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Clinical Trials in Parkinson's Disease Dementia and Dementia with Lewy Bodies

  • Richard Camicioli (a1) and Serge Gauthier (a2)

Abstract

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.

RÉSUMÉ:

La maladie de Parkinson avec démence (MPD) et la démence à corps de Lewy (DCL) sont des causes importantes de démence qui se chevauchent au point de vue pathologique. Les essais cliniques sur ces deux types de démence en sont au tout début. Selon des essais cliniques contrôlés par placebo portant sur la rivastigmine et le donépézil, les inhibiteurs de la cholinestérase pourraient être bénéfiques dans la DCL et la MPD. Les patients atteints de MP et de MPD ont tiré un bénéfice du traitement par la clozapine, un anti-psychotique, mais d'autres agents tels la quétiapine n'ont pas été évalués adéquatement. Plusieurs obstacles devront être surmontés, notamment le chevauchement des pathologies qui peut entraîner des erreurs diagnostiques, le manque de consensus sur la définition de la MPD, des questions non résolues concernant leur évolution naturelle et le manque de critères d'évaluation validés. Chez les patients atteints de MPD et de DCL, on doit tenir compte de l'atteinte motrice et dans la MPD en phase avancée, l'atteinte cognitive devrait être évaluée au cours d'essais cliniques ciblant l'atteinte motrice. Le début de la démence, l'atteinte cognitive, l'atteinte comportementale, le déclin fonctionnel, les chutes, le placement en établissement de soins prolongés, la mortalité, la qualité de vie et l'impact économique sont des cibles pour l'évaluation du traitement. Les biomarqueurs tels les marqueurs de neuro-imagerie et ceux du liquide céphalorachidien ne sont pas validés. Pour l'instant, la MPD et la DCL sont des entités distinctes par définition. D'autres études, en particulier des essais cliniques et des études de biomarqueurs aideront à mieux définir les implications cliniques et thérapeutiques de cette distinction.

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Copyright

Corresponding author

E223, Glenrose Rehabilitation Hospital, 10230 - 111th Avenue, Edmonton, Alberta, T5G 0B7, Canada.

References

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Clinical Trials in Parkinson's Disease Dementia and Dementia with Lewy Bodies

  • Richard Camicioli (a1) and Serge Gauthier (a2)

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