Healthy ageing, amnesic mild cognitive impairment and mild to moderate Alzheimer's dementia. Mental and Behavioural Disorders Alzheimer's Disease
Conditions
Interventions
Current interventions as of 06/07/2020:
A cohort of healthy control participants undergo block randomisation into groups, who will receive each treatment in a different order. Participants will visit
Sponsors
University of Bristol
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current participant inclusion criteria as of 06/07/2020: 1. Native or fluent English speakers (highly proficient in English language) 2. Normal or corrected to normal vision 3. Aged 65 years or older 4. Participants must have mental capacity to consent, and score above 11/30 in the Montreal Cognitive Assessment test Previous participant inclusion criteria: 1. Native or fluent English speakers (highly proficient in English language) 2. Normal or corrected to normal vision 3. Aged 65 years or older (may recruit younger patients if age-matched healthy control can be found) 4. Diagnosis of Mild cognitive impairment (MCI) or mild Alzheimer's Disease (AD) 5. Participants must have mental capacity to consent, and score above 11/30 in the Montreal Cognitive Assessment test
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 20/04/2018: 1. The participants must not have: 1. 1. Clinically significant neurological or psychiatric diagnoses, other than MCI or mild AD for the patient group. This will be assessed by self-report and questionnaires during the screening visit 1.2. Known posterior cortical atrophy (mainly relevant for MCI and AD, who will have had a brain scan as a part of the diagnostic procedure) 1.3. Clinically significant sleep problems in the past year 1.4. An undiagnosed skin lesion. Participants will be asked about this. 1.5. Known sensitivity to levodopa, ropinirole, benserazide, or domperidone 1.6. Known lactose intolerance, galactosemia or glucose/galactose malabsorption 1.7. Known galactose intolerance 1.8. Known Lapp lactase deficiency 1.9. Diagnosis of Huntington’s Chorea 1.10. Intention tremor. This will be screened for by a trained investigator 1.11. Known prolactin-releasing pituitary tumour (prolactinoma) 1.12 Diagnosis of glaucoma 1.13 A history of, or current, malignant melanoma 1.14 Diagnosed diabetes 1.15 Known osteomalacia 1.16 Severe endocrine, hepatic, renal, pulmonary, or cardiac disorder 1.17 Diagnosed electrolyte disturbances 1.18 Known peptic ulcers 1.19 History of a heart-attack or prolongation of cardiac conduction intervals, or any other cardiac problems as taking domperidone increases risk of said problems. An ECG will be taken at the screening visit and heart-rate and blood pressure will be monitored before and after drug administration, as specified elsewhere in this protocol. 1.20. Current cancer treatment 1.21. End stage renal disease or severe renal impairment 1.22. Diagnosed hepatic impairment 1.23 Pregnant women and women of childbearing potential not using adequate contraception will be excluded in line with the Madopar SmPC 2. The participant must not be taking: 2.1 Dopaminergic medications 2.2 Noradrenergic, serotonergic, or anticholinergic medications, except if the participant has been on stable treatment (at least 3 months) for pain or mood disorders 2.3 Monoamine oxidase inhibitors (MAO-I), except if selective MAO-A or MAO-B inhibitors are given. MAO-A and MAO-B inhibitors given together are equivalent to non-selective MAO-inhibition and therefore volunteers taking both MAO-A and MAO-B will not be included in this study 2.4. Cholinesterase inhibitors, except if the participant has been on stable treatment (at least 3 months) 2.5. Antihypertensive (blood pressure) drugs containing reserpine 2.6. Ferrous sulphate on the day of testing 2.7. Opioids or sympathomimetics (e.g. amphetamines, epinephrine/adrenaline) 2.8. Diazepam 2.9 Ketoconazole, erythromycin or CYP3A4 inhibitors (e.g. fluoconazole, voriconazole, clarithromycin, amiodarone, telithryomycin) 2.10. Antibiotics 2.11. Hormone replacement therapy 2.12. Anti-fungal agents (pentamidine) 2.13. Anti-malarial agents 2.14. Gastro-intestinal medicines 2.15. Antihistaminics 2.16. AIDS/HIV medications 2.17. If a participant takes antacids or antisecretory agents they should not be taken at the same time as domperidone (but these participants can be included if the medication can be taken at a different time) 2.18. Any medication known to interfere with co-beneldopa or domperidone Original exclusion criteria: 1. The participants must not have: 1. 1. Clinically significant neurological or psychiatric diagnoses, other than MCI or mild AD for the patient group. This will be assessed by self-report and questionnaires during the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The change in behavioural performance on memory and learning tasks (number of words recalled) after 12 hours and after 3 and 5 days after medication. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Time spent (in minutes) in different sleep stages as measured from EEG of sleep during the night following administration 2. Hippocampal subfield volume and shape to be measured using MRI and fMRI. Structural MRI is taken at baseline, fMRI is taken between 1 and 3 hours following drug administration 3. White matter tractography as measured by diffusion weighted imaging 4. Functional correlativity (Pearson's r) between VTA BOLD and hippocampus BOLD signals 5. Sensory preconditioning/reinforcement learning task the ratio of choices of rewarded actions compared to non-rewarded 6. Attention and motor learning tasks raw reaction times measured at baseline, 30 minutes after dosing, 12 hours after dosing | — |
Countries
England, United Kingdom
Outcome results
None listed