Alzheimer Disease: Marson D

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.

Karlawish J, Kim SY, Knopman D, van Dyck CH, James BD, Marson D. · Department of Medicine, Alzheimer's Disease Center, Leonard Davis Institute for Health Economics, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, School of Medicine, PA, USA. · Am J Geriatr Psychiatry. · Pubmed #18556397 No free full text.

Abstract: OBJECTIVE: Among Alzheimer disease (AD) patients enrolled in a clinical trial, the authors assessed the ability of a standardized capacity assessment procedure to identify persons who are capable of giving their own informed consent. DESIGN: Cross-sectional interview. SETTING: Thirteen sites participating in a randomized and placebo controlled study of simvastatin for the treatment of mild to moderate AD. PARTICIPANTS: Persons with mild to moderate AD and their study partners enrolled in the simvastatin clinical trial. MEASUREMENTS: Interviews to assess decision-making capacity using the MacArthur Competency Assessment Tool for Clinical Research (MacCAT-CR). RESULTS: Judges blinded to the subject's clinical status had a high rate of agreement on patients capable of giving their own informed consent (kappa = 0.73). The understanding subscale had the best receiver operator characteristic and an analysis of positive and negative predictive values over a range of hypothetical prevalences of incapacity to consent demonstrated the value of a range of understanding cut-points. CONCLUSION: Among mild to moderate AD patients, enrolled in an actual clinical trial, these results suggest evidence based guidelines for using the MacCAT-CR understanding subscale to help guide judgments about whether a patient has the capacity to consent.

Karlawish J, Kim SY, Knopman D, van Dyck CH, James BD, Marson D. · Department of Medicine, Alzheimer's Disease Center, Leonard Davis Institute for Health Economics, University of Pennsylvania, School of Medicine, Philadelphia, PA 19104, USA. · Am J Geriatr Psychiatry. · Pubmed #18310554 No free full text.

Abstract: OBJECTIVE: To examine the views of Alzheimer disease (AD) patients and their study partners on the ethics of proxy consent for clinical research. DESIGN: Cross-sectional interview. SETTING: At the 13 study sites of a randomized and placebo controlled study of simvastatin for the treatment of AD. PARTICIPANTS: Patients with mild-to-moderate AD and their study partners enrolled in an Alzheimer's Disease Cooperative Study trial of simvastatin. MEASUREMENTS: Interviews to assess how participants made the decision to enroll in a randomized controlled trial and their attitudes on proxy consent. RESULTS: Study partners of patients judged not capable of providing informed consent reported the same degree of patient involvement in the decision to enroll as the study partners of patients capable of providing informed consent. Most study partners and patients supported proxy consent for this clinical trial and nearly all patients chose their study partner as their proxy. Study partners generally made research enrollment decisions based on what they thought would maximize the patient's well-being as opposed to a substituted judgment. CONCLUSIONS: Patients and their study partners who were enrolled in a clinical trial supported proxy consent both for themselves and as a matter of policy. Our findings suggest that policies that require substituted judgments may not accord with the views of the people currently participating in AD clinical trials.

Martin R, Griffith HR, Belue K, Harrell L, Zamrini E, Anderson B, Bartolucci A, Marson D. · Department of Neurology and Alzheimer's Disease Research Center, University of Alabama at Birmingham, and VA Medical Center, Birmingham, AL 35294-0017, USA. · Am J Geriatr Psychiatry. · Pubmed #18263665 No free full text.

Abstract: OBJECTIVE: The objective of this study was to investigate change over time in financial abilities in patients with mild Alzheimer disease (AD). METHODS: The authors conducted a prospective 1-year longitudinal study at a large southern U.S. metropolitan-area medical school university. Participants included healthy older adults (N=63) and patients with mild AD (N=55). The authors conducted a standardized performance measure of financial capacity. Performance was assessed on 18 financial tasks, nine domains of financial activity, and overall financial capacity. Capacity outcomes classifications (capable, marginally capable, or incapable) for domains and overall performance were made using cut scores referenced to comparison group performance. RESULTS: At baseline, patients with mild AD performed significantly below healthy older adults on 16 of 18 tasks, on all nine domains, and on overall financial capacity. At one-year follow up, comparison group performance was stable on all variables. In contrast, patients with mild AD showed substantial declines in overall financial capacity, on eight of nine domains, and on 12 of 18 tasks. Similarly, the proportion of the mild AD group classified as marginally capable and incapable increased substantially over one year for the two overall scores and for five financial domains. CONCLUSIONS: Financial capacity is already substantially impaired in patients with mild AD at baseline and undergoes rapid additional decline over one year. Relative to the comparison group, overall financial capacity performance in the AD group declined 10%, from approximately 80% of the comparison group performance at baseline to 70% at follow up. Financial skills showed differential rates of decline on both simple and complex tasks. Of clinical and public policy interest was the declining judgment of patients with mild AD regarding simple fraud schemes. The study supports the importance of prompt financial supervision and planning for patients newly diagnosed with AD.

Galasko D, Bennett DA, Sano M, Marson D, Kaye J, Edland SD, Anonymous00339. · Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093-0624, USA. · Alzheimer Dis Assoc Disord. · Pubmed #17135809 No free full text.

Abstract: BACKGROUND: In primary prevention trials for Alzheimer disease, the inception cohort typically has normal or minimally impaired complex activities of daily living (ADL). ADL change during a trial could trigger detailed evaluation or serve as an outcome measure. A brief, easily administered, and reliable ADL rating scale would assist prevention studies. OBJECTIVES: To develop an ADL scale for prevention trials that allows self-rating or completion by informants. METHODS: The Activities of Daily Living-Prevention Instrument (ADL-PI) was developed, comprising 15 ADL and 5 physical function questions. Six hundred forty-four elderly subjects participating in the Prevention Instrument Project completed a self-rated version of the ADL-PI, and informants for 632 subjects completed an informant version. Informants also completed a Mild Cognitive Impairment (MCI) ADL questionnaire to allow comparisons. RESULTS: Subjects performed well on all ADL scales at baseline. Completion of the ADL-PI questionnaires at home or in-clinic yielded comparable information. Scores from baseline to 3 months had good reliability. The ADL-PI, obtained from either self-report or informants, discriminated between subjects rated as CDR 0 and CDR 0.5. Subjects with worse baseline cognitive performance also had slightly worse ADL-PI scores. Preliminary analysis indicates that subjects who triggered cognitive evaluations had slightly lower baseline ADL-PI scores by both self and informant reports. CONCLUSIONS: The ADL-PI can be completed at home or in clinic, and has adequate reliability. The utility of self-administered and informant versions and predictive value of reported deficits requires further follow-up.

Karlawish JH, Knopman D, Clark CM, Morris JC, Marson D, Whitehouse PJ, Kawas CH. · Internal Ethics Committee of the Alzheimer's Disease Cooperative Study. · IRB. · Pubmed #12737167 No free full text.

This publication has no abstract.

Harrell LE, Marson D, Chatterjee A, Parrish JA. · Alzheimer's Disease Center and Department of Neurology, VA Medical Center, Birmingham, Alabama, USA. · Alzheimer Dis Assoc Disord. · Pubmed #10994658 No free full text.

Abstract: The bedside and office assessment of cognitive abilities in moderately to severely impaired patients with Alzheimer disease could be enhanced by a well-standardized instrument. The authors' group has developed such an instrument (i.e., Severe Mini-Mental State Examination; SMMSE) to assess this population. Based on the Folstein Mini-Mental State Examination (MMSE), the SMMSE, which totals 30 points, was designed to briefly assess cognitive domains relatively preserved in moderate to severe Alzheimer disease. One hundred eighty-two patients with possible or probable Alzheimer disease were administered both the MMSE and SMMSE. Performances on the SMMSE and MMSE were found to correlate significantly only when MMSE fell below 9 points (p < 0.0001). However, as performance on the MMSE approached floor levels, patients continued to score at half maximal levels on the SMMSE. Functional staging with the Clinical Dementia Rating Scale and the Global Deterioration Scale also were found to significantly correlate with performance on the SMMSE (p < 0.001). Test-retest performance on both the SMMSE and MMSE was relatively stable over a period of 5 months. Inter-rater reliability of the SMMSE was excellent. These results suggest that the SMMSE has both construct and criterion validity for assessing severely impaired Alzheimer disease patients. Our results also suggest that the SMMSE may be a useful instrument for assessing severely impaired patients at the bedside and in the office.

Marson D, Harrell L. · Department of Neurology, Alzheimer's Disease Center, and Center for Aging, University of Alabama at Birmingham, Birmingham, AL 35294, USA. · Semin Clin Neuropsychiatry. · Pubmed #10229792 No free full text.

Abstract: Loss of medical decision making capacity (competency) is an inevitable consequence of Alzheimer's disease (AD) and is an important subject for neuropsychological investigation. Consent capacity involves a complex set of comprehension, encoding, information processing, decision making, and communication abilities, which ultimately must have an explicit neurological basis. This article examines the role of executive dysfunction in loss of consent capacity in patients with AD. The authors first describe a cognitive neuropsychological model for understanding loss of consent capacity in AD. The article also reviews neuropsychological studies that have used a psychometric instrument to test consent capacity under different legal standards (Capacity to Consent to Treatment Instrument). These studies indicate that when multiple cognitive functions are associated with declining competency of AD patients on the Capacity to Consent to Treatment Instrument legal standards, measures of simple executive function are the predominant predictors. These empirical findings are discussed and related to the conceptual model. The findings support the growing body of literature linking frontal neural systems and executive cognitive functions to competency and to higher order functional capacities.