Clinical trials in Parkinson's disease dementia and dementia with Lewy bodies.
Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB) are pathological overlapping and important causes of dementia for which clinical trials are in their infancy. Cholinesterase inhibitors may be of benefit in DLB and PDD, as suggested by placebo-controlled clinical trials of rivastigmine and donepezil. The anti-psychotic agent clozapine has been of benefit in PD and PDD, but other agents, such as quetiapine, require adequate assessment. Barriers to trials include pathological overlap that can lead to inaccuracies in clinical diagnosis, unavailability of a consensus definition for PDD, unanswered questions regarding natural history and the paucity of validated outcome measures. Motor impairment must be considered in patients with PDD and DLB; conversely, cognitive impairment should be assessed in trials targeting motor impairment in advanced PD. Potential targets for treatment include onset of dementia, cognitive impairment, behavioral impairment, functional decline, falls, nursing home placement, mortality, quality of life and economic impact. Biomarkers including neuroimaging and cerebrospinal fluid markers are not currently established. At present PDD and DLB are distinct entities by definition. Future studies, including clinical trials and biomarker studies, will help to further define the clinical and therapeutic implications of this distinction.
Camicioli
Richard
R
Glenrose Rehabilitation Hospital, Edmonton, AB, Canada.
Gauthier
Serge
S
D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D002986:Clinical Trials as Topic / Q000379:methods / Q000592:standards* / Q000639:trends*; D003072:Cognition Disorders / Q000175:diagnosis; D003937:Diagnosis, Differential; D006801:Humans; D020961:Lewy Body Disease / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D009483:Neuropsychological Tests / Q000592:standards; D010043:Outcome and Process Assessment, Health Care / Q000592:standards*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D012107:Research Design
D014150:Antipsychotic Agents; D002800:Cholinesterase Inhibitors