Alzheimer Disease: Wimo A

Winblad B, Wimo A, Möbius HJ, Fox JM, Fratiglioni L. · No affiliation provided · Int J Geriatr Psychiatry. · Pubmed #10556861 No free full text.

This publication has no abstract.

Kalaria RN, Maestre GE, Arizaga R, Friedland RP, Galasko D, Hall K, Luchsinger JA, Ogunniyi A, Perry EK, Potocnik F, Prince M, Stewart R, Wimo A, Zhang ZX, Antuono P, Anonymous00415. · Institute for Ageing and Health, Newcastle General Hospital, Newcastle upon Tyne, UK. · Lancet Neurol. · Pubmed #18667359 No free full text.

Abstract: Despite mortality due to communicable diseases, poverty, and human conflicts, dementia incidence is destined to increase in the developing world in tandem with the ageing population. Current data from developing countries suggest that age-adjusted dementia prevalence estimates in 65 year olds are high (>or=5%) in certain Asian and Latin American countries, but consistently low (1-3%) in India and sub-Saharan Africa; Alzheimer's disease accounts for 60% whereas vascular dementia accounts for approximately 30% of the prevalence. Early-onset familial forms of dementia with single-gene defects occur in Latin America, Asia, and Africa. Illiteracy remains a risk factor for dementia. The APOE epsilon4 allele does not influence dementia progression in sub-Saharan Africans. Vascular factors, such as hypertension and type 2 diabetes, are likely to increase the burden of dementia. Use of traditional diets and medicinal plant extracts might aid prevention and treatment. Dementia costs in developing countries are estimated to be US$73 billion yearly, but care demands social protection, which seems scarce in these regions.

Wimo A. · Department of Neurobiology, Care and Society, Karolinska University Hospital, Stockholm, Sweden. · Int Psychogeriatr. · Pubmed #17346367 No free full text.

Abstract: The growing interest in analyzing the cost-effectiveness of interventions presents a challenge to anyone involved in dementia research. Although not yet often expressed as a formal requirement, drug authorities and budget holders also wish to have information on cost effectiveness. Clinical outcomes must therefore be combined with outcomes suitable for cost effectiveness analysis. However, issues about cost effectiveness are seldom included in empirical clinical trials, but are more often analyzed using modeling approaches. Clinical researchers and economists need to bridge these areas of potential conflict when long-term cost effectiveness is being considered. Randomized clinical trials (RCTs), observational studies, register data and economic models all have their advantages and drawbacks, and in making statements about cost effectiveness it is necessary to make a comprehensive judgment based on several methodological approaches. RCTs with a duration of at least 12 months should include assess-ments of resource utilization, and outcomes should offer a link to population-based cohort studies to discuss generalizability (e.g. a cognitive measure avail-able both in trials and cohort studies, such as the Mini-mental State Examination (MMSE), staging instruments, quality of life instruments) of the costs, while also serving as one source of modeling. Both dementia-specific and generic quality of life instruments are required. Models are necessary but must be transparent so that the assumptions on which the models are built can be critically analyzed.

Wimo A. · Division of Geriatric Epidemiology, Neurotec, Karolinska Institutet, Stockholm, Sweden. · Drugs Aging. · Pubmed #15040756 No free full text.

Abstract: Cholinesterase inhibitors have been available for the treatment of Alzheimer's disease since 1993. They have significantly positive effects on cognitive functioning and other domains of functional capacity, such as activities of daily life in terms of efficacy, but the clinical value of these effects are under discussion. Cholinesterase inhibitors may also influence behavioural and psychological symptoms in Alzheimer's disease. Cholinesterase inhibitors are also regarded as rather expensive and, therefore, the question of cost effectiveness is essential. Pharmacoeconomic evaluations of cholinesterase inhibitors have so far been conducted in retrospect on efficacy data from prospective randomised clinical trials combined with economic data from other sources. There are no published specific cost-effectiveness studies of cholinesterase inhibitors which prospectively collected empirical data on costs and outcomes. There is only one published randomised clinical trial with such empirical data with a cost consequence analysis design, indicating cost neutrality. Several types of models to describe the long-term effects have been published, indicating cost effectiveness. However, due to methodological considerations, the validity of these models is difficult to judge. A research agenda for the cost effectiveness of cholinesterase inhibitors is proposed, including long-term studies with empirical data on resource use, costs and outcomes, studies on quality of life, informal care and behavioural and psychological symptoms, combination and comparative studies on mild cognitive impairment.

Winblad B, Wimo A, Almkvist O. · Karolinska Institutet, Alzheimer Research Center, Department of Clinical Neuroscience, Huddinge University Hospital, Sweden. · Dement Geriatr Cogn Disord. · Pubmed #10971046 No free full text.

Abstract: As the interest in Alzheimer's disease (AD) and its treatment has grown, so has the sophistication of clinical trials of potential drug therapies. In particular, interest has focused on outcomes used to assess the severity of the illness and the effectiveness of treatment. This paper reviews the assessments that are used frequently in trials of AD therapy and describes further measures that may be of value in determining effective treatments for the disease. The review concludes that it is important that evaluation of drug effects on AD is not confined solely to the assessment of cognitive function. To gain a true overview of the impact of AD on patients, carers and society, areas such as activities of daily living, caregiver burden, quality of life, behavioural symptoms and resource utilization need to be comprehensively determined.

Winblad B, Wimo A. · Department of Clinical Neuroscience, Occupational Therapy and Elderly Care, Karolinska Institute, Stockholm, Sweden. · Alzheimer Dis Assoc Disord. · Pubmed #10622674 No free full text.

Abstract: The symptomatology of Alzheimer disease (AD), its longevity, and associated cost make it an extremely challenging disease for individuals, their families, health care, and social support systems. Moreover, the expanding aging population worldwide means that strategies to contain costs are an urgent priority. As the largest component of the direct costs of AD is due to the cost of institutionalization, cost-containment strategies have focused on ways to maintain the AD patient in the community for as long as possible. Disease severity is a strong predictor of institutionalization, and patients' cognitive function (in the form of their Mini-Mental State Examination score) is frequently used as a prognostication of their living environment, and thus the overall cost of their care. Strategies to maintain patients at home are directed at either the patient's symptoms or the caregiver's ability to cope with those symptoms and the responsibilities of caregiving. Examples of strategies directed at the caregiver include education and support programs. Drug treatments, notably acetylcholinesterase inhibitors, present the best option for improving patient function, thereby preserving patient autonomy. A number of preliminary studies, whose results are summarized here, have demonstrated that the use of the acetylcholinesterase inhibitors tacrine, metrifonate and donepezil, and the glial cell modulator, propentofylline, results in reductions in the overall costs of care. Most health economic studies have focused only on comparison of the costs associated with paying for administering a treatment and the savings produced by postponed institutionalization. However, there is a growing realization that some measures of the quality of life or well-being of both patient and caregiver should also be incorporated. Thus, the health economics of dementia is an extremely complex area of study that is rapidly growing, due to the likelihood that cost-effectiveness will form the basis for future reimbursement decisions.

Wimo A, Winblad B, Grafstrom M. · Research Unit of Primary Health Care in Nordanstig, Bergsjö, Sweden. · Int J Geriatr Psychiatry. · Pubmed #10389036 No free full text.

Abstract: The social consequences of Alzheimer's disease are highlighted in this review with regard to impact on family situation, a changing treatment context caused by demographic changes, reorganization of long-term care, a financial crisis in the public health systems and the introduction of antidementia drugs. In the early phase of dementia there may be significant consequences for the patients and the family members which are largely unrecognized by the healthcare system. As the disease progresses, the impact on caregivers in terms of physical and emotional burden, financial and employment status may be enormous. The current care provision in Sweden, the UK and The Netherlands is described. Innovative care alternatives and strategies may improve the situation. The introduction of antidementia drugs such as the acetylcholine esterase inhibitors may also contribute to improved circumstances for patients and caregivers. There is still a great need for further research in this field.

