Nucleus Basalis Deep Brain Stimulation for Thinking & Memory Problems in Parkinson's.

Study Overview
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Brief Summary
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We will perform a pilot study to evaluate the effectiveness of human NBM DBS at improving cognitive deficits in PD patients referred and eligible for conventional DBS treatment for coexisting motor impairments. Six patients with PD with both motor fluctuations and cognitive impairments (including but not restricted to deficits in attention and working memory) will have bilateral electrodes implanted to ensure that superficial contacts lie in the conventional motor GPi target, while the deepest electrical contacts lie in the NBM- (see figure 1). We will place electrodes using our conventional image guided, stereotactic frame-based procedure currently used in patients at NHNN. Patients will be randomised into 2 groups in a crossover trial design to have 3 month periods of NBM stimulation switched on or switched off separated by a 1 month washout period, following which the patient will cross over to have the opposite condition for a further 3 months- see timeline. At the end of the crossover period, all patients will be invited for continued follow up with stimulation switched on and will have neuropsychological evaluations at 6 monthly intervals. Patients will be given the option of receiving additional conventional stimulation to the motor GPi, through the higher contacts of each electrode, at the end of the crossover period.

Official Title
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Double Blind, Randomised, Single Centre, Crossover Pilot Trial of Bilateral Nucleus Basalis of Meynert Deep Brain Stimulation to Improve Cognitive Deficits in Patients With Parkinson's Disease.

Conditions
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Dementia in Parkinson's Disease

Intervention / Treatment
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* Device: NBM DBS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients will meet Queen Square brain bank criteria for the diagnosis of PD and will have motor fluctuations (off periods and/or L-dopa induced dyskinesias) in response to medications that are known to improve with GPi DBS, and will be appropriate candidates for GPi DBS aside from the coexistence of cognitive impairment. Patients will be aged between 35 and 80 years. Patients will be able to give informed consent. Patients will meet criteria for PD dementia. Patients will have a MMSE score between 26 and lower cutoff of 21 to restrict the sample to those with mild dementia and cognitive impairment. This will be equivalent to an age and education adjusted scaled score of greater than 5 and lower than 9 (mildly impaired range) on the Mattis Dementia Rating Scale-2. Patients will have only minimal atrophy on pre-operative brain MRI scans. Patients will be living at home and will have a carer living with them e.g. their spouse Able to comply with trial protocol and willing to attend clinic necessary visits Exclusion Criteria: Diagnosis or suspicion of other cause for parkinsonism or dementia. Known abnormality on CT or MRI brain imaging considered likely to compromise compliance with trial protocol. Prior intra-cerebral surgical intervention for Parkinson's disease including Deep Brain stimulation, lesional surgery, growth factor administration, gene therapy or cell transplant.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: NBM DBS Off<br>NBM DBS switched off | Device: NBM DBS<br>* Deep Brain Stimulation targeting the Nucleus Basalis of Meynert<br>|
| Active Comparator: NBM DBS On<br>NBM DBS Switched On | Device: NBM DBS<br>* Deep Brain Stimulation targeting the Nucleus Basalis of Meynert<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Abbreviated cognitive battery | Differences between each item of the abbreviated cognitive battery scores between patients after 3 months ON stimulation and 3 months OFF stimulation. CVLT-II,Verbal Fluency,Simple & Choice RT (CANTAB),Digit span,Posner's covert attention test | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Minimental State Examination |  | 6 months | 
| DRS-2 | Dementia Rating Scale-2 | 6 months | 
| SRM (Faces) | Short Recognition Memory for faces | 6 months | 
| WAIS-III (Letter number sequencing, Arithmetic) | Wechsler Abbreviated Scale of Intelligence | 6 months | 
| FAST | Florida Apraxia Screening test | 6 months | 
| NPI | Neuropsychiatric Inventory | 6 months | 
| BDS | Blessed Dementia Scale | 6 months | 
| HAM-D | Hamilton Depression scale | 6 months | 
| MDS UPDRS | Movement Disorders Society - Unified Parkinson's disease Rating scale | 6 months | 
| PDQ39 | Parkinson's disease quality of life questionnaire | 6 months | 
| GFQ | Gait and falls questioannaire | 6 months | 
| NMS Quest | Non Motor Symptoms Questionnaire | 6 months |