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• W2896667926 abstract "Degeneration of cholinergic neurons is one of the earliest changes in Alzheimer's disease (AD), possibly preceding entorhinal cortex atrophy and cognitive decline (Schmitz 2016). Neuropathologic studies in preclinical and clinical AD demonstrate cholinergic basal forebrain atrophy (Grothe 2013) with the degree of atrophy corresponding to the level of cognitive impairment (Grothe 2010) and amyloid burden (Teipel 2014). Mounting evidence supports the parallel relationship of the cholinergic system and cognition in all stages of Alzheimer's disease. We previously demonstrated that disruption of cholinergic neurotransmission with a muscarinic cholinergic antagonist, scopolamine challenge test (SCT), exacerbates Aβ-related cognitive impairment in preclinical AD by unmasking otherwise undetectable cognitive deficits (Snyder 2014, Lim 2015). Here we present longitudinal follow-up analysis after a 27-month interval evaluating progression of cognitive decline and neocortical amyloid burden. Older adults (n = 63, aged 55-75 years) with subjective cognitive decline and 1st degree family history of AD were enrolled. At baseline visit, all subjects completed SCT with one micro-dose scopolamine administration paired with a well-validated cognitive assay, Groton Maze Learning Test (GMLT), along with positron emission tomography (PET) neuroimaging for beta-amyloid (Aβ) using 18F-florbetapir within 6 weeks of baseline. An individual was considered to have failed the SCT if change on the GMLT composite at 5 hours post dose was above 0. Subsequent cognitive testing was completed at 9, 18 and 27 months post-baseline. Repeat Aβ PET imaging was completed at 27 months. After a 27-month delay interval, participants who failed the SCT at baseline (n=28) showed significantly worse results in cognitive testing performance as well as relatively increased Aβ burden compared to those who passed the SCT (n = 30) at baseline. Participants who passed the SCT showed reliable practice effects on the GMLT after a 27-month delay, whereas those who failed the SCT did not. Cognitive response to SCT (Snyder 2014) predicts progression of cognitive decline and neocortical amyloid burden over a 27 month interval in preclinical AD. SCT may be a low cost, clinically useful screening tool to identify individuals at risk of developing clinical AD, supporting earlier interventions and clinical trial referral . Performance on the International Shopping List (ISLT) Delayed Recall Task, by participants who either failed the scopolamine challenge test (SCT) at baseline (N = 28, at end of study) vs. those who passed the SCT at baseline (N = 30, at end of study), modeled over all four study visits. Dark lines indicate group mean scores at each visit, with SE bars provided. Both between- and within-subject variation is represented in each group, by displaying individual subject change over time, with each case yoked to the group baseline mean score." @default.
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• W2896667926 date "2018-07-01" @default.
• W2896667926 modified "2023-10-12" @default.
• W2896667926 title "P1‐132: DISRUPTION OF CHOLINERGIC NEUROTRANSMISSION, WITHIN A COGNITIVE CHALLENGE PARADIGM, PREDICTS Aβ‐RELATED COGNITIVE IMPAIRMENT IN PRECLINICAL ALZHEIMER'S DISEASE AFTER A 27‐MONTH DELAY INTERVAL" @default.
• W2896667926 doi "https://doi.org/10.1016/j.jalz.2018.06.135" @default.
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