Deep brain stimulation in Parkinson's dementia

Inclusion criteria: •age 18 years and older; •diagnosis of PD according to the clinical diagnostic criteria of the Movement Disorder Society (MDS) (22) – see Appendix 13.3; •despite optimal pharmacological treatment, at least one of the following symptoms, that are severe enough to impair functioning in daily life independent of dementia: omotor response fluctuations; odyskinesia; opainful dystonia; olevodopa-responsive bradykinesia; •diagnosis of probable or possible PDD according to the MDS clinical diagnostic criteria (6) – see Appendix 13.4 (amongst others this encompasses the development of dementia áfter established diagnosis of PD). This will be based on a standardized neuropsychological examination; i.e. presence of at least 2 abnormal cognitive domains, each consisting of 2 abnormal (i.e., = 2 standard deviations) tests, so at least 4 abnormal tests in total. If a test cannot be executed due to severe cognitive difficulties the test is regarded to be abnormal; •a life expectancy of at least two years; •subject has decision capacity to give informed consent, judgement of which is at the discretion of an experienced neurologist from the study team (see 7.3); •subject provides written informed consent; •regular contact with a caregiver, who has at least approximately twice a week contact with the subject and also provides written informed consent for their own participation. Exclusion criteria: •any neurodegenerative disorder other than PD; •previous neurosurgery for PD (e.g., DBS, pallidotomy, thalamotomy). Nota bene: intrajejunal levodopa infusion or subcutaneous apomorphine infusion are not considered an exclusion criterion; •contraindications for DBS surgery, such as a physical disorder making surgery hazardous; •Hoehn and Yahr stage 4 or 5 at the best moment during the day (23); •co-existence of another abnormality or disorder: othat causes cognitive impairment that may improve with specific treatment; OR othat besides PDD is judged to contribute significantly to the cognitive impairment by the treating physician; •current major depressive episode according to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (24) – see Appendix 13.5; •current psychosis (treatment with antipsychotics is allowed); •other severely disabling condition; •immobility during the greater part of the day not related to off-drug phase (e.g., due to apathy); •pregnancy, breastfeeding, and women of childbearing age not using a reliable method of contraception.