Molecular Imaging of the Cholinergic System in Alzheimer and Lewy Body Dementias: Expanding Views

Purpose of Review Brain cholinergic denervation is a major feature of Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). We reviewed the topography assessed by a cholinergic molecular imaging study in these two major types of dementia. A small meta-analysis directly comparing vesicular acetylcholine transporter (VAChT) PET scans of AD vs. DLB patients is presented. Recent Findings VAChT PET studies showed evidence of extensive cortical cholinergic denervation in both forms of dementia, while multiple subcortical structures were also in DLB. Novel analysis revealed evidence of metathalamic denervation in AD, and epithalamus, premotor/sensorimotor cortical, and striatal losses in DLB. Topographically distinct cortical and subcortical cholinergic lesions can distinguish AD and DLB, and new structures have been highlighted here. Differential vulnerability of specific cholinergic projections is likely associated with specific clinical features of these disorders. Improved understanding of the mechanisms and roles of cholinergic neurotransmission in regions with cholinergic deficits may lead to symptomatic therapies.

Automated summary

This study reviewed brain cholinergic denervation in AD and DLB patients using molecular imaging, revealing distinct cortical and subcortical cholinergic lesions that can differentiate between the two types of dementia. The differential vulnerability of specific cholinergic projections may be associated with specific clinical features of these disorders, offering potential for symptomatic therapies through improved understanding of cholinergic deficits in the brain region.