Wimo A, Winblad B, Shah SN, Chin W, Zhang R, McRae T. · Karolinska Institutet, Huddinge, Sweden. · Curr Med Res Opin. · Pubmed #15324524 No free full text.

Abstract: OBJECTIVE: To assess the impact of donepezil treatment compared with placebo on caregiver time spent assisting patients with Alzheimer's disease (AD). RESEARCH DESIGN AND METHODS: Patient and caregiver data were collected as part of a 1-year, prospective, double-blind, randomized, placebo-controlled trial. The Resource Utilization in Dementia (RUD) questionnaire was used to record caregiver time at study baseline and at Weeks 12, 24, 36, and 52. This analysis focuses solely on those caregivers who were actively (> 0 h/day reported on the RUD) providing care at study baseline. MAIN OUTCOME MEASURES: The change in time relative to baseline that caregivers spent assisting patients over the course of the study. RESULTS: The active caregiver population was composed of 96 caregivers of donepezil-treated patients and 94 caregivers of patients receiving placebo. Over the course of the 1-year study, and as the condition of the AD patients deteriorated, it was expected that caregiver time would increase. As expected, after 52 weeks, caregivers of placebo patients were providing almost 2 h each day (106.8 min) more care than they had done at study baseline. For those caregivers of donepezil-treated patients, although they were spending more time caring than they had done at study baseline, their time burden had only increased by 42.6 min more each day. This difference in caring time between the 2 groups, relative to baseline at Week 52, was 1.1 h (64.2 min) each day, and was significant (p = 0.03). CONCLUSION: Caregiver time devoted to helping an AD patient typically increases with the severity of the disease. By helping the patient maintain his/her ability to perform activities of daily living for longer, treatment with donepezil is not only beneficial to the patient, but also has positive time-burden implications for the caregiver.

Wimo A, Winblad B, Stöffler A, Wirth Y, Möbius HJ. · Division of Geriatric Epidemiology (Sector of Health Economy), Neurotec, Karolinska Institute, Huddinge, Sweden. · Pharmacoeconomics. · Pubmed #12627986 No free full text.

Abstract: BACKGROUND: Alzheimer's disease (AD) is a devastating illness that causes enormous emotional stress to affected families and is associated with substantial medical and nonmedical costs. OBJECTIVE: To determine the effects of 28 weeks of memantine treatment for patients with AD on resource utilisation and costs. STUDY DESIGN AND METHODS: Multicentre, prospective, double-blind, randomised, placebo-controlled clinical trial performed in the US. The Wilcoxon-Mann-Whitney test was used to examine the resource utilisation variables and logistic regression models were used for multivariate resource utilisation analyses. Analysis of covariance (ANCOVA) models (log and non-log) were computed to examine costs from a societal perspective. All costs were calculated in 1999 US dollars. Study population: Outpatients with moderate to severe AD. Overall, 252 patients received randomised treatment, and 166 patients (placebo n = 76, memantine n = 90) formed the treated-per-protocol (TPP) subset for the health economic analyses, on which the main cost analysis was based. MAIN OUTCOME MEASURE: Resource Utilisation in Dementia (RUD) scale, measuring patient and caregiver resource utilisation, and various sources for cost calculations. RESULTS: Controlling for baseline differences between the groups, significantly less caregiver time was needed for patients receiving memantine than for those receiving placebo (difference 51.5 hours per month; 95% CI -95.27, -7.17; p = 0.02). Analysis of residential status also favoured memantine: time to institutionalisation (p = 0.052) and institutionalisation at week 28 (p = 0.04 with the chi-square test). Total costs from a societal perspective were lower in the memantine group (difference dollars US 1089.74/month [non-overlapping 95% CI for treatment difference -1954.90, -224.58]; p = 0.01). The main differences between the groups were total caregiver costs (dollars US-823.77/month; p = 0.03) and direct nonmedical costs (dollars US-430.84/month; p = 0.07) favouring memantine treatment. Patient direct medical costs were higher in the memantine group (p < 0.01), mainly due to the cost of memantine. CONCLUSION: Resource utilisation and total health costs were lower in the memantine group than the placebo group. The results suggest that memantine treatment of patients with moderate to severe AD is cost saving from a societal perspective.

Wimo A, Winblad B, Engedal K, Soininen H, Verhey F, Waldemar G, Wetterholm AL, Mastey V, Haglund A, Zhang R, Miceli R, Chin W, Subbiah P, Anonymous00005. · Department of Family Medicine, Umeå University, Umeå, Sweden. · Dement Geriatr Cogn Disord. · Pubmed #12457078 No free full text.

Abstract: 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.

Winblad B, Engedal K, Soininen H, Verhey F, Waldemar G, Wimo A, Wetterholm AL, Zhang R, Haglund A, Subbiah P, Anonymous00311. · Karolinska Institutet, Alzheimer's Disease Research Center, Division of Geriatric Medicine, Huddinge Hospital B, Stockholm, Sweden. · Neurology. · Pubmed #11502918 No free full text.

Abstract: OBJECTIVE: To evaluate the long-term clinical efficacy and safety of donepezil versus placebo over 1 year in patients with mild to moderate AD. METHODS: Patients (n = 286; mean age, 72.5 years) with possible or probable AD from five Northern European countries were randomized to receive either donepezil (n = 142; 5 mg/day for 28 days, followed by 10 mg/day) or placebo (n = 144) for 1 year. RESULTS: The study was completed by 66.9% of the donepezil- and 67.4% of the placebo-treated patients. The benefit of donepezil over placebo was demonstrated by the Gottfries-Bråne-Steen (a global assessment for rating dementia symptoms) total score at weeks 24, 36, and 52 (p < 0.05) and at the study end point (week 52, last observation carried forward; p = 0.054). Advantages of donepezil over placebo were also observed in cognition and activities of daily living (ADL) assessed by the Mini-Mental State Examination at weeks 24, 36, and 52, and the end point (p < 0.02) and by the Progressive Deterioration Scale at week 52 and the end point (p < 0.05). Adverse events (AE) were recorded for 81.7% of donepezil- and 75.7% of placebo-treated patients, with 7% of donepezil- and 6.3% of placebo-treated patients discontinuing because of AE. Treatment response to donepezil was not predicted by APOE genotype or sex in this population. CONCLUSION: As the first 1-year, multinational, double-blinded, placebo-controlled study of a cholinesterase inhibitor in AD, these data support donepezil as a well tolerated and effective long-term treatment for patients with AD, with benefits over placebo on global assessment, cognition, and ADL.

Wimo A, Johansson L, Jönsson L. · Institutionen för neurobiologi, vårdvetenskap och samhälle, KI-Alzheimer Disease Research Center, Karolinska institutet, Stockholm. · Lakartidningen. · Pubmed #19537500 No free full text.

This publication has no abstract.

Burns A, Bernabei R, Bullock R, Cruz Jentoft AJ, Frölich L, Hock C, Raivio M, Triau E, Vandewoude M, Wimo A, Came E, Van Baelen B, Hammond GL, van Oene JC, Schwalen S. · University of Manchester, Manchester, UK. · Lancet Neurol. · Pubmed #19042161 No free full text.

Abstract: BACKGROUND: The efficacy of galantamine has been shown in patients with mild, moderate, and advanced moderate Alzheimer's disease (AD). Here we report its efficacy in patients with severe AD. METHODS: Between December, 2003, and March, 2007, patients aged 84 (SD 6) years with severe AD (mini-mental state examination [MMSE] score 5-12 points), in a nursing home setting were randomly assigned to receive galantamine (n=207), titrated initially to 24 mg/day, or placebo (n=200). Co-primary efficacy measures for cognitive function and ability to undertake normal daily activities were the severe impairment battery (SIB) and the seven-item minimum data set-activities of daily living (MDS-ADL), respectively. Adverse events, vital signs, laboratory parameters, and electrocardiograms were monitored. This trial is registered with ClinicalTrials.gov, number NCT00216593. FINDINGS: 168 of 207 (81%) patients in the galantamine group and 161 of 200 (81%) in the placebo group completed the study. Mean SIB scores increased (improved) by 1.9 (95% CI -0.1 to 3.9) points with galantamine and decreased (worsened) by 3.0 (-5.6 to -0.5) points with placebo (between-group least squares mean difference 4.36, 1.3 to 7.5; p=0.006). Mean MDS-ADL self-performance score worsened by 1.2 (0.6 to 1.8) points and 1.6 (0.8 to 2.3) points, respectively (between-group least squares mean difference -0.41, -1.3 to 0.5; p=0.383). Nominally significant between-group differences in favour of galantamine occurred for the SIB domains of memory (p=0.006), praxis (p=0.010), and visuospatial ability (p=0.002), and for the MDS-ADL subitem locomotion on unit (p=0.021). 183 of 207 patients (88%) who received galantamine and 177 of 200 (89%) who received placebo had adverse events, which were mostly mild to moderate. Eight patients (4%) in the galantamine group and 21 patients (11%) in the placebo group died. ECG abnormalities were similar between the two groups. INTERPRETATION: Galantamine can be started and used safely in elderly patients with severe AD. Galantamine improved cognitive function but failed to significantly improve the co-primary parameter of overall activities of daily living.

Jedenius E, Wimo A, Strömqvist J, Andreasen N. · Alzheimer's Disease Research Centre, Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Stockholm, Sweden. · Scand J Prim Health Care. · Pubmed #18788054 links to  free full text

Abstract: OBJECTIVE: To meet diagnostic needs of dementia, a new care programme was implemented in the county of Kalmar, Sweden. The objective of the study was to analyse whether the programme could identify and diagnose the estimated number of new cases. METHODS: A long-term follow up study on all new patients referred to primary and specialist care between 1999 and 2005 for dementia evaluation. RESULTS; Based on epidemiological data, 153 new cases per year were expected. Using the programme, an average of 127 cases was identified in primary healthcare and 22 at specialist level. Although the number of false-negative cases is not known, it may be concluded that most of the new cases with dementia were identified. The proportion of cases identified doubled after implementing the programme. The programme was implemented within an unchanged budget. CONCLUSION: The programme may be of value for diagnosis and management of demented patients in primary healthcare.

Winblad B, Kawata AK, Beusterien KM, Thomas SK, Wimo A, Lane R, Fillit H, Blesa R. · Karolinska Institutet Alzheimer Research Center, Huddinge, Sweden. · Int J Geriatr Psychiatry. · Pubmed #17407176 No free full text.

Abstract: BACKGROUND: Family caregivers comprise a critical component in the care of Alzheimer's disease (AD) patients. Among their many tasks, caregivers are responsible for administering and managing medications. Effective interventions incorporate the needs of both the AD patient and the caregiver, and understanding treatment preferences may maximize intervention effectiveness. Transdermal patches may offer advantages over conventional oral formulations. METHODS: A 24-week randomized controlled trial compared the rivastigmine patch to the rivastigmine capsule and placebo in patients with probable AD. At baseline and Weeks 8 and 24, the AD Caregiver Preference Questionnaire (ADCPQ) was used to evaluate caregiver expectations, preferences and satisfaction with treatment. Double-dummy treatment blinding ensured that caregiver preference for the patch or capsule was not confounded by perceptions of efficacy or tolerability. Reasons for preference were also elicited. The analytic sample included caregivers who completed the ADCPQ at Weeks 8 and/or 24. RESULTS: One thousand and fifty-nine caregivers completed the ADCPQ. More than 70% of caregivers preferred the rivastigmine patch to the capsule. The patch was significantly preferred to the capsule with respect to ease of following the schedule and ease of use. Caregivers indicated greater satisfaction overall, greater satisfaction with administration, and less interference with daily life with the patch versus the capsule (all p<or=0.01). CONCLUSION: Caregivers of AD patients preferred the patch to the capsule for drug delivery. Preference for the rivastigmine patch could potentially lead to improved compliance and improved clinical benefits.

Jönsson L, Eriksdotter Jönhagen M, Kilander L, Soininen H, Hallikainen M, Waldemar G, Nygaard H, Andreasen N, Winblad B, Wimo A. · Division of Geriatric Epidemiology, the Neurotec Department, Karolinska Institutet, Stockholm, Sweden. · Int J Geriatr Psychiatry. · Pubmed #16676288 No free full text.

Abstract: BACKGROUND: Alzheimer's disease (AD), the most common cause of dementia, is a major cause of disability and care burden in the elderly. This study aims to estimate the costs of formal and informal care and identity determinants of care costs. MATERIALS AND METHODS: Two hundred and seventy-two (AD) patients and their caregivers were recruited among patients attending regular visits at six memory clinic in Sweden, Denmark, Norway and Finland. Patients with a diagnosis of AD and with an identifiable primary caregiver were eligible for inclusion. Data was collected by questionnaires at baseline, and at scheduled follow-up visits after 6 months and again after 12 months. Cognitive function was assessed with the Mini Mental State Examination (MMSE) and behavioural disturbances were measured using a brief version of the neuropsychiatric inventory (NPI). RESULTS: Total annual costs were on average 172,000 SEK, ranging from 60,700 SEK in mild dementia to 375,000 SEK in severe dementia. Costs for community care (special accommodation, home help, etc.) constituted about half of total costs of care and increase sharply with increasing cognitive impairment. Informal care costs, valued at the opportunity cost of the caregiver's time, make up about a third of total costs and also increased significantly with disease severity. Medical care costs (inpatient care, outpatient care, pharmaceuticals), on the other hand, were not significantly related to disease severity. Regression analysis confirmed a strong association between costs and cognitive function, between patients as well as within patients over time. There was also a significant influence on costs from behavioural disturbances. Sensitivity analysis showed that the method chosen to value informal care can have considerable impact on results. CONCLUSIONS: Costs of care in patient with AD are high and related to dementia severity as well as presence of behavioural disturbances. The cost estimates presented have implications for future economic evaluation of treatments for Alzheimer's disease.

Winblad B, Wimo A, Engedal K, Soininen H, Verhey F, Waldemar G, Wetterholm AL, Haglund A, Zhang R, Schindler R. · Karolinska University Hospital Huddinge, Stockholm, Sweden. · Dement Geriatr Cogn Disord. · Pubmed #16508298 No free full text.

Abstract: Delays in the diagnosis of Alzheimer's disease, and, therefore, delays in treatment, may have a detrimental effect on a patient's long-term well-being. This study assessed the effects of postponing donepezil treatment for 1 year by comparing patients treated continuously for 3 years with those who received placebo for 1 year followed by open-label donepezil for 2 years. Patients (n = 286) with possible or probable Alzheimer's disease (according to DSM-IV, NINCDS-ADRDA, and Mini-Mental State Examination criteria; see text) were randomized to receive donepezil (5 mg/day for 4 weeks, 10 mg/day thereafter) or placebo (delayed-start group) for 1 year. Of the 192 completers, 157 began a 2-year, open-label phase of donepezil treatment. Outcome measures were the Gottfries-Bråne-Steen scale, the Mini-Mental State Examination, the Global Deterioration Scale, the Progressive Deterioration Scale, the Neuropsychiatric Inventory, and safety (adverse events). Mixed regression analysis was used to compare changes between the groups over 3 years on the efficacy measures. There was a trend for patients receiving continuous therapy to have less global deterioration (Gottfries-Bråne-Steen scale) than those who had delayed treatment (p = 0.056). Small but statistically significant differences between the groups were observed for the secondary measures of cognitive function (Mini-Mental State Examination; p = 0.004) and cognitive and functional abilities (Global Deterioration Scale; p = 0.0231) in favor of continuous donepezil therapy. Over 90% of the patients in both cohorts experienced one treatment-emergent adverse event; most were considered mild or moderate. In conclusion, patients in whom the start of treatment is delayed may demonstrate slightly reduced benefits as compared with those seen in patients starting donepezil therapy early in the course of Alzheimer's disease. These data support the long-term efficacy and safety of donepezil.

Jönsson L, Andreasen N, Kilander L, Soininen H, Waldemar G, Nygaard H, Winblad B, Jönhagen ME, Hallikainen M, Wimo A. · Neurotec, Section for Geriatric Epidemiology, Karolinska Institutet, Stockholm, Sweden. · Alzheimer Dis Assoc Disord. · Pubmed #16493236 No free full text.

Abstract: This study aims to compare patient- and proxy-rated utilities and health-related quality of life from individuals in different stages of Alzheimer disease (AD). Two hundred seventy-two patients and their primary caregivers were enrolled in a prospective observational study and underwent three consecutive interviews, 6 months apart. Average Mini-Mental State Examination (MMSE) scores were 19.3, 18.0, and 16.4 at the three interviews; scores ranged from 0 to 30. Using the EuroQoL EQ-5D instrument, patient-rated health utilities were on average 0.833 with little variation across MMSE-based severity levels. Proxy-rated health utilities were 0.69 (MMSE >25), 0.64 (MMSE 21-25), 0.50 (MMSE 15-20), 0.49 (MMSE 10-14), and 0.33 (MMSE <10). Proxy-rated utilities, as well as changes in utilities over time, were significantly related to MMSE scores and inversely related to scores on a brief version of the neuropsychiatric inventory (NPI) and institutionalization. Utilities were highly correlated with the disease-specific quality of life instrument QoL-AD. The study shows that the EuroQoL can be used to rate utilities in Alzheimer disease, but there are important differences between patient- and proxy-ratings.

Garfield FB, Getsios D, Caro JJ, Wimo A, Winblad B. · Caro Research Institute, Concord, Massachusetts 01742, USA. · Pharmacoeconomics. · Pubmed #12141890 No free full text.

Abstract: BACKGROUND: Like other developed countries with aging populations, Sweden is expecting large increases in the prevalence of Alzheimer's disease and corresponding escalations in the cost of care for patients with this disease. Galantamine, a new acetylcholinesterase inhibitor and nicotinic modulator, has proved effective in managing patients with Alzheimer's disease in clinical trials. OBJECTIVE: To estimate the long-term health and economic impact of galantamine from the perspective of the public health payer in Sweden. DESIGN AND SETTING: The Assessment of Health Economics in Alzheimer's Disease (AHEAD) model compares galantamine treatment with no pharmacologic treatment. It consists of a module based on trial data followed by a projection module that uses the trial results to predict the time until patients require full-time care (FTC) or until their death. Forecasts were made for up to 10 years. The model was customised to Sweden by using Swedish resource use profiles obtained from the literature. RESULTS: Galantamine is predicted to reduce the time patients require FTC by almost 10%. Approximately 5.6 patients with mild-to-moderate disease would need to be treated to avoid one year of FTC. This would result in savings averaging 27 436 Swedish kronas (SEK) [3131 euros (EUR)] per patient over 10 years (1998 values). To avoid one year of FTC, 3.9 patients with moderate disease would need to be treated, with savings averaging SEK49 019 (EUR 5594) per patient over 10.5 years. Sensitivity analyses of key parameters, such as proportion of patients needing FTC treated in the community, cost of care in an institution, cost of FTC care in the community, the price of galantamine, and the discount rate, found savings with galantamine would occur under most circumstances. CONCLUSION: Galantamine can increase the time before patients require FTC, and may also lead to savings as treatment costs are offset by reductions in other healthcare expenditures and the costs associated with FTC.

Wimo A, von Strauss E, Nordberg G, Sassi F, Johansson L. · HC Bergsjö, Box 16, S-820 70 Bergsjö, Sweden. · Health Policy. · Pubmed #12098519 No free full text.

Abstract: The purpose of this paper was to explore the time spent on caring by families of persons with dementia in Sweden. As part of a European Commission project, interviews were carried out on a sample of 92 carers, caring for persons with dementia. The interviews focused on time spent on caring, IADL, ADL and surveillance, as well as formal support received and used. Informal care, measured as hours spent caring, was about 8.5 times greater than formal services (299 and 35 h per month, respectively). Approximately 50% of the total informal care consisted of time spent on surveillance (day and night). Formal care input and informal support, in terms of ADL increased with dementia severity. A regression analysis showed that dementia severity, behavioural disturbances and coping were associated with the amount of informal care. This study gives some new perspectives on informal care giving for persons with dementia and support strategies in general. Some carers do carry a very heavy 24 h responsibility. This aspect of caring must be addressed by the development of well-targeted respite and relief support programmes.

Jönsson L, Lindgren P, Wimo A, Jönsson B, Winblad B. · Centre for Health Economics, Stockholm School of Economics, Sweden. · Clin Ther. · Pubmed #10463520 No free full text.

Abstract: This study compared the cost-effectiveness of donepezil, a new cholinesterase inhibitor indicated for the treatment of mild-to-moderate probable Alzheimer's disease (AD), with no treatment. A Markov state transition model was employed to simulate treatment costs based on Swedish epidemiologic data. The Markov states used in the model were defined according to cognitive function, as assessed by the Mini-Mental State Examination. Data on costs and baseline transition probabilities were taken from the Kungsholmen Project, an observational, population-based study of persons aged >75 years in Sweden. Data on the treatment effect were taken from a clinical trial comparing donepezil to placebo over 24 weeks and were applied to the baseline transition probabilities to assess the effect of treating the clinical manifestations of AD in Swedish patients. Also, a within-trial analysis was performed for comparison, using transition probabilities taken from the clinical study. Both models were run for 5 years in half-year cycles, and both demonstrated various degrees of cost savings and improved effectiveness, as measured by increased time in nonsevere disease states. Thus donepezil had superior cost-effectiveness compared with no treatment.

Jönsson L, Jönsson B, Wimo A, Whitehouse P, Winblad B. · Division of Geriatric Medicine, NEUROTEC, Karolinska Institute, Sweden. · Alzheimer Dis Assoc Disord. · Pubmed #10994654 No free full text.

Abstract: The Second International Pharmacoeconomic Conference on Alzheimer's Disease was held in Stockholm, Sweden, on April 4, 2000. The presentations focused on the role of cognition in pharmacoeconomic evaluations, the costs and consequences of behavioral disturbances, quality of life, disease progression models, and methods for valuing informal care. The results from individual studies will be published separately. Cognition has been used as the sole measure of disease severity in economic evaluations in dementia. However, behavioral disturbances are an important determinant of both cost and quality of life and should also be considered when appraising the effect of treatment. Quality-of-life assessment constitutes a single measure of the total impact of the disease, as well as a way of quantifying the benefits of treatment with antidementia drugs so that they can be compared with interventions in other disease areas. Measuring the quality of life of patients with dementia is associated with methodologic difficulties related to the difficulties for some patients in completing usual assessment processes. Disease progression models may be helpful in extrapolating the results from clinical trials to longer time periods and more representative populations. Modeling is an unavoidable part of the economic evaluation of antidementia drugs, and efforts should be made to increase transparency and comparability among models. Informal care constitutes a large percentage of the total care for patients with dementia, and the valuation of these services has a large impact on the results of pharmacoeconomic evaluations. Difficulties lie in quantifying the time spent on caring for the elderly and in attaching the correct price to each unit of time. The contingent valuation method is an alternative way of valuing informal care that so far has not been used in the field of dementia.