Susceptibility testing for common, complex adult-onset diseases is projected to become more commonplace as the rapid pace of genomic discoveries continues, and evidence regarding the potential benefits and harms of such testing is needed to inform medical practice and health policy. Apolipoprotein E (APOE) testing for risk of Alzheimer’s disease (AD) provides a paradigm in which to examine the process and impact of disclosing genetic susceptibility for a prevalent, severe and incurable neurological condition. This review summarizes findings from a series of multi-site randomized clinical trials examining psychological and behavioral responses to various methods of genetic risk assessment for AD using APOE disclosure. We discuss challenges involved in disease risk estimation and communication and the extent to which participants comprehend and perceive utility in their genetic risk information. Findings on the psychological impact of test results are presented (e.g., distress), along with data on participants’ health behavior and insurance purchasing responses (e.g., long term care). Finally, we report comparisons of the safety and efficacy of intensive genetic counseling approaches to briefer models that emphasize streamlined processes and educational materials. The implications of these findings for the emerging field of personal genomics are discussed, with directions identified for future research.
This study evaluates the extent to which psychological adaptation (validated measures of depressive symptoms, anxiety, and test-specific distress) after genetic susceptibility testing is influenced by changes in beliefs about Alzheimer's disease (AD) and sharing of test results with others. Adult children of AD patients (N=269) from a randomized clinical trial involving genetic testing for apolipoprotein E (APOE) provided information before, as well as 6 weeks and 12 months after results disclosure. The levels of adaptation varied highly among participants at 12-month assessment. Participants who learned that they were ε4 negative (lower risk) had a reduction in perceived risk and concern about developing AD compared with those who learned that they were ε4 positive. Those who received results through an extended educational protocol (three in-person visits) had a larger decline in AD concern than those in a condensed protocol (educational brochure and two in-person visits). Increase in AD concern 6 weeks after disclosure was associated with increase in depression scores (b=0.20, P<0.01) and anxiety levels (b=0.20, P<0.01), and higher distress associated with AD genetic testing (b=0.18, P=0.02) 1 year after testing. Increase in perceived risk (b=0.16, P=0.04) was also associated with higher AD genetic testing distress. Sharing the test results with health professionals and friends (but not family) was associated with decrease in depression (b= −0.11, P=0.05) and anxiety levels (b= −0.16, P<0.01), respectively after a year. Enhancing discussion with regard to risks and concerns about AD during pretesting counseling and obtaining support through sharing the results after testing may help facilitate test recipients' long-term psychological adaptation.
susceptibility genetic testing; AD; APOE; results disclosure; communication; risk perceptions
This study evaluates the extent to which psychological adaptation (validated measures of depressive symptoms, anxiety, and test-specific distress) after genetic susceptibility testing is influenced by changes in beliefs about Alzheimer's disease (AD) and sharing of test results with others. Adult children of AD patients (N=269) from a randomized clinical trial involving genetic testing for apolipoprotein E (APOE) provided information before, as well as 6 weeks and 12 months after results disclosure. The levels of adaptation varied highly among participants at 12-month assessment. Participants who learned that they were ɛ4 negative (lower risk) had a reduction in perceived risk and concern about developing AD compared with those who learned that they were ɛ4 positive. Those who received results through an extended educational protocol (three in-person visits) had a larger decline in AD concern than those in a condensed protocol (educational brochure and two in-person visits). Increase in AD concern 6 weeks after disclosure was associated with increase in depression scores (b=0.20, P<0.01) and anxiety levels (b=0.20, P<0.01), and higher distress associated with AD genetic testing (b=0.18, P=0.02) 1 year after testing. Increase in perceived risk (b=0.16, P=0.04) was also associated with higher AD genetic testing distress. Sharing the test results with health professionals and friends (but not family) was associated with decrease in depression (b = −0.11, P = 0.05) and anxiety levels (b=−0.16, P<0.01), respectively after a year. Enhancing discussion with regard to risks and concerns about AD during pretesting counseling and obtaining support through sharing the results after testing may help facilitate test recipients' long-term psychological adaptation.
susceptibility genetic testing; AD; APOE; results disclosure; communication; risk perceptions
Genetic risk for Alzheimer’s disease (AD) may be conferred by the susceptibility polymorphism apolipoprotein E (APOE), where the ε4 allele increases the risk of developing late-onset Alzheimer’s disease but is not a definitive predictor of the disease, or by autosomal dominant mutations (e.g., the presenilins), which almost inevitably result in early-onset familial Alzheimer’s disease. The purpose of this study was to compare the psychological impact of using these two different types of genetic information to disclose genetic risk for AD to family members of affected patients.
Data were compared from two separate protocols. The Risk Evaluation and Education for Alzheimer’s Disease (REVEAL) Study is a randomized, multi-site clinical trial that evaluated the impact of susceptibility testing for Alzheimer’s disease with APOE in 101 adult children of Alzheimer’s disease patients. A separate study, conducted at the University of Washington, assessed the impact of deterministic genetic testing by disclosing presenilin-1, presenilin-2, or TAU genotype to 22 individuals at risk for familial Alzheimer’s disease or frontotemporal dementia. In both protocols, participants received genetic counseling and completed the Impact of Event Scale (IES), a measure of test-specific distress. Scores were analyzed at the time point closest to one year post-disclosure at which IES data were available. The role of genetic test result (positive vs. negative) and type of genetic testing (deterministic vs. susceptibility) in predicting log-transformed IES scores was assessed with linear regression, controlling for age, gender, and time from disclosure.
Subjects from the REVEAL Study who learned that they were positive for the susceptibility gene APOE ε4+ experienced similar, low levels of test-specific distress compared to those who received positive results of deterministic testing in the University of Washington study (p= 0.78). APOE ε4+ individuals in the susceptibility protocol experienced more test-specific distress than those who tested ε4− in the same study (p= 0.04); however, among those receiving deterministic test disclosure, the subjects who received positive results did not experience significantly higher levels of distress when compared to those who received negative results (p= 0.88).
The findings of this preliminary study, with limited sample size, suggest that the test-related distress experienced by those receiving positive results for a deterministic mutation is similar to the distress experienced by those receiving positive results from genetic susceptibility testing, and that the majority of participants receiving genotype disclosure do not experience clinically significant distress as indicated by IES scores one year after learning of their test results.
genetic susceptibility testing; deterministic testing; Alzheimer’s disease; APOE; genetic counseling
Risk information for Alzheimer disease (AD) may be communicated through susceptibility gene disclosure, even though this is not currently in clinical use. The REVEAL Study is the first randomized clinical trial of risk assessment for AD with apolipoprotein E (APOE) genotype and numerical risk estimate disclosure. We examined whether APOE genotype and numerical risk disclosure to asymptomatic individuals at high risk for AD alters health behaviors. One hundred sixty-two participants were randomized to either intervention (APOE disclosure) or control (no genotype disclosure) groups. Subjects in both groups received numerical lifetime risk estimates of future AD development based on sex and family history of AD. The intervention group received their APOE genotype. Subjects were informed that no proven preventive measures for AD existed and given an information sheet on preventative therapies under investigation. Participants who learned they were ε4 positive were significantly more likely than ε4 negative participants to report AD-specific health behavior change 1 year after disclosure (adjusted odds ratio: 2.73; 95% confidence interval: 1.14, 6.54; P = 0.02). Post hoc analyses revealed similar significant associations between numerical lifetime risk estimates and self-report of AD-specific health behavior change. Despite lack of preventive measures for AD, knowledge of APOE genotype, numerical lifetime risk, or both, influences health behavior.
Alzheimer; memory; health behavior change; risk assessment
Most studies of HIV disclosure in Africa have focused on disclosure to spouses and sexual partners, and particularly among women. Few have examined disclosure to family, friends, and others. Understanding the reasons for disclosure and nondisclosure and how these reasons differ by disclosure target is needed for effective prevention interventions. Using a case study design and content analysis, this study explored whether the reasons for disclosure decisions differ by the nature of the relationship to the disclosure target. Semistructured interviews were conducted with 40 HIV clients in Kampala, with even stratification by gender and age. Most (95%) respondents reported disclosing to someone; among these, 84% disclosed to family members, 63% to friends, 21% to workplace colleagues, and 18% to others. Of the 24 participants who had a spouse, 13 (54%) reported disclosing to a spouse. The most common reasons for disclosure were to receive support (76%), associated with disclosure to family members; relationship ties (76%), associated with disclosure to all target types; explaining change in behavior or appearance (61%), associated with disclosing to family and friends; and HIV prevention (50%), associated with disclosure to spouse/partner and friends. The most common reasons for nondisclosure were: fear of abandonment, particularly among young women disclosing to spouse/partner; inaccessibility to the disclosure target; and not wanting to worry/upset the disclosure target. This exploratory analysis suggests that reasons for disclosure and nondisclosure differ depending on the targets of disclosure, highlighting the need for tailoring interventions for improving disclosure decisions making and outcomes.
Perceptions about the pros and cons of genetic susceptibility testing are among the best predictors of test utilization. How actual testing changes such perceptions has yet to be examined.
In a clinical trial, first-degree relatives of patients with Alzheimer disease received genetic risk assessments for Alzheimer disease including APOE disclosure. Participants rated 11 possible benefits associated with genetic testing (pros) and 10 risks or limitations (cons) before genetic risk disclosure and again 12 months afterward.
Pros were rated higher than cons at baseline (3.53 vs. 1.83, P < 0.001) and at 12 months after risk disclosure (3.33 vs. 1.88, P < 0.001). Ratings of pros decreased during the 12-month period (3.33 vs. 3.53, P < 0.001). Ratings of cons did not change (1.88 vs. 1.83, P = 0.199) except for a three-item discrimination subscale which increased (2.07 vs. 1.92, P = 0.012). Among specific pros and cons, three items related to prevention and treatment changed the most.
The process of APOE genetic risk assessment for Alzheimer disease sensitizes some to its limitations and the risks of discrimination; however, 1-year after disclosure, test recipients still consider the pros to strongly outweigh the cons.
Alzheimer; pros; cons; benefits; discrimination; genetics; risk; APOE; susceptibility testing; education
Aim: Among mothers undergoing BRCA1/2 testing and their spouses/partners, this study sought to examine decision support needs and motivations for family communication of genetic risk information to asymptomatic children. Methods: This study gathered data from 213 tested mothers and 104 of their untested parenting partners 1 month after maternal receipt of genetic test results and upon making a decision about communicating genetic information to their child (ages 8–21 years). Data include parents' perceived needs for family communication decision support, decision motivations, and parent-child communication. Results: Parents reported high decision support needs (e.g., educational materials, professional counseling, peer assistance). Motivations for disclosure to children among mothers and partners focused on promoting the parent-child bond and maintaining family health (55.3% and 75%, respectively) and promoting positive child affect (44.7% and 25.5%, respectively). Motivations for nondisclosure to children among mothers and partners focused on the lack of appropriateness (69.6% and 51.3%, respectively) and relative importance of genetic test results (30.4% and 48.7%, respectively). Significant discrepancies in parental motivation for family communication were observed. Decision support needs were highest among disclosing mothers with affect-related motivations [t (129)=2.47; p=0.01]. Parent-child communication was poorest among nondisclosing mothers concerned about the appropriateness of genetic information for their child [t (77)=−3.29; p=.002]. Conclusions: Parents receiving information about hereditary cancer predisposition have unmet needs when making decisions about disclosing genetic risk information to their asymptomatic children. These data can guide the development of cancer risk communication decision support interventions for parents undergoing such testing.
The apolipoprotein E (APOE) genotype provides information on the risk of Alzheimer's 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.
We randomly assigned 162 asymptomatic adults who had a parent with Alzheimer's 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.
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 non-disclosure group and a disclosure subgroup of subjects carrying the APOE ε4 allele (which is associated with increased risk) also revealed no significant differences. However, the ε4-negative subgroup had a significantly lower level of test-related distress than did the ε4-positive subgroup (P=0.01). Subjects with clinically meaningful changes in psychological outcomes were distributed evenly among the nondisclosure group and the ε4-positive and ε4-negative subgroups. Baseline scores for anxiety and depression were strongly associated with post-disclosure scores of these measures (P<0.001 for both comparisons).
The disclosure of APOE genotyping results to adult children of patients with Alzheimer's disease did not result in significant short-term psychological risks. Test-related distress was reduced among those who learned that they were APOE ε4–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.)
This paper explores whether and how the behavioral impact of genotype disclosure can be disentangled from the impact of numerical risk estimates generated by genetic tests. Secondary data analyses are presented from a randomized controlled trial of 162 first-degree relatives of Alzheimer’s disease (AD) patients. Each participant received a lifetime risk estimate of AD. Control group estimates were based on age, gender, family history, and assumed ε4-negative apolipoprotein E (APOE) genotype; intervention group estimates were based upon the first three variables plus true APOE genotype, which was also disclosed. AD-specific self-reported behavior change (diet, exercise, and medication use) was assessed at 12 months. Behavior change was significantly more likely with increasing risk estimates, and also more likely, but not significantly so, in ε4-positive intervention group participants (53% changed behavior) than in control group participants (31%). Intervention group participants receiving ε4-negative genotype feedback (24% changed behavior) and control group participants had similar rates of behavior change and risk estimates, the latter allowing assessment of the independent effects of genotype disclosure. However, collinearity between risk estimates and ε4-positive genotypes, which engender high-risk estimates, prevented assessment of the independent effect of the disclosure of an ε4 genotype. Novel study designs are proposed to determine whether genotype disclosure has an impact upon behavior beyond that of numerical risk estimates.
Disclosure of HIV status after HIV voluntary counseling and testing (VCT) has important implications for the spread of the HIV epidemic and the health of individuals who are HIV positive. Here, we use individual and couples-level data for currently-married respondents from an ongoing longitudinal study in rural Malawi to (1) examine the extent of HIV status disclosure by HIV serostatus (2) identify reasons for not sharing one’s HIV status with a spouse, and (3) evaluate the reliability of self-reports of HIV status disclosure. We find that disclosure of HIV status is relatively common among rural Malawians, where most have shared their status with a spouse, and many disclose to others in the community. However, there are significant differences in disclosure patterns by HIV status and gender. Factors associated with non-disclosure are also gendered, where women who perceive greater HIV/AIDS stigma and are HIV positive are less likely to disclose HIV status to a spouse, and men who are worried about HIV infection from extramarital partners are less likely to disclose their HIV status to a spouse. Finally, we test the reliability of self-reported HIV status disclosure and find that self-reports of HIV positive men are of questionable reliability.
HIV; sub-Saharan Africa; Malawi; stigma; VCT
This study evaluates the Alzheimer disease risk perceptions of individuals who accurately recall their genetics-based Alzheimer disease risk assessment.
Two hundred forty-six unaffected first-degree relatives of patients with Alzheimer disease were enrolled in a multisite randomized controlled trial examining the effects of communicating APOE genotype and lifetime Alzheimer disease risk information.
Among the 158 participants who accurately recalled their Alzheimer disease risk assessment 6 weeks after risk disclosure, 75 (47.5%) believed their Alzheimer disease risk was more than 5% points different from the Alzheimer disease risk estimate they were given. Within this subgroup, 69.3% believed that their Alzheimer disease risk was higher than what they were told (discordant high), whereas 30.7% believed that their Alzheimer disease risk was lower (discordant low). Participants with a higher baseline risk perception were more likely to have a discordant-high risk perception (P < 0.05). Participants in the discordant-low group were more likely to be APOE ε4 positive (P < 0.05) and to score higher on an Alzheimer disease controllability scale (P < 0.05).
Our results indicate that even among individuals who accurately recall their Alzheimer disease risk assessment, many people do not take communicated risk estimates at face value. Further exploration of this clinically relevant response to risk information is warranted.
risk recall; risk perception; Alzheimer disease; genetic susceptibility testing
Family communication of genetic risk information is a complex process. Currently, there are no evidence-based interventions to help genetics professionals facilitate the process of disclosure within families. This study was designed to create a framework to assist in the development of tools to support patients in communicating genetic risk information to family members. A systematic review identified the factors relevant in communicating genetic risk information in families. A guiding theory for the proposed framework was selected and populated with the factors identified from the review. The review identified 112 factors of relevance. The theory of planned behaviour was selected to guide framework development, organising the framework in terms of the patient’s attitudes about disclosure, perceived pressure to disclose and perceived control over disclosure. Attitudes about disclosure are influenced by a desire to protect oneself or family members, and the patient’s perceptions of relevance of the information for family members, responsibility to disclose, family members’ rights to information and the usefulness of communicating. Perceived pressure to disclose information is shaped by genetic professionals, family members and society. Perceived control over disclosure is affected by family relationships/dynamics, personal communication skills, the ability of the patient and family to understand the information and coping skills of the patient and family member. The family genetic risk communication framework presents a concise synthesis of the evidence on family communication of genetic information; it may be useful in creating and evaluating tools to help genetic counsellors and patients with communication issues.
Electronic supplementary material
The online version of this article (doi:10.1007/s12687-012-0134-9) contains supplementary material, which is available to authorized users.
Genetic risk; Genetic testing; Family communication; Genetic counselling; Complex interventions; Theory of planned behaviour
Perceived risk is a complex concept that influences the genetic counseling process and can affect client coping and behavior. Although the association between family history and risk perception is well recognized in the literature, no studies have explored this relationship specifically in those seeking genetic susceptibility testing for a common chronic condition. REVEAL is a randomized trial assessing the impact of APOE disclosure and genetic risk assessment for Alzheimer’s disease (AD). Using baseline REVEAL data, we hypothesized that there would be a significant association between the degree of AD family history and risk perception of AD, and that this relationship would be stronger in those who believed that genetics is a very important AD risk factor. In our sample of 293 participants, we found that a higher self-perceived risk of AD was associated with strength of family history of AD (p<0.001), belief in genetics as an important AD risk factor (p<0.001), being female (p<0.001) and being Caucasian (p=0.02). These results are the first to demonstrate the association between family history and risk perception in persons volunteering for genetic susceptibility testing for a common complex disease.
Risk perception; Alzheimer’s disease; APOE; Genetic susceptibility testing; Risk assessment
Parent communication of BRCA1/2 test results to minor-age children is an important, yet understudied, clinical issue that is commonly raised in the management of familial cancer risk. Genetic counseling professionals and others who work with parents undergoing this form of testing often confront questions about the risks/benefits and timing of such disclosures, as well as the psychosocial impact of disclosure and nondisclosure on children’s health and development. This paper briefly reviews literature on the prevalence and outcome of parent-child communication surrounding maternal BRCA1/2 test results. It also describes a formative research process that was used to develop a decision support intervention for mothers participating in genetic counseling and testing for BRCA1/2 mutations to address this issue, and highlights the conceptual underpinnings that guided and informed the intervention’s development. The intervention consists of a print-based decision aid to facilitate parent education and counseling regarding if, when, and potentially how to disclose hereditary cancer risk information to children. We conclude with a summary of the role of social, behavioral, and decision science research to support the efforts of providers of familial cancer care regarding this important decision, and to improve the outcomes of cancer genetic testing for tested parents and their nontested children.
parents; children; adolescents; cancer genetic testing; BRCA1/2; decision support; decision aid; family communication
Uptake of genetic testing remains low, even in families with known BRCA1 and BRCA2 (BRCA1/2) mutations, despite effective interventions to reduce risk. We report disclosure and uptake patterns by BRCA1/2-positive individuals to at-risk relatives, in the setting of no-cost genetic counseling and testing.
Relatives of BRCA1/2-positive individuals were offered cost-free and confidential genetic counseling and testing. If positive for a BRCA1/2 mutation, participants were eligible to complete a survey about their disclosure of mutation status and the subsequent uptake of genetic testing by at-risk family members.
One hundred and fifteen of 142 eligible individuals responded to the survey (81%). Eighty-eight (77%) of those surveyed disclosed results to all at-risk relatives. Disclosure to first-degree relatives (FDRs) was higher than to second-degree relatives (SDRs) and third-degree relatives (TDR) (95% vs. 78%; p <0.01). Disclosure rates to male versus female relatives were similar, but reported completion of genetic testing was higher among female versus male FDRs (73% vs. 49%; p<0.01) and SDRs (68% vs. 43%; p<0.01), and among members of maternal versus paternal lineages (63% vs. 0%; p<0.01). Men were more likely than women to express general difficulty discussing positive BCRA1/2 results with at-risk family members (90% vs. 70%; p = 0.03), while women reported more emotional distress associated with disclosure than men (48% vs. 13%; p < 0.01).
We report a very high rate of disclosure of genetic testing information to at-risk relatives. However, uptake of genetic testing among at-risk individuals was low despite cost-free testing services, particularly in men, SDRs, and members of paternal lineages. The complete lack of testing among paternally related at-risk individuals and the lower testing uptake among men signify a significant barrier to testing and a challenge for genetic counselors and physicians working with high-risk groups. Further research is necessary to ensure that family members understand their risk and the potential benefits of genetic counseling.
Patients want to know when errors happen in their care. Professional associations, ethicists, and patient safety experts endorse disclosure of medical error to patients. Surveys of physicians show that they believe harmful errors should be disclosed to patients, yet errors are often not disclosed.
To understand the discrepancy between patients’ expectations and physicians’ behavior concerning error disclosure.
Design, Setting, and Participants
We conducted focus groups to determine what constitutes disclosure of medical error. Twenty focus groups, 4 at each of 5 academic centers, included 204 hospital administrators, physicians, residents, and nurses.
Qualitative analysis of the focus group transcripts with attention to examples of error disclosure by clinicians and hospital administrators.
Clinicians and administrators considered various forms of communication about errors to be error disclosure. Six elements of disclosure identified from focus group transcripts characterized disclosures ranging from Full disclosure (including admission of a mistake, discussion of the error, and a link from the error to harm) to Partial disclosures, which included deferral, misleading statements, and inadequate information to “connect the dots.” Descriptions involving nondisclosure of harmful errors were uncommon.
Error disclosure may mean different things to clinicians than it does to patients. The various forms of communication deemed error disclosure by clinicians may explain the discrepancy between error disclosure beliefs and behaviors. We suggest a definition of error disclosure to inform practical policies and interventions.
error disclosure; ethics; medical mistakes; patient/doctor communication
BRCA genetic test results provide important information to manage cancer risk for patients and their families. Little is known on the communication of genetic test results by mutation status with family members and physicians in the oncology care setting. As part of a longitudinal study evaluating the impact of genetic counseling and testing among recently diagnosed breast cancer patients, we collected patients' self-reported patterns of disclosure. Descriptive statistics characterized the sample and determined the prevalence of disclosure of BRCA test results to family members and physicians. Of 100 patients who completed the baseline and the 6-month followup survey, 77 reported pursuing testing. The majority shared test results with female first-degree relatives; fewer did with males. Participants were more likely to share results with oncologists compared to surgeons, primary care physicians, or other specialty physicians. These findings suggest that while breast cancer patients may communicate results to at-risk female family members and their medical oncologist, they may need education and support to facilitate communication to other first-degree relatives and providers.
Background: Apolipoprotein E (APOE) polymorphisms are unequivocally associated with risk for Alzheimer's disease (AD). It is crucial to understand how this genetic factor affects dementia risk in the general population, as well as in narrowly diagnosed, selected, patient groups.
Methods: We assessed the cross sectional association between APOE genotype and dementia status in a community based sample, the MRC Cognitive Function and Ageing Study (MRC CFAS). In addition, we tested the effects of APOE genotypes on the differences in MMSE scores between the first and third assessment waves (about six years apart), an index of cognitive decline.
Results: The APOE ε4 allele conferred increased risk for dementia (OR=1.5, 95% CI=1.1 to 2.2) compared to ε3 in the MRC CFAS sample. Compared with APOE ε3/ε3 subjects, those with the ε3/ε4 genotypes were not at significantly higher risk for dementia (OR=1.1, 95% CI=0.6 to 1.9), although ε4/ε4 subjects were (OR= 3.8, 95% CI=1.0 to 14.0). Risk estimates were not different between men and women. Notably, our risk estimates for dementia were significantly lower than those reported for a diagnosis of Alzheimer's disease. MMSE scores at wave 3 and the difference in MMSE between baseline and at the third assessment wave were not different across APOE genotypes.
Interpretation: The APOE ε4 allele is a weaker predictor for dementia in the general population than for AD. This may be because dementia can be caused by non-AD pathological processes and because most prevalent dementia occurs at an age when the APOE ε4 effect on AD risk (and therefore dementia) has started to decline.
New genetic tests for adult-onset diseases raise concerns about possible adverse selection in insurance markets. To test for this behavior, 148 cognitively normal individuals participating in a randomized clinical trial of genetic testing for Alzheimer’s disease (AD) were tracked for one year after risk assessment and APOE genotype disclosure. Although no significant differences were found in health, life, or disability insurance purchases, those who tested positive were 5.76 times more likely to have altered their long-term care insurance than individuals who did not receive APOE genotype disclosure. If genetic testing for AD risk assessment becomes common, it could trigger adverse selection in the long-term care insurance market.
The purpose of this study was to examine retrospective reports of rates of HIV disclosure to family and friends over a 15-year time span. Participants included 116 HIV-positive men who have sex with men recruited primarily from an AIDS clinical trials unit associated with a large Midwestern university. Disclosure data were collected on all family members and friends. Results indicated that friends were disclosed to more often than family, but that at any point in time after diagnosis the relative risk of being disclosed to was not statistically significant. Furthermore, neither gender of the family member or friend, race, age at the time of disclosure, level of current satisfaction, nor age of the participant at the time of disclosure significantly influenced disclosure rates over time.
It is known that many mothers rapidly share the results of their BRCA1/2 genetic testing with their children, especially adolescent children. What is less known is the extent to which these mothers may engage fathers in a discussion concerning genetic counseling and the anticipated disclosure of genetic test results to children, or seek shared decision making in this context. This short communication addresses this issue by first examining mothers' and fathers' discussions concerning a research study of family communication. In our view, this conversation likely served as a precursor to, and proxy indicator of, maternal receptivity to partner input regarding the genetic counseling/testing-results disclosure process. We further evaluated how the quality of the parenting relationship is associated with mothers' decisions to include or not include the child's father in this study. Finally, this report addresses potential ways in which the genetic counselor may be able to facilitate parental communication regarding the evolving process of disclosure of genetic information to children and adolescents.
BRCA1/2 testing; cancer; family communication; men; children
To determine whether counseling and support reduces the burden and depressive symptoms of spouse caregivers of Alzheimer’s patients during the institutionalization transition.
A randomized controlled trial of an enhanced counseling and support program for spouse caregivers of persons with Alzheimer’s disease compared to usual care. Structured interviews were conducted with spouse caregivers at baseline, every 4 months during Year 1 and every 6 months thereafter for up to 16 years.
Outpatient research clinic in the New York City metropolitan area.
Referred volunteer sample of 406 spouse caregivers of community-dwelling Alzheimer’s patients enrolled over a 9.5 year period.
Enhanced counseling and support consisting of 6 sessions of individual and family counseling, support group participation and continuous availability of ad hoc telephone counseling.
Outcome measures included burden (modified Zarit Burden Interview) and depressive symptoms (Geriatric Depression Scale).
Burden and depressive symptoms were significantly lower for caregivers in the treatment group when compared to usual care controls at the time of and after institutionalization. Nursing home admission itself significantly reduced burden and depressive symptoms in the intervention and control groups.
Institutionalization alone can reduce caregiver burden and depressive symptoms, but enhanced counseling provides additional long-term benefits. The results offer some of the first clinical evidence for the benefits of enhanced counseling during the transition to institutionalization for Alzheimer’s caregivers.
Caregiving; nursing home placement; nursing home admission; informal long-term care; psychosocial intervention
Background: The increased availability of genetic tests for common, complex diseases, such as Alzheimer's disease (AD), raises questions about what people are willing to pay for these services. Methods: We studied willingness-to-pay for genetic testing in a study of AD risk assessment that included APOE genotype disclosure among 276 first-degree relatives of persons with AD. Results: Seventy-one percent reported that they would ask for such testing from their doctor if it were covered by health insurance, and 60% would ask for it even if it required self-pay. Forty-one percent were willing to pay more than $100 for testing, and more than half would have been willing to pay for the test out of pocket. Participants who learned that they were APOE ɛ4 positive and those who had higher education were less likely to want testing if covered by insurance, possibly to avoid discrimination. Conclusion: This is the first report to examine willingness to pay for susceptibility genetic testing in a sample of participants who had actually undergone such testing. These findings reveal that some participants find valuable personal utility in genetic risk information even when such information does not have proven clinical utility.
Brain alterations in structure and function have been identified in people with risk factors for sporadic type Alzheimer’s disease (AD), suggesting that alterations can be detected decades before AD diagnosis. While the effect of Apolipoprotein E (ApoE) ε4 on the brain is well studied, less is known about the effect of family history of AD. We examined the main effects of family history and ApoE ε4 on brain integrity, in addition to assessing possible additive effects of these two risk factors.
Diffusion tensor imaging was performed in 136 middle-aged asymptomatic participants stratified on family history and ApoE ε4. Mean diffusivity and fractional anisotropy (FA) were entered in factorial analyses to test the effect of AD risk on microstructural brain integrity. We performed a post hoc analysis of the three principle diffusivities (λ1, λ2, λ3) to provide potential additional insight on underlying tissue differences.
Parental family history of AD was associated with lower FA in regions of the brain known to be affected by AD, including cingulum, corpus callosum, tapetum, uncinate fasciculus, hippocampus, and adjacent white matter. Contrary to previous reports there was no main effect of ApoE ε4; however, there was an additive effect of family history and ApoE ε4 where family history positive participants who were also ApoE ε4 carriers had the lowest FA compared to the other groups.
The data indicate that unknown risk factors contained in family history are associated with changes in microstructural brain integrity in areas of the brain known be affected by AD. Importantly, the results provide further evidence that AD pathology may be detected prior to cognitive changes, perhaps decades before disease onset.
Alzheimer’s disease; family history; ApoE ε4; diffusion tensor imaging; MRI; white matter