KUD--a scale for clinical evaluation of moderate-to-severe dementia.

AIM: To develop a test of cognitive performance in persons with moderate-to-severe dementia. BACKGROUND: Various instruments are used to assess the course of dementia and to evaluate treatments in persons with dementia. Most neuropsychological assessments are inappropriate for measuring cognitive abilities in persons with severe dementia, because these persons perform at floor level in such measurements. DESIGN: A cross-sectional research design. METHODS: The test (Clinical Evaluation of Moderate-to-Severe Dementia; Swedish acronym: KUD) was developed from a pool of 25 test items with the final KUD consisting of 15 items. Reliability and validity were established using 220 subjects (with various dementia diagnoses) with scores of Mini-Mental State Examination between 0-20. Approximately two weeks after the first test, 116 of the original 220 subjects were retested. RESULTS: A factor analysis with the 15-item scale revealed an interaction factor comprising three items and a cognitive performance factor with 12 items. The internal consistence reliability was 0·93 for the KUD (Cronbach's alpha). Test-retest reliability was also high (0·92) and correlation between the KUD and the MMSE (≤20) was high (r=0·80). CONCLUSION: The KUD seems to be a valid, reliable performance-based assessment scale for measuring cognitive performance in persons with MMSE score below 12 or 15 points. RELEVANCE TO CLINICAL PRACTICE: It is of outmost interest that cognitive performance can be easily followed for persons with moderate-to-severe dementia in, for example, drug therapies and other therapies, but also in terms of treatment of and support to the person based on his or her abilities.

Donepezil treatment of severe Alzheimer's disease in nursing home settings. A responder analysis.

BACKGROUND/AIMS: 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. CONCLUSION: 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.

Donepezil in patients with severe Alzheimer's disease: double-blind, parallel-group, placebo-controlled study.

BACKGROUND: The cholinesterase inhibitor donepezil is used to treat mild-to-moderate Alzheimer's disease. Its efficacy in severe dementia has not been assessed and is controversial. Our aim was to ascertain the effectiveness of donepezil in patients with severe Alzheimer's disease, by focusing primarily on cognition and activities of daily living. METHODS: We did a 6-month, double-blind, parallel-group, placebo-controlled study in 248 patients with severe Alzheimer's disease (mini mental state examination score 1-10) who were living in assisted care nursing homes ran by trained staff in Sweden. We assigned patients oral donepezil (5 mg per day for 30 days then up to 10 mg per day thereafter, n=128) or matched placebo (n=120). Our primary endpoints were change from baseline to month 6 in the severe impairment battery (SIB) and modified Alzheimer's Disease Cooperative Study activities of daily living inventory for severe Alzheimer's disease (ADCS-ADL-severe). We analysed outcomes for patients with data at baseline and at one or more other timepoints (modified intent-to-treat population) with last observation carried forward used to replace missing data. FINDINGS: 95 patients assigned donepezil and 99 patients assigned placebo completed the study. Patients treated with donepezil improved more in SIB scores and declined less in ADCS-ADL-severe scores at 6 months after initiation of treatment compared with baseline than did controls (least squares [LS] mean difference, 5.7, 95% CI 1.5-9.8; p=0.008, and 1.7, 0.2-3.2; p=0.03, respectively). The incidence of adverse events was comparable between groups (donepezil 82% [n=105] vs placebo 76% [n=91]), with most being transient and mild or moderate in severity. More patients discontinued treatment because of adverse events in the donepezil group (n=20) than in the placebo group (n=8). INTERPRETATION: Donepezil improves cognition and preserves function in individuals with severe Alzheimer's disease who live in nursing homes.

An economic evaluation of donepezil in mild to moderate Alzheimer's disease: results of a 1-year, double-blind, randomized trial.

The costs and consequences of donepezil versus placebo treatment in patients with mild to moderate Alzheimer's disease (AD) were evaluated as part of a 1-year prospective, double-blind, randomized, multinational clinical trial. Patients received either donepezil (n = 142; 5 mg/day for 28 days followed by 10 mg/day according to the clinician's judgement) or placebo (n = 144). Unit costs were assessed in 1999 Swedish kronas (SEK) and converted to US dollars (USD). Donepezil-treated patients gained functional benefits relative to placebo on the Progressive Deterioration Scale (p = 0.042) and Instrumental Activities of Daily Living scale (p = 0.025) at week 52. Caregivers of donepezil-treated patients spent an average of 400 h less annually providing care than caregivers of placebo-treated patients. Mean annual healthcare costs were SEK 137,752 (USD 16,438) per patient for the donepezil group and SEK 135,314 (USD 16,147) in the placebo group. With the average annual cost of donepezil at SEK 10,723 (USD 1,280) per patient, the SEK 2,438 (USD 291) cost difference represented a 77% cost offset. When caregiver time and healthcare costs were included, mean annual costs were SEK 209,244 (USD 24,969) per patient in the donepezil group and SEK 218,434 (USD 26,066) in the placebo group, a total saving associated with donepezil treatment of SEK 9,190 (USD 1,097) per patient [95% CI of SEK -43,959 (USD -5,246), SEK 25,581 (USD 3,053); p = 0.6]. The positive effects on the efficacy outcome measures combined with no additional costs from a societal perspective indicate that donepezil is a cost-effective treatment, representing an improved strategy for the management of patients with AD.