Age-Related Changes in the Cholinergic System in Adults with Down Syndrome Assessed Using [¹⁸F]-Fluoroethoxybenzovesamicol Positron Emission Tomography Imaging

Abstract

Adults with Down syndrome are genetically predisposed to developing Alzheimer's disease after the age of 40. The cholinergic system, which is critical for cognitive functioning, is known to decline in Alzheimer's disease and although first investigated in individuals with Down syndrome 40 years ago, remains relatively understudied. Existing studies suggest individuals with Down syndrome have an intact cholinergic system at birth that declines through adulthood alongside the development of Alzheimer's disease pathology. The present study provides the first description of cholinergic terminals in vivo in non-demented adults with Down syndrome utilizing [18F]-fluoroethoxybenzovesamicol PET imaging. In addition, we investigated age-associated decline in cholinergic terminal density. Sixteen non-demented adults with Down syndrome and 20 neurotypically developed individuals were studied, comparing radiotracer uptake groupwise and associations with age utilizing a voxel-based approach. Adults with Down syndrome displayed significantly increased [18F]-fluoroethoxybenzovesamicol uptake in the cerebellum, brainstem, thalamus, and numerous cortical regions compared to age-matched controls. Cholinergic terminal density in numerous cortical regions showed a steeper decline associated with increasing age in adults with Down syndrome than observed in neurotypically developed adults in the age range tested. These data suggest increased cholinergic terminal density in early adulthood in individuals with Down syndrome with a more rapid or earlier age-associated decline than is observed in neurotypically developed individuals.