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Now showing 1 - 10 of 20
  • Publication
    Living with Dementia: Caregiver Perspectives
    (2002-06-19) Karlawish, Jason
    About four million Americans currently live with Alzheimer’s disease (AD) or related forms of dementia. Because the disease process impairs language, insight, and judgment, family members become “caregivers.” These caregivers, either in part or in full, often make decisions on patients’ behalf. This Issue Brief summarizes a series of studies that describe how caregivers make decisions for AD patients, and caregiver perspectives on the quality of life for relatives with AD.
  • Publication
    Preclinical Alzheimer Disease - The Challenges Ahead
    (2013-01-01) Sperling, Reisa A; Karlawish, Jason; Johnson, Keith A
    There is growing recognition that the pathophysiological process of Alzheimer disease (AD) begins many years prior to clinically obvious symptoms, and the concept of a presymptomatic or preclinical stage of AD is becoming more widely accepted. Advances in biomarker studies have enabled detection of AD pathology in vivo in clinically normal older individuals. The predictive value of these biomarkers at the individual patient level, however, remains to be elucidated. The ultimate goal of identifying individuals in the preclinical stages of AD is to facilitate early intervention to delay and perhaps even prevent emergence of the clinical syndrome. A number of challenges remain to be overcome before this concept can be validated and translated into clinical practice.
  • Publication
    Ethics of Genetic and Biomarker Test Disclosures in Neurodegenerative Disease Prevention Trials
    (2015-04-07) Kim, Scott Y. H; Karlawish, Jason; Berkman, Benjamin E
    OBJECTIVE: Prevention trials for neurodegenerative diseases use genetic or other risk marker tests to select participants but there is concern that this could involve coercive disclosure of unwanted information. This has led some trials to use blinded enrollment (participants are tested but not told of their risk marker status). We examined the ethics of blinded vs transparent enrollment using well-established criteria for assessing the ethics of clinical research. METHODS: Normative analysis applying 4 key ethical criteria-favorable risk-benefit ratio, informed consent, fair subject selection, and scientific validity-to blinded vs transparent enrollment, using current evidence and state of Alzheimer disease (AD) and other prevention trials. RESULTS: Current evidence on the psychosocial impact of risk marker disclosure and considerations of scientific benefit do not support an obligation to use blinded enrollment in prevention trials. Nor does transparent enrollment coerce or involve undue influence of potential participants. Transparent enrollment does not unfairly exploit vulnerable participants or limit generalizability of scientific findings of prevention trials. However, if the preferences of a community of potential participants would affect the rigor or feasibility of a prevention trial using transparent enrollment, then investigators are required by considerations of scientific validity to use blinded enrollment. CONCLUSIONS: Considerations of risks and benefits, informed consent, and fair subject selection do not require the use of blinded enrollment for AD prevention trials. Blinded enrollment in AD prevention trials may sometimes be necessary because of the need for scientific validity, not because it prevents coercion or undue influence.
  • Publication
    Voting by Older Adults with Cognitive Impairments
    (2008-02-01) Karlawish, Jason
    This presidential election year reminds us of the importance of each vote and of the integrity of the electoral process. Recent elections have been decided by very narrow margins. In this context, the voting rights and capacity of persons with dementia warrant attention. About 4.5 million Americans currently live with dementia. Whether these citizens should vote raises a host of ethical, legal, and practical issues. At what point does someone lose the capacity to vote, and who decides? What kinds of assistance should these voters get, and who should provide it? And how can the voting rights of residents in long-term care facilities be protected?
  • Publication
    Desktop Medicine
    (2010-11-10) Karlawish, Jason
  • Publication
    Open Label Extension Studies and the Ethical Design of Clinical Trials
    (2001-08-01) Cassarett, David; Karlawish, Jason; Sankar, Pamela; Hirschman, Karen; Asch, David A.
  • Publication
    NIA-AA Research Framework: Toward a Biological Definition of Alzheimer's Disease
    (2018-04-10) Jack, Clifford R; Bennett, David A; Blennow, Kaj; Carrillo, Maria C; Dunn, Billy; Haeberlein, Samantha Budd; Holtzman, David M; Jagust, William; Jessen, Frank; Karlawish, Jason; Liu, Enchi; Molineuvo, Jose Luis; Montine, Thomas; Phelps, Creighton; Rankin, Katherine P; Rowe, Christopher C; Scheltens, Philip; Seimers, Eric; Snyder, Heather M; Sperling, Reisa
    In 2011, the National Institute on Aging and Alzheimer's Association created separate diagnostic recommendations for the preclinical, mild cognitive impairment, and dementia stages of Alzheimer's disease. Scientific progress in the interim led to an initiative by the National Institute on Aging and Alzheimer's Association to update and unify the 2011 guidelines. This unifying update is labeled a “research framework” because its intended use is for observational and interventional research, not routine clinical care. In the National Institute on Aging and Alzheimer's Association Research Framework, Alzheimer's disease (AD) is defined by its underlying pathologic processes that can be documented by postmortem examination or in vivo by biomarkers. The diagnosis is not based on the clinical consequences of the disease (i.e., symptoms/signs) in this research framework, which shifts the definition of AD in living people from a syndromal to a biological construct. The research framework focuses on the diagnosis of AD with biomarkers in living persons. Biomarkers are grouped into those of β amyloid deposition, pathologic tau, and neurodegeneration [AT(N)]. This ATN classification system groups different biomarkers (imaging and biofluids) by the pathologic process each measures. The AT(N) system is flexible in that new biomarkers can be added to the three existing AT(N) groups, and new biomarker groups beyond AT(N) can be added when they become available. We focus on AD as a continuum, and cognitive staging may be accomplished using continuous measures. However, we also outline two different categorical cognitive schemes for staging the severity of cognitive impairment: a scheme using three traditional syndromal categories and a six-stage numeric scheme. It is important to stress that this framework seeks to create a common language with which investigators can generate and test hypotheses about the interactions among different pathologic processes (denoted by biomarkers) and cognitive symptoms. We appreciate the concern that this biomarker-based research framework has the potential to be misused. Therefore, we emphasize, first, it is premature and inappropriate to use this research framework in general medical practice. Second, this research framework should not be used to restrict alternative approaches to hypothesis testing that do not use biomarkers. There will be situations where biomarkers are not available or requiring them would be counterproductive to the specific research goals (discussed in more detail later in the document). Thus, biomarker-based research should not be considered a template for all research into age-related cognitive impairment and dementia; rather, it should be applied when it is fit for the purpose of the specific research goals of a study. Importantly, this framework should be examined in diverse populations. Although it is possible that β-amyloid plaques and neurofibrillary tau deposits are not causal in AD pathogenesis, it is these abnormal protein deposits that define AD as a unique neurodegenerative diseaseamong different disorders that can lead to dementia. We envision that defining AD as a biological construct will enable a more accurate characterization and understanding of the sequence of events that lead to cognitive impairment that is associated with AD, as well as the multifactorial etiology of dementia. This approach also will enable a more precise approach to interventional trials where specific pathways can be targeted in the disease process and in the appropriate people.
  • Publication
    Older Adults’ Attitudes Toward Enrollment of Noncompetent Subjects Participating in Alzheimer’s Research
    (2009-02-01) Karlawish, Jason; Rubright, Jonathan; Casarett, David; Cary, Mark; Ten Have, Thomas; Sankar, Pamela
    OBJECTIVE: Research that seeks to enroll noncompetent patients with Alzheimer’s disease without presenting any potential benefit to participants is the source of substantial ethical controversy. The authors used hypothetical Alzheimer’s disease studies that included either a blood draw or a blood draw and lumbar puncture to explore older persons’ attitudes on this question. METHOD: Face-to-face interviews were conducted with 538 persons age 65 and older. Questions explored participants’ understanding of research concepts, their views on enrolling persons with Alzheimer’s disease in research, and their preferences regarding having a proxy decision maker, granting advance consent, and granting their proxy leeway to override the participant’s decision. Additional questions assessed altruism, trust, value for research, and perceptions of Alzheimer’s disease. RESULTS: The majority (83%) were willing to grant advance consent to a blood draw study, and nearly half (48%) to a blood draw plus lumbar puncture study. Most (96%) were willing to identify a proxy for research decision making, and most were willing to grant their proxy leeway over their advance consent: 81% for the blood draw study and 70% for the blood draw plus lumbar puncture study. Combining the preferences for advance consent and leeway, the proportion who would permit being enrolled in the blood draw and lumbar puncture studies, respectively, were 92% and 75%. Multivariate models showed that willingness to be enrolled in research was most strongly associated with a favorable attitude toward biomedical research. CONCLUSIONS: Older adults generally support enrolling noncompetent persons with Alzheimer’s disease into research that does not present a benefit to subjects. Willingness to grant their proxy leeway over advance consent and a favorable attitude about biomedical research substantially explain this willingness.
  • Publication
    Unfinished Business in Preventing Alzheimer Disease
    (2016-12-01) Karlawish, Jason; Langa, Kenneth M
  • Publication
    Measuring Decision-Making Capacity in Cognitively Impaired Individuals
    (2008-12-01) Karlawish, Jason
    Cognitive and functional losses are only part of the spectrum of disability experienced by persons with Alzheimer's disease and related dementias. They also experience losses in the ability to make decisions, known as decision-making capacity. Researchers have made substantial progress in developing a model of capacity assessment that rests upon the concept of the 4 decision-making abilities: understanding, appreciation, choice and reasoning. Empirical research has increased our understanding of the effects of late-life cognitive impairment on a person's ability to make decisions. This review examines studies of the capacity to consent to treatment, research and the management of everyday functional abilities. The results illustrate the clinical phenotype of the patient who retains the capacity to consent. They also suggest that measures of capacity can improve how researchers measure the benefits of cognitive enhancements and stage dementia.