AbstractBackgroundSubtle changes in connected speech language (CSL) comprising fluency disruptions and limited semantic content are present in preclinical stages of Alzheimer’s disease (AD) and dementia. Our prior research suggests that individuals identified by PET imaging as amyloid‐positive experience more rapid decline of semantic content than those without amyloid. Here we expand our analyses to additional CSL measures sensitive to nascent deficits in communication.MethodStudy participants were enrolled in Wisconsin Alzheimer’s Disease Research Center (n= 103) or the Wisconsin Registry for Alzheimer’s Prevention (n= 223), had available cerebrospinal fluid (CSF) measurements, and 1‐4 CSL samples. CSF biomarkers were measured using the exploratory Roche NeuroToolKit assays, a panel of automated robust prototype immunoassays (Roche Diagnostics International Ltd). Speech samples (N=740) were recorded while describing the “Cookie Theft” picture from the Boston Diagnostic Aphasia Examination. The majority of participants (65%) provided ≥ 2 language samples across biennial visits. Moving average types‐tokens ratio (MATTR), content information unit (CIU) density, CIUs per minute, words per minute, and filled pauses were extracted from speech samples. Linear mixed effects models were used to test moderation of age related changes CSL samples by amyloid status (Aβ42/Aβ40 ≥ .046), where age at study visit is the measure of time. ovariates gender, years of education, and number of CSL visits (i.e., practice effects) were included as fixed effects.ResultBaseline demographics and study variables stratified by amyloid status are shown in Table 1. CSF amyloid status did not moderate longitudinal changes in any of the CSL outcomes (Figure 1). After dropping these non‐significant interactions, amyloid‐positive individuals expressed fewer CIUs total and per minute and slightly more filled pauses (Table 2). We also found a significant decline with age in CSL outcomes MATTR, CIUs per minute, and words per minutes. The pattern of results was unchanged after excluding nineteen individuals with cognitive impairment from analyses.ConclusionWe found that amyloid burden associated with connected speech measures reflecting semantic content and word retrieval. CSL is a ‘digital biomarker’ that shows promise as a measure of language; future work will continue to explore longitudinal relationships between CSL and AD biomarkers.