Donepezil treatment of severe Alzheimer's disease in nursing home settings. A responder analysis.
OBJECTIVE
Our objective was to define clinically meaningful outcomes in donepezil versus placebo treatment in severe Alzheimer's disease (AD) and to describe characteristics of responders.


METHODS
Analyses were performed on data from a 6-month, double-blind, parallel-group, placebo-controlled study on the efficacy of donepezil in 248 nursing home residents. Various individual responses were defined as stabilisation or improvement on the Severe Impairment Battery (SIB), Alzheimer's Disease Cooperative Study-activities of daily living scale (ADCS-ADL), Mini-Mental State Examination, Neuropsychiatric Inventory (NPI) or Clinical Global Impression of Improvement. Three composite measures were defined by combining the individual response criteria on these outcomes. The impact of baseline disease severity and of concomitant use of psychotropic drugs was also analysed.


RESULTS
At 6 months, greater proportions of patients defined as responders to donepezil on individual efficacy measures showed significant stabilisation or improvement compared with placebo on the SIB (>or=0, >or=4 or >or=7 points) and Mini-Mental State Examination (>or=0 or >or=3 points), and positive trends on the ADCS-ADL-severe (>or=3 points) and the NPI cluster based on mood items. All 3 composite measures of efficacy showed a significantly higher proportion of responders in the donepezil group. The responders had a similar distribution between the 2 subgroups of cognitive and functional disease severity at baseline. The donepezil-treated patients taking psychotropic drugs showed significantly greater improvement on the SIB, less deterioration on the ADCS-ADL, and had higher Clinical Global Impression of Improvement scores and a trend towards lower NPI scores. The baseline demographic and clinical profile did not differ between the non-responders and responders on the composite outcome measures.


CONCLUSIONS
The results demonstrate that donepezil treatment of patients with severe AD consistently shows stabilisation or improvement across multiple outcome measures in individual patients, including cognitive, functional and behavioural symptoms.
Jelic
Vesna
V
Division of Geriatric Medicine, Department of NVS, Karolinska Institutet, Karolinska University Hospital-Huddinge, Stockholm, Sweden. vesna.jelic@ki.se
Haglund
Anders
A
Kowalski
Jan
J
Langworth
Sven
S
Winblad
Bengt
B
D000203:Activities of Daily Living; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology*; D001519:Behavior / Q000502:physiology; D015992:Body Mass Index; D003071:Cognition / Q000502:physiology; D000077265:Donepezil; D005260:Female; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000627:therapeutic use*; D009735:Nursing Homes; D010880:Piperidines / Q000627:therapeutic use*; D016896:Treatment Outcome
D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil