ISSN:1090-6576    

DOI:10.1089/gte.1999.3.1

年代:1999

数据来源: MAL

摘要:

Several genes associated with Alzheimer disease (AD) have been localized and cloned; two genetic tests are already commercially available, and new tests are being developed. Genetic testing for AD—either for disease prediction or for diagnosis—raises critical ethical concerns. The multidisciplinary Alzheimer Disease Working Group of the Stanford Program in Genomics, Ethics, and Society (PGES) presents comprehensive recommendations on genetic testing for AD. The Group concludes that under current conditions, genetic testing for AD prediction or diagnosis is only rarely appropriate. Criteria for judging the readiness of a test for introduction into routine clinical practice typically rely heavily on evaluation of technical efficacy. PGES recommends a broader and more comprehensive approach, considering: 1) the unique social and historical meanings of AD; 2) the availability of procedures to promote good surrogate decision making for incompetent patients and to safeguard confidentiality; 3) access to sophisticated genetic counselors able to communicate complex risk information and effectively convey the social costs and psychological burdens of testing, such as unintentional disclosure of predictive genetic information to family members; 4) protection from inappropriate advertising and marketing of genetic tests; and 5) recognition of the need for public education about the meaning and usefulness of predictive and diagnostic tests for AD. In this special issue ofGenetic Testing, the PGES recommendations are published along with comprehensive background papers authored by Working Group memb

ISSN:1090-6576    

DOI:10.1089/gte.1999.3.3

年代:1999

数据来源: MAL

摘要:

Though Alzheimer disease (AD) has been recognized as a distinct entity since 1907, scientific understanding of, and public interest in, the disease remained very limited until the 1970s. The perception of AD as a significant problem has been substantially affected by cultural and demographic changes and by interest group and federal government initiatives. The recognition of AD has transformed senility from an expected stage of life into a "disease." It has also increased fear both of the individual effects of having AD and of the social consequences of AD in the population. Both the biotechnology industry and AD activist organizations will play a role in the social implications of genetic testing for AD.

ISSN:1090-6576    

DOI:10.1089/gte.1999.3.13

年代:1999

数据来源: MAL

摘要:

To assess the potential benefits and risks of genetic testing for Alzheimer disease (AD), patients and families, health care providers, and policymakers must understand the medical and epidemiologic aspects of the disease. This paper provides a brief overview of the symptoms, progression, and etiology of AD, as well as of the prevalence and incidence of the disease. The established and the controversial risk factors thought to be associated with the development of AD are described. Current methods for diagnosing and treating AD are also reviewed.

ISSN:1090-6576    

DOI:10.1089/gte.1999.3.21

年代:1999

数据来源: MAL

摘要:

Alzheimer disease (AD) has a drastic effect on the lives of those affected by the disease. Surprisingly little research has studied the personal and social consequences for AD patients. Many appear to go through six stages of change as the disease progresses, but any individual's path through the disease may vary substantially. AD also has a drastic effect on family members who serve as caregivers for people with the disease. These effects are much more studied and better documented. The burdens and, in some cases, benefits of the caregiver role differ from person to person. Race and ethnicity are among the variables that seem to play a role in the caregiver's response. The economic costs of AD are considerable, both for "formal" services, paid for in the money economy, and "informal" services, provided without monetary payment. The direct costs, both formal and informal, are largely, but not entirely, borne by the patient and the patient's family. The overall costs to so-ciety clearly amount to scores of billions of dollars.

ISSN:1090-6576    

DOI:10.1089/gte.1999.3.29

年代:1999

数据来源: MAL

摘要:

Two general classes of genes are associated with the development of Alzheimer disease (AD). The first group consists of genes that appear to cause AD when mutated, and the second category is composed of genes that are statistically associated with AD, depending on the inheritance of specific alleles. This paper reviews the current state of knowledge about the genetics of AD, and we then discuss the two molecular tests that are currently commercially available. These include a genetic test for mutations in the presenilin 1 (PS1) gene that can diagnose or predict a subset of early onset familial AD with a high degree of certainty. The value of the genetic test for the apolipoprotein (APOE) allele status is far less clear. Inheritance of the ε4 allele is associated with an increased risk of AD at a population level, but APOE genotyping is inappropriate for prediction of future disease in an individual and offers only a marginal increase in diagnostic certainty when symptomatic individuals are tested. In the future, genetic tests may become more broadly applicable to the diagnosis and prediction of AD. However, the utility of such tests is currently limited to a small subset of individuals because in the vast majority of AD cases no clear genetic or environmental cause has been defined

ISSN:1090-6576    

DOI:10.1089/gte.1999.3.37

年代:1999

数据来源: MAL

摘要:

Many studies have now confirmed the association between inheritance of the ε4 allele of the apolipoprotein E (APOE) gene and Alzheimer disease (AD). However, although the medical community holds the near-unanimous opinion that APOE genotyping should not be used for prediction in asymptomatic individuals, controversy remains about whether it should be used for diagnosis in patients who show signs of dementia. We assessed critically the recent clinical studies, on the basis of four criteria recommended to ensure safety and effectiveness of genetic tests. We also developed a formal framework for evaluating the usefulness of APOE genotyping using decision-theoretic principles. We conclude that neither the presence nor absence of an ε4 allele provides diagnostic certainty, and the proper interpretation of either result in heterogeneous populations requires further investigation. The appropriate role of APOE genotyping among elements of a traditional assessment for AD has not been determined. Whether APOE genotyping provides sufficient information to change patient management decisions has not been determined. APOE genotyping presents foreseeable, significant psychosocial consequences for family members that must be weighed against any psychosocial benefits. Therefore, the diagnostic use of APOE genotyping outside research settings is premature until such testing is shown to be of practical valu

ISSN:1090-6576    

DOI:10.1089/gte.1999.3.47

年代:1999

数据来源: MAL

摘要:

The utility of genetic testing in preventing the onset of conditions such as Alzheimer disease (AD) depends upon categorizing individuals based on their "risk" of illness. Although no strategies to prevent the occurrence of AD have been proven effective, the promise of the new molecular medicine is based on the assumption that those "at risk" can be identified, counseled about their likelihood of developing a disease, and prescribed specific preventive interventions. We suggest that this paradigm of disease prevention through risk stratification has limitations that have not been fully explored. Within the fields of cognitive and health psychology, research has addressed how individuals understand the numeric presentation of uncertain future events; this research often focuses on the "perceptual pathology" of lay people. The uncertainty inherent in the risk estimates themselves is rarely considered, nor has research addressed how those risk estimates are created. There has been limited work to date focused on genetic risk assessment, and little is known about how individuals might understand the meaning or consequences of being at genetic risk for AD. An emerging social science critique of concepts of risk in genetic medicine offers a broader perspective, examining the process of producing scientific risk estimates as well as the response of individual patients, such as the experience of embodied risk that is central to genetic testing. Making fully informed choices about genetic testing for AD may prove more difficult than our current model of ethical practice suggests.

ISSN:1090-6576    

DOI:10.1089/gte.1999.3.55

年代:1999

数据来源: MAL

摘要:

The availability of genetic tests to diagnose or predict Alzheimer disease (AD) causes a shift in the way people think about the condition and how they assess the options available to them. Decision analysis is a quantitative approach for dealing with the uncertainties inherent in many medical decisions, including decisions about genetic testing. Decision analysis does not guarantee a good outcome, but aims to yield better overall average results by providing a framework for people to evaluate their options and minimize cognitive biases. We provide an overview of the decision analysis process, including the terms and tools commonly associated with it. We also use a recent example to demonstrate one way decision analysis has been applied to genetics in the medical literature. This paper is an introduction to subsequent papers that explore the specific question of whether decision analysis is a helpful tool for understanding the uncertainty inherent in probabilistic information about genetic risk for AD.

ISSN:1090-6576    

DOI:10.1089/gte.1999.3.65

年代:1999

数据来源: MAL

摘要:

Decision analysis may be useful to people facing Alzheimer disease (AD) decisions. The use of decision analysis in three such cases is reported. The first case involved a middle-aged person worried about early-onset AD and deciding whether to seek genetic testing. The analysis let the participant reject testing and consider innovative care options. The second case involved a middle-aged person concerned about later-onset AD. The analysis for her was more complex, and led to the assignment of some limited value on genetic testing for her. The third case revolved around a caregiver's treatment decisions for a patient with severe AD. It led her to recognize the importance of factors she had not previously considered. In each of the three cases, the intensive process of decision analysis appears to have improved the subject's decision.

ISSN:1090-6576    

DOI:10.1089/gte.1999.3.71

年代:1999

数据来源: MAL