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Guideline Alzheimer's Disease International and International Working Group for Harmonization of Dementia Drug Guidelines for research involving human subjects with dementia. 1999
Brodaty H, Dresser R, Eisner M, Erkunjuntti T, Gauthier S, Graham N, Jonker C, Sachs G, Whitehouse P. · No affiliation provided · Alzheimer Dis Assoc Disord. · Pubmed #10372949 No free full text.
This publication has no abstract.
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Review Outcome measures for the study of activities of daily living in vascular dementia. 1999
Gauthier S, Rockwood K, Gélinas I, Sykes L, Teunisse S, Orgogozo JM, Erkinjuntti T, Erzigkeit H, Gleeson M, Kittner B, Pontecorvo M, Feldman H, Whitehouse P. · McGill Centre for Studies in Aging, Verdun, Quebec, Canada. · Alzheimer Dis Assoc Disord. · Pubmed #10609694 No free full text.
Abstract: Decline in functional abilities is a major component of the dementia syndrome. The definition of dementia in the International Classification of Diseases (10th rev.) requires a cognitive impairment sufficient to impair personal activities of daily living (ADL). The Diagnostic and Statistical Manual of Mental Disorders (4th ed.) also requires cognitive deficits sufficiently severe to cause impairment in occupational or social functioning and must represent a decline from a higher level of functioning. However, the term disability is more appropriate than impairment to describe a loss in activities, as opposed to a loss of elementary functions, and is consistent with World Health Organization definitions of impairment, disability, and handicap. There is no doubt that ADL outcomes are required in therapeutic drug studies on vascular dementia, and there is a good rationale and some evidence for the use of ADL scales developed for therapeutic research in Alzheimer disease, favoring scales devoid of items sensitive to physical disabilities. Similarly, ADL-related clinical milestones could be used for longer-term studies aiming predominantly at slowing progression of disease in both early and later stages of dementia. Slower decline in ADL and delay in reaching ADL-related clinical milestones should be considered as valid outcomes by regulatory bodies in the process of dementia drug approval.
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Clinical Conference Treatment of agitation in AD: a randomized, placebo-controlled clinical trial. 2000
Teri L, Logsdon RG, Peskind E, Raskind M, Weiner MF, Tractenberg RE, Foster NL, Schneider LS, Sano M, Whitehouse P, Tariot P, Mellow AM, Auchus AP, Grundman M, Thomas RG, Schafer K, Thal LJ, Anonymous00040. · University of Washington, Department of Psychosocial and Community Health, Seattle 98195-7263, USA. · Neurology. · Pubmed #11087767 No free full text.
Abstract: BACKGROUND: Treatment of agitation is a crucial problem in the care of patients with AD. Although antipsychotic and antidepressant medications and behavior management techniques (BMT) have each been used to treat agitation, clinical trials of these treatments have been characterized by small sample sizes and uncontrolled treatment designs. OBJECTIVE: To compare haloperidol, trazodone, and BMT with placebo in the treatment of agitation in AD outpatients. METHODS: A total of 149 patients with AD and their caregivers participated in a randomized, placebo-controlled, multicenter trial. Blind assessment was conducted at baseline and after 16 weeks of treatment. The three active treatments were haloperidol, trazodone, and BMT. The Alzheimer's Disease Cooperative Study Clinical Global Impression of Change was the primary outcome measure. Secondary outcomes included patient agitation, cognition, and function, and caregiver burden. RESULTS: Thirty-four percent of subjects improved relative to baseline. No significant differences on outcome were obtained between haloperidol (mean dose, 1.8 mg/d), trazodone (mean dose, 200 mg/d), BMT, or placebo. Significantly fewer adverse events of bradykinesia and parkinsonian gait were evident in the BMT arm. No other significant difference in adverse events was seen. Symptoms did not respond differentially to the different treatments. CONCLUSIONS: Comparable modest reductions in agitation occurred in patients receiving haloperidol, trazodone, BMT, and placebo. More effective pharmacologic, nonpharmacologic, and combination treatments are needed.
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Article Genetic susceptibility testing versus family history-based risk assessment: Impact on perceived risk of Alzheimer disease. 2005
LaRusse S, Roberts JS, Marteau TM, Katzen H, Linnenbringer EL, Barber M, Whitehouse P, Quaid K, Brown T, Green RC, Relkin NR. · Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA. · Genet Med. · Pubmed #15654228 No free full text.
Abstract: PURPOSE: We examined how an Alzheimer disease (AD) family history assessment as compared to a risk assessment incorporating the absence of a disease-associated susceptibility allele affected risk perception among adult children with a family history of AD. METHODS: The REVEAL study is a clinical trial in which adult children of patients with AD were randomized to receive a risk assessment based upon family history alone or family history plus apolipoprotein E (APOE) disclosure. In this analysis, two subsets of women were identified, each of whom received identical 29% lifetime risk estimates of developing AD. One group received a risk estimate that incorporated APOE epsilon4-negative genetic test results (Genotype Group, n = 30), whereas the other received a risk estimate based on family history and gender (Family History Group, n = 36). Six weeks after risk disclosure, we surveyed participants regarding the impact of the risk assessment on their perceptions of AD risk. RESULTS: 73% of the Genotype Group judged their risk to be lower compared to 25% of the Family History Group (P < 0.0001). 67% of the Genotype Group reported lower anxiety about AD, versus 26% of the Family History Group (P < 0.01). 80% of the Genotype Group indicated that the risk information had a positive impact, versus 36% of the Family History Group (P < 0.001). The Genotype Group was less likely to believe that they would develop AD (13% vs. 36%, P < 0.05) and was more likely to report that the risk assessment removed uncertainty about their chances of developing AD (63% vs. 9%, P < 0.0001). CONCLUSIONS: These data suggest that risk estimates incorporating negative genetic test results affect perceptions of disease susceptibility more strongly than identical estimates based on family history alone.
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Article Estimating risk curves for first-degree relatives of patients with Alzheimer's disease: the REVEAL study. 2004
Cupples LA, Farrer LA, Sadovnick AD, Relkin N, Whitehouse P, Green RC. · Departments of Biostatistics and Epidemiology, Boston University School of Public Health, 715 Albany Street, Boston, MA 02118, USA. · Genet Med. · Pubmed #15266206 No free full text.
Abstract: PURPOSE: The REVEAL study is a randomized, controlled study of the psychological and behavioral impact of APOE disclosure in a risk assessment protocol provided to first degree relatives of patients with Alzheimer's disease. The protocol presents risk information as cumulative incidence curves. This article describes how these curves were estimated. METHODS: Curves were calculated using Bayes' rule to compute the posterior survival curves incorporating APOE information. RESULTS: A combination of survival data from the MIRAGE study and gender- and age-specific APOE odds ratios were used to create risk curves for males and females within each of the 6 APOE genotypes. CONCLUSION: Utilizing comparative genotype relative risk information and survival data from family studies, estimates of gender-, age-, and genotype-specific risk can be generated for use in a risk assessment research study that features genotype disclosure.
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Article Breaking the diagnosis of dementia. 2004
Whitehouse P, Frisoni GB, Post S. · No affiliation provided · Lancet Neurol. · Pubmed #14747005 No free full text.
This publication has no abstract.
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Minor Second International Pharmacoeconomic Conference on Alzheimer' s Disease. 2000
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.
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