Kimberly A. Quaid

Disclosure of APOE Genotype for Risk of Alzheimer's Disease

BACKGROUND The apolipoprotein E (APOE) genotype provides information on the risk of Alzheimers disease, but the genotyping of patients and their family members has been discouraged. We examined the effect of genotype disclosure in a prospective, randomized, controlled trial. METHODS We randomly assigned 162 asymptomatic adults who had a parent with Alzheimers disease to receive the results of their own APOE genotyping (disclosure group) or not to receive such results (nondisclosure group). We measured symptoms of anxiety, depression, and test-related distress 6 weeks, 6 months, and 1 year after disclosure or nondisclosure. RESULTS There were no significant differences between the two groups in changes in time-averaged measures of anxiety (4.5 in the disclosure group and 4.4 in the nondisclosure group, P=0.84), depression (8.8 and 8.7, respectively; P=0.98), or test-related distress (6.9 and 7.5, respectively; P=0.61). Secondary comparisons between the nondisclosure group and a disclosure subgroup of subjects carrying the APOE epsilon4 allele (which is associated with increased risk) also revealed no significant differences. However, the epsilon4-negative subgroup had a significantly lower level of test-related distress than did the epsilon4-positive subgroup (P=0.01). Subjects with clinically meaningful changes in psychological outcomes were distributed evenly among the nondisclosure group and the epsilon4-positive and epsilon4-negative subgroups. Baseline scores for anxiety and depression were strongly associated with post-disclosure scores of these measures (P<0.001 for both comparisons). CONCLUSIONS The disclosure of APOE genotyping results to adult children of patients with Alzheimers disease did not result in significant short-term psychological risks. Test-related distress was reduced among those who learned that they were APOE epsilon4-negative. Persons with high levels of emotional distress before undergoing genetic testing were more likely to have emotional difficulties after disclosure. (ClinicalTrials.gov number, NCT00571025.)

Who seeks genetic susceptibility testing for Alzheimer’s disease? Findings from a multisite, randomized clinical trial

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.

reasons for Seeking Genetic Susceptibility Testing Among First-degree Relatives of People With Alzheimer Disease

&NA; 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.

Genetic susceptibility testing versus family history- based risk assessment: Impact on perceived risk of Alzheimer disease

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 ε4-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.

Prenatal screening and pregnant women's attitudes toward the abortion of defective fetuses.

We studied the attitudes of 490 pregnant women toward the abortion of defective fetuses. Three hundred of these women were participating in a prenatal screening program for neural tube defects. Although theoretical accounts of the effects of behavior on attitude would suggest that participation in a screening program would affect abortion attitudes, evidence in support of such an association was weak. The overwhelming majority of women, regardless of whether they had participated in the screening program, believed that women are justified in having an abortion in the face of fetal abnormality. There was a sharp increase in the number of screening program participants who said they would have an abortion when the probability of the fetus being affected with a neural tube defect rose from 95 per cent to 100 per cent.

The neurogenetics genie: testing for the Huntington's disease mutation.

Even though the discovery of the HD gene will make genetic testing much easier to perform, until there is an effective treatment, it will be no easier for HD families to learn who among them carries the mutation. We believe that the standard of care for obtaining genetic testing for HD, as well as for other inherited neurodegenerative disorders, must continue to include extensive counseling, psychological assessment and support, a neurologic examination, and post-test follow-up. We advocate a flexible approach consistent with the individuals particular needs, but we emphasize that it is essential that these basic elements be adequately addressed.

Living at Risk: Concealing Risk and Preserving Hope in Huntington Disease

Much of the qualitative research on Huntington disease has focused on the genetic testing aspects of HD. The overall purpose of this qualitative study was to gather information about the everyday experience of living with the risk of developing Huntington disease in a sample of individuals at risk for HD who have chosen not to pursue genetic testing. Data for this article was obtained from unstructured, open-ended qualitative interviews of a sample of people participating in the PHAROS study. PHAROS, the Prospective Huntington At-Risk Observational Study, is a multi-site study that aims to establish whether experienced clinicians can reliably determine the earliest clinical symptoms of Huntington disease in individuals at 50% risk for HD who have chosen not to undergo genetic testing. Interviews were conducted at six PHAROS research sites across the United States. In this paper, the research team used qualitative description to construct and explore two main themes: (1) careful concealment of risk as an act of self-preservation and (2) preserving hope.

Informed consent for a prescription drug: Impact of disclosed information on patient understanding and medical outcomes

Abstract Based on the two legal standards of informed consent currently in use, the Medical Practice Standard and the Reasonable Person Standard, two disclosures containing information about the risks and benefits of the anticonvulsant, Carbamazepine, were empirically derived. One of these two disclosures was randomly given to a sample of 39 seizure patients and the parents of pediatric seizure patients prescribed this drug. Subjects were interviewed either immediately after disclosure and at followup, or at followup only. The results provide no evidence for the hypothesized negative effects — anxiety, treatment refusal, reduced compliance and increased side effects — of providing patients with extensive disclosures about prescription drugs.

Presymptomatic testing for huntington diseases: Recommendations for counseling.

The discovery of a genetic marker linked to the Huntington disease (HD) gene made it possible to perform presymptomatic genetic testing for this late onset disorder. The first two pilot research programs in the United States, at Massachusetts General Hospital and Johns Hopkins Hospital, began offering testing in the Fall of 1986. Twenty-three centers are now offering this testing as part of their clinical service. As testing for this and other late onset diseases becomes more widespread, it is important to assess what we have learned about offering this test to those at risk. This article presents recommendations based on the authors 5 years of experience offering presymptomatic testing for HD in order to alert counselors to the complexities of offering this type of service.

Fear of health insurance loss among individuals at risk for huntington disease

Genetic testing in Huntington disease, an inherited ultimately fatal neurodegenerative disorder, is infrequent despite wide availability. Factors influencing the decision to pursue testing are largely unknown. We conducted a prospective longitudinal observational study of 1,001 individuals in North America who were at risk for Huntington disease who had not pursued genetic testing prior to enrollment. We evaluated the rationale for remaining untested at baseline, determined the concerns of those who eventually pursued testing, and assessed the populations psychological attributes. We contrasted responses between those who did and did not pursue testing, and between United States and Canadian residents. The principal reasons for remaining untested were comfort with risk and uncertainty and the inability to “undo” knowledge gained. After enrollment, 83 individuals [8.3%] pursued genetic testing. Their greatest concern was losing health insurance, and 41.6% of them [vs. 6.7% of those who did not pursue testing; P < 0.001] reported paying out of pocket for testing or other medical services to conceal their genetic risk from their insurer/employer. Among individuals who were tested, more United States residents [46.1%] than Canadian residents [0.0%; P = 0.02] paid out of pocket for health services or genetic testing. Psychological attributes were similar among individuals who did and did not pursue testing. Individuals at risk for Huntington disease who pursued genetic testing feared losing medical insurance, and many paid out of pocket for medical services. Alleviating the fear of health insurance loss may help those who want to pursue genetic testing for many other conditions. [ClinicalTrials.gov number, NCT0052143].