Brain cholinergic terminal density utilizing [18F]‐fluoroethoxybenzovesamicol PET in adults with Down's syndrome: Relationship to amyloid PET and cognitive performance

• DOI: 10.1002/alz.70134
• Publication Date: 2025-04-07T04:50:20Z
• Authors: Jason K. Russell; Alexander C. Conley; Brian D. Boyd; John Patrick Begn...; Rachel Schlossberg; Allison Stranick; Adam J. Rosenberg; Lealani Mae Y. Ac...; Dann Martin; Yasmeen Neal; Michael S. Rafii; Julie Dumas; Paul A. Newhouse

AbstractBACKGROUNDAdults with Down syndrome (DS) have increased risk of Alzheimer's disease (AD). The cholinergic system declines in AD, underlying many cognitive deficits. We investigated the relationship between amyloid accumulation and cholinergic terminal density in adults with DS compared to amyloid‐matched controls.METHODSA total of 15 non‐demented adults with DS and 15 amyloid‐matched healthy controls were assessed for [18F]‐FEOBV uptake differences and [18F]‐FEOBV uptake relationships with amyloid accumulation and cognitive performance.RESULTSAdults with DS displayed greater [18F]‐FEOBV uptake than controls, with a similar uptake pattern. Amyloid‐associated differences in [18F]‐FEOBV uptake were observed in adults with DS. [18F]‐FEOBV uptake in adults with DS was positively associated with cognition.DISCUSSIONAdults with DS display higher [18F]‐FEOBV uptake than amyloid‐matched controls but relatively lower [18F]‐FEOBV uptake in individuals with elevated amyloid. Thus, the cholinergic system appears to be adversely affected by AD pathology in individuals with DS, which may be relevant to cognitive decline.Highlights Adults with DS display greater cholinergic terminal density in specific ROIs than amyloid‐match controls. Adults with DS exhibit a similar pattern of cholinergic terminal density across the brain. The first association of cholinergic terminal density with AD pathology in non‐demented adults with DS. Adults with DS display a greater cholinergic terminal decline in association with amyloid accumulation than neurotypically developed age‐matched controls. Region‐specific cholinergic terminal density associated with cognitive performance in adults with DS.