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Lewy body spectrum disorders are a common group of neurodegenerative diseases that cause memory loss, behavioural and motor disabilities that impair quality of life. Cognitive enhancers help people afflicted with these conditions. However, some people do not benefit from this treatment, while others experience serious side effects. Side effects and poor response lead to hospitalization and early institutionalization. Pharmacogenomics, the study of how DNA variation can influence drug effects, will be combined with functional changes in brain imaging in response to cognitive enhancers in patients with Lewy body disease. The goal is to develop a predictive test that can be administered in the clinic to aid physicians' choice of initial medication. This can reduce health care costs and improve treatment to Canadians suffering from these devastating disorders.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Parkinson's Disease Dementia | Participants in the Parkinson's Disease Dementia group:
|
| |
| Dementia with Lewy Bodies | Participants in the Dementia with Lewy Bodies group:
|
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cholinesterase Inhibitors (Rivastigmine, Aricept, Galantamine) | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline in perfusion brain SPECT at 6 months | 0 and 6 months | |
| Change from baseline in neuropsychological assessment scores at 6 months | 0 and 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Volumetric Brain MRI | Baseline |
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Inclusion Criteria:
Exclusion Criteria:
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Ontario, Canada.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sunnybrook Health Sciences Centre | Toronto | Ontario | M4N3M5 | Canada |
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| ID | Term |
|---|---|
| D020961 | Lewy Body Disease |
| D010146 | Pain |
| C537417 | Butyrylcholinesterase deficiency |
| ID | Term |
|---|---|
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| D002800 | Cholinesterase Inhibitors |
| D000068836 | Rivastigmine |
| D000077265 | Donepezil |
| D005702 | Galantamine |
| ID | Term |
|---|---|
| D004791 | Enzyme Inhibitors |
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
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Functional and tag SNPs in the following genes will be assessed:
acetylcholinesterase (ACHE); butyrylcholinesterase (BCHE); M1 muscarinic receptor (CHRM1); alpha7-nicotinic receptor (CHRNA7); Apolipoprotein E (ApoE); Cytochrome P450 2D6 (protein: CYP2D6 /gene: CYP2D6); CYP3A4; all genes related to blood pressure disregulation, white matter changes found on neuroimaging, and genes related to Lewy Body Spectrum disorders in general.
| D009422 | Nervous System Diseases |
| D003704 | Dementia |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D018678 | Cholinergic Agents |
| D018377 | Neurotransmitter Agents |
| D045505 | Physiological Effects of Drugs |
| D048448 | Phenylcarbamates |
| D002219 | Carbamates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D007189 | Indans |
| D007192 | Indenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D047151 | Amaryllidaceae Alkaloids |
| D000470 | Alkaloids |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |