Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
Development of language composites for enhanced sensitivity to multiple plasma biomarkers.
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He Deling, Langhough Rebecca E, Van Hulle Carol, Basche Kristin, Jonaitis Erin, Wilson Rachael, Hermann Bruce, Zetterberg Henrik, Johnson Sterling, Mueller Kimberly D
Аннотация
BACKGROUND: While language deficits are among the earliest detectable signs of Alzheimer`s disease (AD), no existing composites integrate connected speech - essential for capturing real-world communication - limiting precise detection and personalized interventions.
METHODS: We analyzed cohort data from 824 non-demented adults and constructed three language composites: a theoretical composite based on expert knowledge, a connected speech-specific composite derived from the theoretical composite, and an empirical language composite optimized for predicting cognitive progression. We compared their longitudinal sensitivity to plasma tau phosphorylated at threonine 217 (p-tau217), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP).
RESULTS: The empirical language composite showed superior and consistent sensitivity (faster decline rate) with all three biomarkers. Proper name recall declined uniquely with increased p-tau217, while animal fluency declined selectively with higher NfL and GFAP.
DISCUSSION: An empirical language composite captures holistic cognitive-communicative decline, while individual measures may imply a biomarker-specific language profile. Our findings support the clinical utility of plasma biomarkers and language-specific composites as sensitive early indicators of disease progression.
HIGHLIGHTS: Empirical language composite had optimal sensitivity to plasma p-tau217, NfL, GFAP. It comprises words/minute, filled pauses, proper name recall, and animal fluency. It offers potential for language-dominant ADRD precise detection and monitoring.
METHODS: We analyzed cohort data from 824 non-demented adults and constructed three language composites: a theoretical composite based on expert knowledge, a connected speech-specific composite derived from the theoretical composite, and an empirical language composite optimized for predicting cognitive progression. We compared their longitudinal sensitivity to plasma tau phosphorylated at threonine 217 (p-tau217), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP).
RESULTS: The empirical language composite showed superior and consistent sensitivity (faster decline rate) with all three biomarkers. Proper name recall declined uniquely with increased p-tau217, while animal fluency declined selectively with higher NfL and GFAP.
DISCUSSION: An empirical language composite captures holistic cognitive-communicative decline, while individual measures may imply a biomarker-specific language profile. Our findings support the clinical utility of plasma biomarkers and language-specific composites as sensitive early indicators of disease progression.
HIGHLIGHTS: Empirical language composite had optimal sensitivity to plasma p-tau217, NfL, GFAP. It comprises words/minute, filled pauses, proper name recall, and animal fluency. It offers potential for language-dominant ADRD precise detection and monitoring.