Abstract
Background: Mild cognitive impairment is a common non-motor symptom of Parkinson's disease (PD-MCI) and has minimal treatment options.Objective: In this double-blind, randomized, sham-controlled trial, we assessed the effect of repeated sessions of intermittent theta-burst stimulation over the left dorsolateral prefrontal cortex on cognition and brain connectivity in subjects with PD-MCI.Methods: Forty-one subjects were randomized to receive real (n = 21) or sham stimulation (n = 20). All subjects underwent neuropsychological assessments before, 1 day, and 1 month after stimulation. Subjects also underwent resting-state functional magnetic resonance imaging before and 48 h after stimulation. The primary outcome was the change in the cognitive domain (executive function, attention, memory, language, and visuospatial abilities) z-scores across time.Results: There was an insignificant effect on cognitive domain z-scores across time when comparing real with sham stimulation and correcting for multiple comparisons across cognitive domains (p > 0.05 Bonferroni correction). However, the real stimulation group demonstrated a trend toward improved executive functioning scores at the 1-month follow-up compared with sham (p < 0.05 uncorrected). After real stimulation, the connectivity of the stimulation site showed decreased connectivity to the left caudate head. There was no change in connectivity within or between the stimulation network (a network of cortical regions connected to the stimulation site) and the striatal network. However, higher baseline connectivity between the stimulation network and the striatal network was associated with improved executive function scores at 1 month.Conclusions: These results suggest that intermittent theta-burst stimulation over the dorsolateral prefrontal cortex in subjects with PD-MCI has minimal effect on cognition compared with sham, although there were trends toward improved executive function. This intervention may be more effective in subjects with higher baseline connectivity between the stimulation network and the striatal network. This trial supports further investigation focusing on executive function and incorporating connectivity-based targeting.Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03243214.
Highlights
Parkinson’s disease is a common neurodegenerative disease that frequently results in cognitive impairment and dementia [1, 2]
The second study investigated the effects of intermittent thetaburst stimulation over the left dorsolateral prefrontal cortex (DLPFC) [15]. iTBS is a patterned form of Transcranial magnetic stimulation (TMS) [16] that can be administered in less time than repetitive TMS (rTMS), may facilitate induction of plasticity mechanisms [17], and may have a beneficial effect on executive functions in healthy subjects [9]
Overall, repeated sessions of iTBS over the left DLPFC appears more promising than bilateral rTMS [or single session iTBS [13]]
Summary
Parkinson’s disease is a common neurodegenerative disease that frequently results in cognitive impairment and dementia [1, 2]. Transcranial magnetic stimulation (TMS) can modulate activity and connectivity within neural networks [4,5,6] and has shown promise in improving cognitive abilities in healthy subjects [7,8,9], including in healthy older adults [10], subjects with mild cognitive impairment and Alzheimer’s disease [11], and depressed Parkinson’s disease subjects [12]. Recent work assessing the efficacy of TMS in Parkinson’s disease with mild cognitive impairment (PD-MCI) has shown mixed results. The real stimulation group experienced a significant increase in global cognition, attention, and visuospatial abilities, whereas the sham group experienced an increase in attention alone This improvement in the real group was seen at a follow-up of 1 month. Mild cognitive impairment is a common non-motor symptom of Parkinson’s disease (PD-MCI) and has minimal treatment options
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