Grant: CIHR Clinician Scientist - Phase 1

Dementia with Lewy Bodies (DLB) and Parkinson¿s Disease with Dementia (PDD) are common neurodegenerative disorders which cause significant disability, reduced quality of life and eventually death in the elderly. Treatment with drugs known as cholinesterase inhibitors (ChEIs) remains the mainstay of therapy for the cognitive and behavioural symptoms, which reflect profound deficits in the brain chemical, acetylcholine. However, there is a substantial amount of variability from person to person in response and side effects to these drugs. That is, some people have a good response; some have a poor response while others experience side effects at the same dose of a given ChEI. This limits the use of these drugs. The drug being studied in this proposal is rivastigmine which is the only ChEI with proven efficacy in treating DLB and PDD. Using functional neuroimaging and detailed cognitive assessments, the proposed study attempts to identify genetic variation in DNA that may contribute to the observed variability in response to rivastigmine in DLB and PDD.