Key result
Adults with Down syndrome display higher brain [18F]-FEOBV uptake but steeper age-associated decline versus controls.
Why the study?
The cholinergic system is known to decline in Alzheimer's disease but remains relatively understudied in adults with Down syndrome, who are genetically predisposed to Alzheimer's disease.
Does [18F]-fluoroethoxybenzovesamicol PET imaging show differences in cholinergic terminal density and age-related decline in non-demented adults with Down syndrome compared to neurotypical controls?
Cross-Sectional (n=36)
Yes
Does [18F]-fluoroethoxybenzovesamicol PET imaging show differences in cholinergic terminal density and age-related decline in non-demented adults with Down syndrome compared to neurotypical controls?
p-value: p=<0.001
In vivo PET imaging reveals that non-demented adults with Down syndrome have increased cholinergic terminal density in early adulthood but experience a more rapid age-associated decline compared to neurotypical individuals.
Cholinergic PET patterns in non-demented Down syndrome may signal early vulnerability; leaves open dementia risk links and need for longitudinal data.
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 [ 18 F]-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 [ 18 F]-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.
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Russell et al. (2024) conducted a cross-sectional in Down syndrome (n=36). Down syndrome vs. Neurotypically developed controls was evaluated on Regional [18F]-FEOBV uptake (cholinergic terminal density) (p=<0.001). Adults with Down syndrome displayed significantly increased [18F]-FEOBV uptake in multiple brain regions compared to age-matched controls, but showed a steeper age-associated decline.
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