A comparison of the efficacy of donepezil in Parkinson's disease with dementia and dementia with Lewy bodies.
BACKGROUND
Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB) overlap in phenomenology and neurochemical deficits. We hypothesised they would not differ in their response to the cholinesterase inhibitor donepezil.


METHODS
We recruited 70 subjects, 30 DLB and 40 PDD, in an open label study to compare the efficacy of donepezil in these two patient groups. They were assessed at baseline, 4, 12 and 20 weeks. The main outcome measures were the Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI) and motor sub-section of the Unified Parkinson's Disease Rating Scale (UPDRS III).


RESULTS
PDD patients were younger than DLB and had more severe parkinsonism at baseline. The groups were similar on all other variables of interest. By 20 weeks the mean MMSE score increased by 3.9 points in the DLB group and by 3.2 points in PDD. The mean NPI score reduced by 14.6 points for DLB and 12.0 points for PDD. These treatment effects were all significant compared to baseline (p < 0.001) but there were no significant between-group treatment differences (MMSE p = 0.56, NPI p = 0.39). UPDRS III motor scores did not change significantly from baseline values in either group. Although adverse effects were common (69%) they were usually mild and 64 patients (91%) completed the study. The four patients who did withdraw with adverse effects all had a PDD diagnosis.


CONCLUSIONS
Donepezil produced similar improvements in cognition and behaviour in DLB and PDD. This supports the hypothesis that the two disorders are closely related clinically and neurobiologically. Larger scale, placebo controlled clinical trials are needed to provide an evidence base to guide the clinical use of cholinesterase inhibitors in Lewy body disease.
Thomas
Alan J
AJ
Institute for Ageing and Health, University of Newcastle upon Tyne, Wolfson Research Centre, Newcastle General Hospital, Newcastle upon Tyne, UK.
Burn
David J
DJ
Rowan
Elise N
EN
Littlewood
Elizabeth
E
Newby
Jane
J
Cousins
David
D
Pakrasi
Sanjeet
S
Richardson
Jonathan
J
Sanders
Jonathan
J
McKeith
Ian G
IG
D000367:Age Factors; D000368:Aged; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D003704:Dementia / Q000150:complications / Q000188:drug therapy* / Q000523:psychology; D000077265:Donepezil; D005260:Female; D006801:Humans; D007189:Indans / Q000009:adverse effects / Q000627:therapeutic use*; D020961:Lewy Body Disease / Q000188:drug therapy / Q000523:psychology; D008297:Male; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000150:complications / Q000188:drug therapy* / Q000523:psychology; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil