The Cholinergic ResponsE in Early lewy body Disease (CREED) Study
Dementia, Lewy body disease
Briefly, after providing informed consent, participants will complete: 1. A screening assessment - determines suitability to be included in the study. Participants with possible cognitive impairment due to Lewy body dementia or Parkinson's Disease but do not have a cognitive test as part of clinical practice will be assessed with Montreal Cognitive Assessment (MoCA). The MoCA is an interview (paper and pen test) that will take approximately 10 minutes and will be conducted while the participants attend their usual NHS clinic appointment. The assessment aims to exclude participants with no cognitive impairment from the study. 2. A baseline assessment - Participants will undergo a baseline visit to assess study eligibility. This will include a detailed clinical review. We are looking for patients who have cholinergic dysfunction but are not taking a cholinesterase inhibitor. Participants will undergo neurocognitive and neuropsychiatric tests(involving one interview/questionnaire, lasting up to 170 minutes, conducted at participant's home). Participants will an EEG (brain wave test) and blood tests (lasting 1 hour, at Clinical Ageing Research Unit [CARU], Campus for Ageing and Vitality). In a subset of patients (n=10) and controls (n=10) we will repeat the EEG on a different day to assess reliability of the index. 3. Randomisation - participants will be randomly assigned (like flipping a coin) to receive either donepezil (a cholinesterase inhibitor) or a placebo for 8 weeks followed by a period when no drug would be given (4 weeks) before switching over the other treatment group for 8 weeks. For example, if a participant is given donepezil in the initial period, he/she will receive placebo in the later stage and vice versa. Both donepezil and placebo will look exactly the same, hence both the participants and the researchers will not know at any point during the study whether they are receiving active treatment or placebo. Block randomisation will be used to ensure
1. Aged over 60 years 2. MoCA <26 3. Lewy Body Disease with cognitive impairment (one of the following): 3.1. PD-MCI: Meeting Level 1 PD-MCI criteria (screening stage) and Level 2 PD-MCI criteria (baseline assessment stage) with deficits > 2 SD below normative levels, or 3.2. For LB-MCI: Meeting LB-MCI criteria, or 3.3. Mild PD dementia, or 3.4. Dementia with Lewy body 4. English as a first language or fluent command of the English language as defined by the assessor. 5. A spouse, close relative or well established carer to accompany the subject to act as an informant (minimum contact twice weekly) and ensure medication compliance 6. Cholinesterase inhibitor and memantine naïve (not on a Cholinesterase inhibitor or memantine for the preceding 3 months) 7. If on anti-parkinsonian regime to have been on a stable regimen for at least 2 months
1. History of significant cerebrovascular disease 2. Presence of major cerebrovascular disease on brain imaging (severe leukoaraiosis or infarcts in strategic areas) 3. Other neurological diseases which may cause cognitive impairment e.g. a diagnosis of progressive supranuclear palsy, multiple system atrophy, or corticobasal degeneration, according to accepted diagnostic criteria 4. Presence of major depression 5. Physical co-morbidities including: history of severe gastrointestinal ulceration, severe asthma or obstructive pulmonary disease; systolic hypotension (< 90 mmHg); bradycardia (< 50 beats per minute); sick sinus syndrome; atrial or atrioventricular conduction block; QT interval prolongation (> = 450 ms) 6. Use of cognitive enhancing medications (e.g. cholinesterase inhibitors, memantine) 7. High dose benzodiazepines, antipsychotics or anticonvulsants 8. Use of anticholinergics with significant central effects e.g. oxybutynin 9. Contraindications to MR scanning (e.g. inability to lie flat for 30 minutes, claustrophobia, inability to tolerate a previous similar procedure, MR incompatible pacemaker) 10. Severe kidney disease 11. History of deep brain stimulation 12. Unstable and/or significant medical comorbidity likely to interfere with compliance 13. Significant functional deficits likely to interfere with compliance 14. Severe parkinsonism (Hoehn and Yahr stage IV or above) 15. Hypersensitivity to donepezil or piperidine derivatives