Meredith R. Wicklund, M.D.

There is evidence that neurodegenerative changes precede clinical symptoms in Alzheimer’s disease by two decades (Villemagne et al, 2013). Early detection is critical for development of interventions to halt, slow, or even reverse these pathological processes. The promise of plasma biomarkers to identify early pathology is growing rapidly (Palmqvist et al, 2020), however it is likely that multiple converging biomarkers will be necessary to identify the earliest pathological changes, as subtle differences from healthy controls may fall within the margin of error for any given single biomarker measure. Here we propose that the evaluation of speech and language for both baseline (cross-sectional) and longitudinal changes (within-participant) may add significant value to early pre-clinical pathological changes in MCI and AD. This is bolstered by emerging evidence of the relationship between language characteristics and amyloid burden (Verfaillie et al, 2019) and the large literature that characterizes language-use differences and deficits across the spectrum of cognitive decline (e.g., Mueller et al, 2018). We propose to add a series of in-clinic language elicitation tasks that allow for automated assessment of relevant speech and language domains and to validate these measures cross-sectionally and longitudinally relevant to neuropsychological, blood, and PET biomarkers.

The purpose of this study is to verify the clinical benefit of monthly doses of aducanumab in slowing cognitive and functional impairment as measured by changes in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score as compared with placebo in participants with early Alzheimer's disease.