This cross-over pilot study aims to study the acceptability of two methods of non-invasive brain stimulation for the treatment of Parkinson's disease mild cognitive impairment (PD-MCI) - repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) targeted at the left dorsolateral prefrontal cortex (DLPFC). Twenty participants will undergo both interventions in a cross-over design. They sequentially undergo four consecutive phases (4 weeks each), 1) no-intervention baseline, 2) rTMS ór tDCS, 3) no-intervention, 4) second intervention. The primary outcome measure will be acceptability of the interventions, and secondary outcomes include feasibility, cognitive function, neuropsychiatric symptoms, motor function. We will use MRI to explore personalized targeting.
RATIONALE: Mild cognitive impairment (MCI) is a highly prevalent non-motor characteristic affecting about 40% of individuals with Parkinson's disease (PD). PD-MCI negatively impacts daily life functioning and quality of life and is associated with presence of other neuropsychiatric symptoms. Importantly, it constitutes a risk factor for later development of PD-related dementia. Despite many endeavours to pharmacologically improve PD-MCI, there is currently no effective treatment. Optimization of dopaminergic therapy in early PD can relieve cognitive deficits, improving cognitive inflexibility and bradyphrenia, but also exacerbating other cognitive domains. Additionally, other non-pharmacological treatment options such as cognitive training have shown moderate effect sizes, but with limited transfer to daily functioning. Non-invasive brain stimulation (NIBS) through repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) has promise in treating PD-MCI. NIBS, particularly institute-based rTMS, is, however, intensive and complex in use, specifically for individuals with motor and cognitive difficulties, which might limit its potential for clinical use. OBJECTIVE: To study the acceptability and feasibility of rTMS and tDCS for the treatment of individuals with PD-MCI. STUDY DESIGN: A cross-over design with three conditions: a baseline condition, rTMS, and tDCS. The study consists of 1) two four-week intervention periods, with rTMS treatment three times a week (total session duration \~40 mins, treatment duration = 20 mins) and tDCS treatment five times a week (total session duration \~30 mins, treatment duration = 20 mins. For the rTMS intervention, stimulation will be performed at the Amsterdam UMC, location VUmc (and thus includes travel time); 2) one 120-minute assessment (baseline) that includes neuropsychological and motor assessment, and MR imaging, and four 60-minute assessments that only includes neuropsychological assessment. STUDY POPULATION: We will enroll twenty individuals with PD-MCI, according to level I criteria by the Movement Disorders Society: Montreal Cognitive Assessment score range \[21-25\], performance 1-2 SD below appropriate norms on at least 2 neuropsychological tests, or recent (\< 6 months) classification of PD-MCI on neuropsychological assessment elsewhere. INTERVENTION: Participants will undergo four consecutive phases in this intervention study: 1) a no-intervention baseline phase, 2) 12 sessions of 20-minute institute-based repetitive transcranial magnetic stimulation (rTMS) (10 Hz) or 20 sessions of 20-minute at-home anodal high-definition transcranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex (DLPFC), 3) a second no-intervention baseline phase, 4) the second alternative NIBS intervention. All phases have a duration of 4 weeks and the order of the NIBS interventions is counterbalanced. MAIN STUDY PARAMETERS: The primary outcome measure will be acceptability of the interventions, and secondary outcomes include feasibility, cognitive function, neuropsychiatric symptoms, motor function. We will use MRI to explore personalized targeting.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
20
High-frequency (10 Hz) rTMS targeting the left DLPFC, based on fMRI-peak activation during performance of the Tower of London task, at 110% resting motor threshold intensity, corrected for scalp-cortex distance at the target location, for a total of 3000 pulses per session, using 30 trains of 10 seconds with 30-second inter-train intervals (total duration: 20 minutes), using neuronavigation to record the pulse location.
Anodal high-definition tDCS. The anode will be placed at the F3 EEG location, coordinates registered using neuronavigation on the first intervention session on-site, and cathodes at Fp1, Fz, C3 and F7, in a ring surrounding the anode, using π cm2 circular stimulation electrodes, stimulating the left DLPFC at 2 mA intensity for a duration of 20 minutes, 15 s ramp up and 15 s ramp down. After an initial on-site instructional tDCS session, the tDCS intervention will be delivered at home, in part remotely-supervised via MS Teams.
Amsterdam UMC
Amsterdam, North Holland, Netherlands
RECRUITINGQuantative acceptability of the interventions (measured seperately)
Measured with Theoretical Framework of Acceptability questionnaire ("TFA-PD questionnaire") score, measuring seven domains of acceptability
Time frame: Eight weeks and sixteen weeks (after first and second intervention)
Qualitative acceptability assessment of both interventions
Qualitative assessment from focus groups after study termination
Time frame: After study termination (i.e., all participants finished)
Intervention compliance (feasibility)
Percent of missed intervention sessions
Time frame: Eight weeks and sixteen weeks (during first and second intervention)
Intervention attrition (feasibility)
Count of dropped out participants
Time frame: After study termination (i.e., all participants finished)
Usability of the tDCS device (feasibility)
System Usability Scale score
Time frame: Eight weeks or sixteen weeks (after tDCS intervention)
Subjective cognitive function
PD-Cognitive Functional Rating Scale score
Time frame: Four, eight, twelve and sixteen weeks
Subjective cognitive function
Cognitive Failures Questionnaire score
Time frame: Four, eight, twelve and sixteen weeks
Global cognitive function
Montreal Cognitive Assessment score
Time frame: Four, eight, twelve and sixteen weeks
Attention/mental processing speed
Trail Making Test A time
Time frame: Four, eight, twelve and sixteen weeks
Executive function
Trail Making Test B time
Time frame: Four, eight, twelve and sixteen weeks
Executive function/language
Letter Fluency score
Time frame: Four, eight, twelve and sixteen weeks
Executive function
Tower of London Accuracy
Time frame: Four, eight, twelve and sixteen weeks
Executive function
Tower of London Reaction Time
Time frame: Four, eight, twelve and sixteen weeks
Episodic Memory
Rey Auditory Verbal Learning Test ("15 Woordentest") Direct Recall score
Time frame: Four, eight, twelve and sixteen weeks
Episodic Memory
Rey Auditory Verbal Learning Test ("15 Woordentest") Delayed Recall score
Time frame: Four, eight, twelve and sixteen weeks
Episodic Memory
Rey Auditory Verbal Learning Test ("15 Woordentest") Recognition score
Time frame: Four, eight, twelve and sixteen weeks
Mental processing speed
Symbol Digit Modalities Test score
Time frame: Four, eight, twelve and sixteen weeks
Verbal attention
Wechsler Adult Intelligence Scale IV-NL-Digit Span Forward
Time frame: Four, eight, twelve and sixteen weeks
Working memory
Wechsler Adult Intelligence Scale IV-NL-Digit Span Backwards/Sorting
Time frame: Four, eight, twelve and sixteen weeks
Depressive symptoms
Beck Depression Inventory-lb score
Time frame: Four, eight, twelve and sixteen weeks
Anxiety symptoms
Parkinson Anxiety Scale score
Time frame: Four, eight, twelve and sixteen weeks
Functional mobility
Timed Get-up and Go test score
Time frame: Four, eight, twelve and sixteen weeks
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