Observational studyJMIR formative research2026
Remote Identification of APOE-ε4 Carrier Status in Cognitively Normal Adults via Speech Acoustics: Cross-Sectional Observational Study.
Observational study in JMIR formative research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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10 authors.
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Abstract
backgroundApolipoprotein E ε4 (APOE-ε4), the strongest genetic risk factor for late-onset Alzheimer disease (AD), is associated with early neuromotor vulnerability that may precede measurable cognitive decline. Because speech integrates fine neuromotor processes, acoustic analysis could offer a sensitive, noninvasive marker of preclinical effects.
objectiveThis study aims to determine if speech acoustics distinguish cognitively normal APOE-ε4 carriers from noncarriers, and to assess which speech tasks provide optimal classification performance.
methodsIn this cross-sectional observational study, 80 cognitively normal adults aged 41 to 89 years (22 APOE-ε4 carriers and 58 noncarriers) completed sustained phonation, oral diadochokinetic syllable repetition, passage reading, and spontaneous-speech tasks. Speech samples were collected remotely using participants' personal devices and processed to extract 88 acoustic features from the extended Geneva Minimalistic Acoustic Parameter Set. Task-specific random forest classifiers were developed to distinguish APOE-ε4 carriers from noncarriers. A genetic algorithm was used to select informative features, and model performance was evaluated using leave-one-participant-out cross-validation. Performance metrics included balanced accuracy, accuracy, precision, sensitivity, specificity, F
resultsSpontaneous speech produced the strongest classification performance, with balanced accuracy of 0.84, accuracy of 0.89, sensitivity of 0.73, specificity of 0.95, F
conclusionsAutomated analysis of task-specific acoustic speech features, particularly spontaneous speech, internally distinguished cognitively normal APOE-ε4 carriers from noncarriers. These findings support further validation of speech acoustics as a low-burden digital biomarker of preclinical AD risk and suggest that spontaneous-speech tasks may be especially well suited for future remote and longitudinal assessment.
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