Patients who met the consensus diagnostic criteria2 for probable DLB were recruited from 48 psychiatric or neurological specialty centers throughout Japan from October 2007 to February 2010. Diagnosis of each patient was validated after discussion by the central committee. Outpatients (≥50 years old) with mild to moderate-severe dementia (10-26 on the Mini-Mental State Examination [MMSE]18 and Clinical Dementia Rating19 ≥0.5) and with behavioral symptoms (Neuropsychiatric Inventory-plus [NPI-plus] ≥8) were eligible. NPI-plus is a 12-item version of the NPI, with the original 10 items supplemented by 2 DLB-relevant domains of sleep and cognitive fluctuation.11 , 20 , 21 Patients had caregivers who routinely stayed with them at least 3 days per week and 4 hours per day, provided information for this study, assisted compliance with treatment, and escorted patients to required visits.
Exclusion criteria included Parkinson disease diagnosed at least 1 year prior to the onset of dementia; focal vascular lesions on magnetic resonance imaging or computed tomography that might cause cognitive impairment; other neurological or psychiatric diseases; clinically significant systemic disease; complications or history of severe gastrointestinal ulcer, severe asthma, or obstructive pulmonary disease; systolic hypotension (<90mmHg); bradycardia (<50m−1); sick sinus syndrome; atrial or atrioventricular conduction block; QT interval prolongation (≥450 milliseconds); hypersensitivity to donepezil or piperidine derivatives; severe parkinsonism (Hoehn and Yahr score ≥ IV)22 ; and treatment with ChEIs or any investigational drug within 3 months prior to screening. ChEIs, antipsychotic agents, and antiparkinson drugs other than L-dopa or dopamine agonists were not allowed during the study.
Written informed consent was obtained from the patient (if at all possible) and his/her caregiver before initiating the study procedures. The study was conducted in accordance with the principles of the Declaration of Helsinki. The protocol was approved by the institutional review board at each center.
Exclusion criteria included Parkinson disease diagnosed at least 1 year prior to the onset of dementia; focal vascular lesions on magnetic resonance imaging or computed tomography that might cause cognitive impairment; other neurological or psychiatric diseases; clinically significant systemic disease; complications or history of severe gastrointestinal ulcer, severe asthma, or obstructive pulmonary disease; systolic hypotension (<90mmHg); bradycardia (<50m−1); sick sinus syndrome; atrial or atrioventricular conduction block; QT interval prolongation (≥450 milliseconds); hypersensitivity to donepezil or piperidine derivatives; severe parkinsonism (Hoehn and Yahr score ≥ IV)22 ; and treatment with ChEIs or any investigational drug within 3 months prior to screening. ChEIs, antipsychotic agents, and antiparkinson drugs other than L-dopa or dopamine agonists were not allowed during the study.
Written informed consent was obtained from the patient (if at all possible) and his/her caregiver before initiating the study procedures. The study was conducted in accordance with the principles of the Declaration of Helsinki. The protocol was approved by the institutional review board at each center.
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