PD Dementia: Revisiting Deep Brain Stimulation Therapy

A recent editorial published in JAMA Neurology discussed a study proposing deep brain stimulation of the nucleus basalis of Meynert (NBM) as a therapy for Parkinson disease dementia (PDD), which challenges the established idea that DBS is contraindicated in dementia.

Authors Wissam Deeb, MD, and coauthors explain that the most important source of cholinergic innervation to the neocortex is the NBM and that the loss of cholinergic innervation in this region has been shown to be associated with PD complications such as agitation, delusions, and visual hallucinations. With the lack of current effective treatments for PDD, researchers have been challenged to innovate novel therapy models.

Dr Deeb and coauthors discuss the study and findings of the article by Gratwicke et al (2017; doi:10.1001/jamaneurol.2017.3762), which appears in the same JAMA Neurology issue as the editorial—a pilot double-blind, randomized, crossover-design study that evaluated the effects of bilateral intermediate NBM DBS stimulation measured by cognitive, psychiatric, and motor tests.

Six men with PDD (4 of these 6 were severely impaired based on the Mattis dementia rating scale). All 6 patients received stimulation on a fixed frequency of 20 Hz and pulse width of 60 milliseconds. The patients were randomized into

the DBS-on group or the DBS-off group for 6 weeks. This period was followed by a 2-week washout and crossover phase that lasted another 6 weeks.
Dr Deeb and colleagues note that the primary outcome of the study did not demonstrate improved cognition in participants. No significant improvement was seen on battery tests for cognitive function. However, while no participants saw cognitive benefits, all 6 patients enrolled experienced no complications or evidence of short-term cognitive decline; thus, this pilot trial “made the case only for the safety and tolerability of NBM DBS in the setting of PDD” (2017; doi:10.1001/jamaneurol.2017.3798).

Authors feel that it is too premature for the trial findings to overturn the long-established exclusion of PDD and dementia from DBS cohorts, but these results do serve to challenge the existing consensus.—Amanda Del Signore

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