Cholinergic denervation occurs early in Parkinson disease

Although Parkinson disease (PD) is viewed traditionally as a motor syndrome secondary to nigrostriatal dopaminergic denervation, recent studies emphasize nonmotor features. Nonmotor comorbidity, such as cognitive impairment, can be explained better by multisystem neurodegeneration that extends beyond the loss of dopaminergic nigral neurons.1 Lewy2 first identified the eponymous Lewy body in neurons of the nucleus basalis of Meynert, the source of cholinergic innervation of the cerebral cortex. There is considerable evidence for altered cholinergic neurotransmission in PD. In the Braak et al.3 staging scheme of PD pathology, nigral and basal forebrain pathology occur simultaneously. Loss of cholinergic forebrain neurons in PD postmortem specimens is of similar magnitude or greater than loss found in Alzheimer disease (AD).4 A postmortem study found greater reductions of acetylcholinesterase (AChE) in the frontal cortex of patients with dementia compared to patients without dementia with PD.5 The development of PET technology to measure AChE functional activity offers the opportunity to study cholinergic innervation in vivo at early stages of neurodegenerative disorders. In this issue of Neurology ®, …