Low Vitamin B12 and Parkinson Disease: Potential Link to Reduced Cholinergic Transmission and Severity of Disease

Dysfunction of the cholinergic systems in PD is thought to possibly play a contributory role in postural instability and cognitive impairment. [...]modulation of cholinergic transmission could improve balance and cognition in these patients.1 Vitamin B12 is lower in patients with PD compared with controls, and low levels have been associated with peripheral neuropathy, cognitive impairment, and more rapid rate of disease progression in PD.2Although this relationship does not necessarily mean causality, there are several hypothetical mechanisms by which reduced vitamin B12 may lead to reduced availability of choline as a substrate for cholinergic transmission. Supporting in vivo data, pathologic studies of patients with PD have shown that PD fallers have decreased numbers of cholinergic neurons in the PPN when compared with PD nonfallers.12 A significant contributing factor to falls in patients with PD is freezing of gait (FOG)- which is an unpredictable-and sudden inability to start or continue walking despite the desire to walk and is exacerbated with decreased attention or during directional change.13 The pathophysiology of FOG is not completely understood, but cholinergic dysfunction may play a role.8 Recent evidence indicated that it involves dysfunction in cerebellar circuits centered in the vermis.13 Although cholinergic input from the PPN to the medulla and spinal cord are, at present, not considered to be part of the central pattern generator for locomotion, they have an important role in regulating muscle tone during locomotion and possibly contribute to modulating attention during locomotion.8 Further, neocortical cholinergic innervation has shown to be decreased in patients with PD and FOG compared with those who do not have FOG.14 Overall, current data suggest a role for impaired cholinergic transmission as a contributory factor in FOG by impaired control of postural tone during gait, impaired attentional modulation during gait, or both. [...]it is possible that, in CSF, vitamin B12 becomes depleted at a relatively early stage of deficiency that is not yet reflected by total serum B12, resulting in a functional CNS B12 deficiency, while serum B12 remains within a normal laboratory reference range. Results of these studies could guide future clinical trials of highdose vitamin B12 supplementation as a well-tolerated symptomatic adjunctive therapy for posture and gait instability and cognitive impairment in PD. Potential Competing Interests: Dr S