Effects of donepezil on activities of daily living: integrated analysis of patient data from studies in mild, moderate and severe Alzheimer's disease.
BACKGROUND
We aimed to develop a standardization method to pool data recorded on different activities of daily living (ADL) scales in order to reduce variability of functional outcome data from Alzheimer's disease (AD) clinical trials and to better evaluate the effect of donepezil treatment on function in patients with AD.


METHODS
Based on pre-specified criteria, six studies were selected from among all donepezil clinical trials in AD. Individual items from nine ADL scales used in these trials were mapped to a standardized functional scale comprising 12 domains (six basic, six instrumental); scores were transformed to a 0-100 scale. External validation of this scale yielded a concordance rate of 90.8%. For each domain, mean change from baseline to 24 weeks in the placebo and donepezil groups was compared for the total population and for subgroups stratified by baseline disease severity. Study settings included outpatient, assisted living, and skilled nursing facilities. Participants comprised 2183 patients (donepezil, 1261; placebo; 922) with baseline Mini-mental State Examination (MMSE) scores 5-26.


RESULTS
Significant treatment differences favoring donepezil were observed for five items (two instrumental and three basic). Patients with moderate AD at baseline (MMSE 10-17) demonstrated the greatest treatment effect.


CONCLUSIONS
Functional data were successfully pooled using standardizing methodology. A beneficial effect of donepezil treatment on function was demonstrated using this standardized functional scale. Similar analyses from studies with other anti-dementia drugs may help to determine the generalizability of these findings and potentially encourage use of functional assessment as a clinical tool.
McGill Center for Studies in Aging, Douglas Mental Health University Institute, Douglas Hospital, Verdun, QC, Canada. serge.gauthier@mcgill.ca
Serge
S
Gauthier
Oscar L
OL
Lopez
Gunhild
G
Waldemar
Roy W
RW
Jones
Jeffrey
J
Cummings
Richard
R
Zhang
Rachel
R
Schindler
Elias
E
Schwam
D000203:Activities of Daily Living / Q000145:classification* / Q000523:psychology; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology; D000553:Ambulatory Care; D040561:Assisted Living Facilities; D004185:Disability Evaluation; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D008297:Male; D008609:Mental Status Schedule / Q000706:statistics & numerical data; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D018697:Nootropic Agents / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use*; D011594:Psychometrics; D016032:Randomized Controlled Trials as Topic; D012866:Skilled Nursing Facilities
D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil