Alzheimer Disease: Whitehouse PJ

Whitehouse PJ. · No affiliation provided · Alzheimer Dis Assoc Disord. · Pubmed #11403331 No free full text.

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Hinze SW, Gaines AD, Lerner AJ, Whitehouse PJ. · No affiliation provided · Alzheimer Dis Assoc Disord. · Pubmed #10609665 No free full text.

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Ballenger JF, Nelson JL, Whitehouse PJ. · No affiliation provided · Alzheimer Dis Assoc Disord. · Pubmed #10485570 No free full text.

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Whitehouse PJ, Arizaga R, Brodaty H, Gauthier S, Graham N, Green RC, Homma A, Mangone C, Senanarong V, Xu XH. · No affiliation provided · Alzheimer Dis Assoc Disord. · Pubmed #10485568 No free full text.

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Post SG, Whitehouse PJ, Nelson JL, Sachs GA. · No affiliation provided · Alzheimer Dis Assoc Disord. · Pubmed #10372947 No free full text.

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Whitehouse PJ, Waller S. · Department of Neurology, Case Western Reserve University, Cleveland, Ohio, USA. · Neurotherapeutics. · Pubmed #17599723 No free full text.

Abstract: Understanding why we produce labels for neuropsychiatric conditions, such as Alzheimer's disease (AD), and how we use those words to tell stories about our brain, as well as which groups control such diagnostic discourse, is important to a wise understanding of our cognitive abilities, their limitations, and even our very human nature. Here, we explore the history and current focus of a newly emerging field called neuroethics and explore its relationship (or lack thereof) to a newly created clinical syndrome called involuntary emotional expressive disorder (IEED). The main argument concerns the lack of neuroethical discussion of issues pertinent to social influences on disease and the construction of professional specialization. We are critical of the processes associated with the creation of both the field and the syndrome, and express concern about their eventual outcomes. The interaction of social, political, and business institutions, the inherent interests of the advancement of larger research projects (and the individuals that compose them), their potential for profit, and other incentives to enhance marketability and public attention toward certain research programs will be examined as we discuss the development of the field of neuroethics. Similarly, we argue that these social factors and forces are instrumental in the development of IEED as a recognizable category and condition. Our critique is guided by the hope that through such analyses we can improve our understanding of how we go about our academic activities in cognitive neuroscience and also improve our efforts to help people suffering from neuropsychiatric conditions, such as dementia.

Whitehouse PJ. · University Memory and Aging Center, University Hospitals of Cleveland/Case Western Reserve University, Cleveland, OH 44120, USA. · J Altern Complement Med. · Pubmed #17480133 No free full text.

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Whitehouse PJ. · Department of Neurology, Case Western Reserve University, Cleveland, OH 44120, USA. · Alzheimer Dis Assoc Disord. · Pubmed #17132959 No free full text.

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Whitehouse PJ. · No affiliation provided · Prog Brain Res. · Pubmed #14650925 No free full text.

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Barber M, Whitehouse PJ. · University Memory and Aging Center, Case Western Reserve University, Cleveland, OH 44120-1013, USA. · Lancet Neurol. · Pubmed #12849539 No free full text.

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Szatmari SZ, Whitehouse PJ. · 4300, Targu Mures, str. Gral I., Dumitrache 22, Romania. · Cochrane Database Syst Rev. · Pubmed #12535455 No free full text.

Abstract: BACKGROUND: Vinpocetine is a synthetic ethyl ester of apovincamine, a vinca alkaloid obtained from the leaves of the Lesser Periwinkle (Vinca minor) and discovered in the late 1960s. Although used in human treatment for over twenty years, it has not been approved by any regulatory body for the treatment of cognitive impairment. Basic sciences studies have been used to claim a variety of potentially important effects in the brain. However, despite these many proposed mechanisms and targets, the relevance of this basic science to clinical studies is unclear. OBJECTIVES: To assess the efficacy and safety of vinpocetine in the treatment of patients with cognitive impairment due to vascular disease, Alzheimer's disease, mixed (vascular and Alzheimer's disease) and other dementias. SEARCH STRATEGY: The Cochrane Dementia & Cognitive Improvement Group's Specialized Register was searched using the terms vinpocetin*, cavinton, kavinton, Rgh-4405, Tcv-3B, "ethyl apovincaminate", vinRx, periwinkle, "myrtle vincapervinc" and cezayirmeneksesi. The manufacturers of vinpocetine were asked for information on trials of vinpocetine for dementia. In addition we tried to collect articles not listed in MEDLINE or other sources on the Internet (e.g. articles in Hungarian and Romanian). SELECTION CRITERIA: All human, unconfounded, double-blind, randomized trials in which treatment with vinpocetine was administered for more than a day and compared to control in patients with vascular dementia, Alzheimer's dementia or mixed Alzheimer's and vascular dementia and other dementias. Non-randomized trials were excluded. DATA COLLECTION AND ANALYSIS: Data were independently extracted by the two reviewers (SzSz and PW) and cross-checked. Data from "washout" periods were not used for the analysis. For continuous or ordinal variables, such as cognitive test results, the main outcomes of interest were the change in score from baseline. The categorical outcome of global impression was transformed to binary data (improved or not improved) as was the occurrence of adverse effects; here the endpoint itself was of interest the Peto method of the "typical odds ratio" was used. A test for heterogeneity of treatment effects between the trials was made if appropriate. Data synthesis and analysis were performed using the Cochrane Review Manager software (RevMan version 4.1). MAIN RESULTS: All identified studies were performed before the 1990s and used various terms and criteria for cognitive decline and dementia. The three studies included in the review involved a total of 583 people with dementia treated with vinpocetine or placebo. The reports of these studies did not make possible any differentiation of effects for degenerative or vascular dementia. The results show benefit associated with treatment with vinpocetine 30mg/day and 60 mg/day compared with placebo, but the number of patients treated for 6 months or more was small. Only one study extended treatment to one year. Adverse effects were inconsistently reported and without regard for relationship to dose. The available data do not demonstrate many problems of adverse effects but intention-to-treat data were not available for any of the trials. REVIEWER'S CONCLUSIONS: Although the basic science is interesting, the evidence for beneficial effect of vinpocetine on patients with dementia is inconclusive and does not support clinical use. The drug seems to have few adverse effects at the doses used in the studies. Large studies evaluating the use of vinpocetine for people suffering from well defined types of cognitive impairment are needed to explore possible efficacy of this treatment.

Whitehouse PJ. · University Alzheimer Center, Cleveland, OH 44120-1013, USA. · Eur Arch Psychiatry Clin Neurosci. · Pubmed #10654099 No free full text.

Abstract: As we look to a world where more individuals will suffer from dementia, it is important to reflect on our past accomplishments as we work to create a better future. Attempts to develop better medications for Alzheimer's disease focus on symptomatic treatments for both cognitive and behavioral symptoms. Some progress has been made in the areas through use of cholinesterase inhibitors and novel neuroleptics. Quality of life is a central concept to improving our interventions and to developing more effective treatments based on our understanding of pathogenesis. In the past, almost hundred years since the pioneering work in Emil Kraepelin's laboratory that we are celebrating in this series of papers, we have come far but we have further to go.

Kawas CH, Clark CM, Farlow MR, Knopman DS, Marson D, Morris JC, Thal LJ, Whitehouse PJ. · Department of Neurology and Alzheimer's Disease Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224, USA. · Alzheimer Dis Assoc Disord. · Pubmed #10485569 No free full text.

Abstract: During the past 10 years, there has been a rapidly growing number of pharmaceutical industry-sponsored drug trials for treatment of Alzheimer disease (AD) and other neurodegenerative diseases. As public awareness and concerns about AD have grown, so has interest in developing drug therapies for retarding symptom progression, delaying onset, and ultimately curing the disease. Ethical debate on the use of placebo control trials in AD research has come of age in the United States with the availability of treatments approved by the Food and Drug Administration. The experts and the public agree that more effective therapies are necessary, and new therapeutic options are being developed as rapidly as possible. The arguments on each side of the debate are provocative and important but do not provide unequivocal justification for either the abandonment or the maintenance of placebo-controlled trials in all AD research. Clinical trials differ with respect to scientific and practical goals, and these factors inherently affect the ethical priorities of each study. We present these contrasting points of view to delineate some of the issues rather than to make specific recommendations other than to urge that all clinical trials in AD should be designed with careful consideration of the ethical issues surrounding the use of placebo controls. As new and more effective treatments emerge, the ethical framework for placebo use in AD studies will require frequent re-examination. To make wise choices, patients, caregivers, physicians, and ethicists (among others) must have a voice in this continuing discussion.

Roberts JS, Barber M, Brown TM, Cupples LA, Farrer LA, LaRusse SA, Post SG, Quaid KA, Ravdin LD, Relkin NR, Sadovnick AD, Whitehouse PJ, Woodard JL, Green RC. · Departments of Neurology and Medicine (Genetics Program), Boston University School of Medicine, 715 Albany Street B-7800, Boston, MA 02118, USA. · Genet Med. · Pubmed #15266207 No free full text.

Abstract: PURPOSE: Alzheimer's disease, for which one form of the apolipoprotein E (APOE) genotype is a risk factor, provides a paradigm in which to examine response to susceptibility testing for common, complex diseases. This study's main purposes were to estimate interest in such testing and to examine demographic predictors of study participation. METHODS: In this 3-site, randomized clinical trial (RCT), the intervention was a risk assessment program wherein genetic counselors educated adult children of AD patients about lifetime risk of disease based on their gender, family history, and APOE genotype. Two groups of participants were followed from initial contact to RCT enrollment: those who were systematically contacted through research registries, and those who were self-referred. RESULTS: Of 196 systematically contacted participants, 47, or 24%, progressed from initial contact to RCT enrollment. These participants were more likely to be below age 60 (adjusted OR = 3.83, P < 0.01) and college educated (adjusted OR = 3.48, P < 0.01). Of 179 self-referred participants, 115, or 64%, progressed from initial contact to RCT enrollment. Most self-referred participants had a college education and were female (79%). CONCLUSIONS: In the first RCT to examine genetic susceptibility testing for AD, uptake rates were sufficiently high to merit concern that future test demand may strain available education and counseling resources. Findings suggest that susceptibility testing for AD may be of particular interest to women, college educated persons, and persons below age 60.

Roberts JS, LaRusse SA, Katzen H, Whitehouse PJ, Barber M, Post SG, Relkin N, Quaid K, Pietrzak RH, Cupples LA, Farrer LA, Brown T, Green RC. · Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA. · Alzheimer Dis Assoc Disord. · Pubmed #12794385 No free full text.

Abstract: Advances in genetic research have provided a basis for susceptibility testing for Alzheimer disease (AD). Prior surveys have examined attitudes toward genetic testing for AD in hypothetical scenarios, but it is unclear what reasons would motivate people to seek testing in real-life situations. This study presents data from the first randomized trial to evaluate genetic susceptibility testing for asymptomatic adult children of people with AD. We examined (1) reasons endorsed as motivations for seeking testing, (2) demographic characteristics associated with these reasons, and (3) how these reasons related to the eventual decision to pursue testing. Eligible participants were 206 adult children of people with AD (mean age 53 years; 72% female; 93% white), 77.7% of whom (n = 160) went on to seek testing. Participants endorsed numerous reasons for seeking susceptibility testing (mean 7.2), encompassing a range of motivations. The most commonly endorsed reasons were as follows: (1) to contribute to research (93.9%), (2) to arrange personal affairs (87.4%), and (3) the hope that effective treatment will be developed (86.8%). Women strongly endorsed more reasons for seeking testing than men (p < 0.05). The best predictor of actual pursuit of testing was strong endorsement of the need to prepare family members for AD (odds ratio = 3.3, p < 0.01). Findings suggest that genetic susceptibility testing is of interest to individuals at risk for AD for a variety of reasons, even in the relative absence of available treatments.

Whitehouse PJ, George D. · Case Western Reserve University, Fairhill Center, Cleveland, OH 44120, USA. · Lancet. · Pubmed #19350706 No free full text.

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Whitehouse PJ. · University Neurology Institute, Case Western Reserve University, Cleveland, OH, USA. · J Alzheimers Dis. · Pubmed #18567175 No free full text.

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Christensen KD, Roberts JS, Royal CD, Fasaye GA, Obisesan T, Cupples LA, Whitehouse PJ, Butson MB, Linnenbringer E, Relkin NR, Farrer L, Cook-Deegan R, Green RC. · Department of Health Behavior and Health Education, University of Michigan School of Public Health, Ann Arbor, Michigan 48109-0471, USA. · Genet Med. · Pubmed #18344711 links to  free full text

Abstract: PURPOSE: To describe how investigators in a multisite randomized clinical trial addressed scientific and ethical issues involved in creating risk models based on genetic testing for African American participants. METHODS: The following informed our decision whether to stratify risk assessment by ethnicity: evaluation of epidemiological data, appraisal of benefits and risks of incorporating ethnicity into calculations, and feasibility of creating ethnicity-specific risk curves. Once the decision was made, risk curves were created based on data from a large, diverse study of first-degree relatives of patients with Alzheimer disease. RESULTS: Review of epidemiological data suggested notable differences in risk between African Americans and whites and that Apolipoprotein E genotype predicts risk in both groups. Discussions about the benefits and risks of stratified risk assessments reached consensus that estimates based on data from whites should not preclude enrolling African Americans, but population-specific risk curves should be created if feasible. Risk models specific to ethnicity, gender, and Apolipoprotein E genotype were subsequently developed for the randomized clinical trial that oversampled African Americans. CONCLUSION: The Risk Evaluation and Education for Alzheimer Disease study provides an instructive example of a process to develop risk assessment protocols that are sensitive to the implications of genetic testing for multiple ethnic groups with differing levels of risk.

Whitehouse PJ. · Case Western Reserve University School of Medicine, University Foley Elderhealth Center, 12200 Fairhill Rd, Cleveland, OH 44120, USA. · Cult Med Psychiatry. · Pubmed #18181012 No free full text.

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Whitehouse PJ. · Case Western Reserve University, University Memory and Aging Center, Integrative Studies, 12200 Fairhill Road, Room C357, Cleveland, OH 44120, USA. · Nat Clin Pract Neurol. · Pubmed #17279077 No free full text.

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Eckert SL, Katzen H, Roberts JS, Barber M, Ravdin LD, Relkin NR, Whitehouse PJ, Green RC. · Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA. · Genet Med. · Pubmed #17172937 No free full text.

Abstract: PURPOSE: To determine whether individuals recall their apolipoprotein E genotype and numeric lifetime risk estimates after undergoing a risk assessment for Alzheimer's disease. METHODS: One-hundred and four participants underwent Alzheimer's disease risk assessment that included disclosure of apolipoprotein E genotype and a numeric lifetime risk estimate. RESULTS: At six weeks and one year post-disclosure, 59% and 48% of participants, respectively, recalled their lifetime risk estimate, and 69% and 63% recalled their apolipoprotein E genotype. Participants were more likely to remember their genotype than numeric lifetime risk estimate at one year (P < 0.05). Apolipoprotein E epsilon4-positive participants had better recall of their genotype at both time points (P < 0.05). Participants were more likely to recall whether they carried the "risk-enhancing form of apolipoprotein E" than their specific genotype (P < 0.05). CONCLUSIONS: These data suggest that apolipoprotein E genotype, especially the presence of an epsilon4 allele, is more memorable than a numeric risk estimate for Alzheimer's disease. Participants recalled genotype information in a more simplified, binary form. Health professionals testing for complex disorders such as Alzheimer's disease must find an appropriate balance between communicating risk in an understandable format and addressing the probabilistic nature of the information.

Whitehouse PJ, Rajcan JL, Sami SA, Patterson MB, Smyth KA, Edland SD, George DR. · University Memory and Aging Center, University Hospitals of Cleveland, Case Western Reserve University, Cleveland, OH 44120-1013, USA. · Alzheimer Dis Assoc Disord. · Pubmed #17135813 No free full text.

Abstract: Both psychosocial and biologic interventions may delay or prevent Alzheimer disease. Staying mentally active may help older people maintain their cognitive abilities. In the Alzheimer Disease Cooperative Study Prevention Instrument Project a book club was introduced as a recruitment and retention device. A 3-arm study was designed and included: a nonrandomized, self-selected group (n=211) who chose not to participate in the book club, and 2 groups randomly assigned to receive 2 books per year in individual self-improvement (n=210) or community involvement (n=207) categories. Participants reported their reactions to the selections and other reading behaviors. Results from the first 2 years revealed that most book club participants agreed with Likert-type statements indicating the readings were enjoyable (P<0.001), had an impact on their thinking (P=0.01), and were shared by them with others (P=0.002). Respondents in the community involvement group agreed more strongly with these statements than those in the self-improvement category. Comments from participants in response to open-ended questions in the reader survey revealed such themes as developing plans for successful aging and reflecting on attitudes and behaviors in their own lives. Further longitudinal analyses are planned to determine whether the book club influenced retention and whether participation was associated with slowing cognitive decline.

Sano M, Zhu CW, Whitehouse PJ, Edland S, Jin S, Ernstrom K, Thomas RG, Thal LJ, Ferris SH, Anonymous00342. · Mount Sinai School of Medicine, James J Peters VAMC, Bronx, NY 10468, USA. · Alzheimer Dis Assoc Disord. · Pubmed #17135812 No free full text.

Abstract: BACKGROUND: The Prevention Instrument project of the Alzheimer's Disease Cooperative Study (ADCS) seeks to develop instruments to assess treatment efficacy including potential economic benefit. The Resource Use Inventory (RUI) is an instrument that has been used to capture resource utilization and costs in populations with Alzheimer disease (AD). However, resource utilization and costs for healthy, cognitively intact elderly as they begin to demonstrate cognitive deterioration are not well understood. In addition, the loss that relates to the subjects' own time as they transition through cognitive impairment is not well documented. OBJECTIVES: To evaluate the utility of the RUI in a sample of cognitively intact elderly individuals living in the community and enrolled in AD prevention trials. METHODS: The RUI was administered to 644 subjects and their study partners either at home or in the clinic. For half of each sample, 3-month retesting was carried out. The RUI consisted of 9 questions. The first part of the RUI captured subjects' use of direct medical care (eg, hospitalizations) and nonmedical care (eg, home health aides). The second part of the RUI captured the time caregivers spend providing care to the subjects. The third part of the RUI captured subjects' participation in volunteer work and employment. The assessment interval for each question was the past 3 months. RESULTS: The percentage of RUI forms returned incomplete or inaccurate for both in-clinic and at-home groups was extremely low. There were no differences in utilization rates between in-clinic and at-home group for all items in the RUI. Except for use of outpatient procedures, tests, or treatments, there were no differences in utilization rates between subjects who filled out the RUI with the help of their study partners or by themselves. Items in the RUI were sensitive to subjects' cognitive and functional status and demographic characteristics. CONCLUSIONS: Home-based completion of the RUI by participants in an AD prevention study is feasible, and seems to provide data that are reliable and valid. The instrument will be useful for tracking resource and time use through transition from healthy to cognitive impairment.

Patterson MB, Whitehouse PJ, Edland SD, Sami SA, Sano M, Smyth K, Weiner MF, Anonymous00341. · Case Western Reserve University, Cleveland, OH, USA. · Alzheimer Dis Assoc Disord. · Pubmed #17135811 No free full text.

Abstract: Information about quality of life (QOL) is valuable in evaluating pharmaceutical agents but it is not adequately assessed in many dementia drug trials. In prevention trials, following participants to conversion to AD requires QOL scales appropriate for both normal and cognitively impaired individuals. Our objective was to evaluate the utility of several scales for subject or informant QOL assessment: Quality of Life-AD; Quality of Life Activity Inventory; SF-36; SF-12 (a shortened version of the SF-36); and Satisfaction with Life Scale. Measurements were collected from 644 subject-study partner pairs, half of whom completed the instruments at the clinic and half at home. Three-month test-retest data were collected. Scales administered at home or in clinic did not differ significantly. Subject self-ratings showed a wide range for all scales. Test-retest intraclass coefficients ranged from 0.67 to 0.77. Moderately high interscale associations suggest that the scales are measuring common aspects of QOL but are not equivalent. Furthermore, they differed with respect to associations with demographic variables and QOL determinants. We conclude that the QOL scores at baseline show sufficient range and reliability to suggest they will have utility in tracking QOL through conversion to dementia.

Ferris SH, Aisen PS, Cummings J, Galasko D, Salmon DP, Schneider L, Sano M, Whitehouse PJ, Edland S, Thal LJ, Anonymous00336. · Alzheimer's Disease Center, New York University School of Medicine, New York, NY 10016, USA. · Alzheimer Dis Assoc Disord. · Pubmed #17135805 No free full text.

Abstract: One objective of the Alzheimer's Disease Cooperative Study (ADCS) is to develop new or improved instruments and assessment methods for evaluating treatment efficacy in Alzheimer disease (AD) clinical trials. The ADCS Instrument Committee has previously helped to define the state of the art in assessment for AD and Mild Cognitive Impairment clinical trials. We are now entering an exciting era of primary prevention trials to evaluate promising treatments that may delay disease onset and there is a need to develop appropriate instruments for these trials. The ADCS instrument committee has undertaken a project to develop instruments for prevention studies that assess domains known to be important in AD. Prevention trials are long and require large numbers of subjects, making them costly and requiring a high burden of participation for subjects. The current study focused on developing instruments that can be completed at home and in the clinic. The instruments are being evaluated in a cohort of nondemented elderly participating in a 4-year longitudinal study that simulates the design of a primary prevention trial. This report describes the design, baseline characteristics, and some longitudinal outcomes of the study cohort through the completion of the first 2 years of follow-up. We also describe the assessment domains to be measured with our new experimental instruments. This study recruited 644 subjects, 75 years of age and older. Participation in a "book club" that provided free books of interest to elders was offered as a recruitment incentive. Approximately 23% had some mild cognitive symptoms consistent with a Clinical Dementia Rating of 0.5. All subjects received a standardized in-clinic evaluation at baseline, which is repeated annually for 4 years to identify cases suspected of developing dementia and to measure longitudinal change on established clinical assessments. Subjects completed a set of self-administered experimental instruments at home or in the clinic designed to assess cognitive function and behavior, global change, activities of daily living, quality of life, and resource use. An additional "mail-in cognitive function questionnaire" was obtained separately by mail, 1 month before the other assessments. To evaluate the feasibility, efficiency, and validity of the home-based instruments in comparison with acquiring the same information during a clinic visit, subjects were randomized to 1 of 2 conditions in which the baseline and annual follow-up assessments are completed either at home ("home group") or at the study site during their clinic visits ("clinic group"). This initial report describes the ongoing 4-year longitudinal study and provides baseline results, which confirm the feasibility of obtaining home-based clinical information via mail or telephone. Initial results for the experimental instruments and for the book club are reported in separate accompanying articles.