Efficacy of donepezil on maintenance of activities of daily living in patients with moderate to severe Alzheimer's disease and the effect on caregiver burden.
OBJECTIVE
This study investigated the efficacy of donepezil treatment on activities of daily living (ADLs) and social functioning in patients with moderate to severe Alzheimer's disease (AD) and the possible benefits of this treatment on caregiving time and stress levels.


METHODS
Randomized, double-blind, placebo-controlled, multinational study.


METHODS
Patients resided in the community or in assisted living facilities who did not require skilled 24-hour nursing care.


METHODS
Two hundred ninety patients with moderate to severe AD (baseline standardized Mini-Mental State Examination score of 5-17).


METHODS
Donepezil (5 mg/d for 4 weeks and 10 mg/d per clinician's judgment thereafter) or placebo for 24 weeks.


METHODS
ADLs were assessed using the Disability Assessment for Dementia (DAD), the modified instrumental activities of daily living (IADL) scale (IADL+), and the modified Physical Self Maintenance Scale (PSMS+). Caregiver time spent assisting patients with basic and instrumental ADLs was recorded as part of the IADL+ and PSMS+ scales. Patients' social behavior was evaluated through the use of a caregiver diary that captured observations of patients' motivation, interactions, and engagement. Caregivers were evaluated for their levels of caregiver stress with a modified, multiple-item Caregiver Stress Scale (CSS). For each outcome measure, the mean change from baseline at Week 24 using a last observation carried forward (LOCF) analysis was calculated.


RESULTS
IADL+ and PSMS+ mean change from baseline scores for donepezil-treated patients showed a slower decline during the study than placebo-treated patients (Week 24 LOCF mean treatment differences: IADL+ = 6.83, P <.0001; PSMS+ = 1.32, P =.0015). Significant differences between the groups in favor of donepezil were observed on the DAD for instrumental and basic ADLs and on the three components required for the completion of each ADL: initiation, planning and organization, and effective performance. At baseline, caregivers of patients treated with donepezil (n = 141) did not differ significantly from caregivers of patients treated with placebo (n = 146) with respect to demographics or mean total scores on the CSS. At Week 24 LOCF, the overall distribution of caregiver ratings on each of the three caregiver diary items favored donepezil-treated patients over placebo-treated patients (P <.005). At Week 24 LOCF, mean change from baseline scores for CSS total and individual domain scores (all domains except caregiving competence, personal gain, and management of distress) were better for caregivers of donepezil-treated patients than for those of placebo-treated patients (CSS total, mean treatment difference = 1.82). Caregivers of donepezil-treated patients reported spending less time assisting with ADLs than caregivers of placebo-treated patients (mean difference = 52.4 min/d).


CONCLUSIONS
Donepezil demonstrated a significantly slower decline than placebo in instrumental and basic ADLs in these patients with moderate to severe AD. The ADL benefits in AD patients treated with donepezil were associated with less caregiving time and lower levels of caregiver stress.
Feldman
Howard
H
Division of Neurology, UBC Hospital, Clinic for Alzheimer's Disease and Related Disorders, Vancouver, British Columbia, Canada. hfeldman@interchange.ubc.ca
Gauthier
Serge
S
Hecker
Jane
J
Vellas
Bruno
B
Emir
Birol
B
Mastey
Vera
V
Subbiah
Ponni
P
D000203:Activities of Daily Living; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology*; D017028:Caregivers / Q000523:psychology*; D017281:Cost of Illness; D000077265:Donepezil; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018697:Nootropic Agents / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use*; D012919:Social Behavior; D013312:Stress, Physiological; D013997:Time Factors; D016896:Treatment Outcome
D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil