivity (area under the curve = 0.77) and mild cognitive impairment or mild Alzheimer's disease (area under the curve = 0.83) in the full sample, and predicted amyloid beta in subsamples (mild cognitive impairment or mild Alzheimer's disease: area under the curve = 0.82; cognitively unimpaired: area under the curve = 0.71). Simulation analyses indicated that in primary care, speech-based screening could modestly improve detection of mild cognitive impairment (+8.5%), while reducing false positives (-59.1%). Furthermore, speech-based amyloid pre-screening was estimated to reduce the number of PET scans required by 35.3% and 35.5% in individuals with mild cognitive impairment and cognitively unimpaired individuals, respectively. Speech-based assessment offers accessible and scalable screening for mild cognitive impairment and amyloid beta positivity.