Shirlene Badger

Psychological, behavioral and social effects of disclosing Alzheimer's disease biomarkers to research participants: a systematic review

BackgroundCurrent Alzheimer’s disease (AD) research initiatives focus on cognitively healthy individuals with biomarkers that are associated with the development of AD. It is unclear whether biomarker results should be returned to research participants and what the psychological, behavioral and social effects of disclosure are. This systematic review therefore examines the psychological, behavioral and social effects of disclosing genetic and nongenetic AD-related biomarkers to cognitively healthy research participants.MethodsWe performed a systematic literature search in eight scientific databases. Three independent reviewers screened the identified records and selected relevant articles. Results extracted from the included articles were aggregated and presented per effect group.ResultsFourteen studies met the inclusion criteria and were included in the data synthesis. None of the identified studies examined the effects of disclosing nongenetic biomarkers. All studies but one concerned the disclosure of APOE genotype and were conducted in the USA. Study populations consisted largely of cognitively healthy first-degree relatives of AD patients. In this group, disclosure of an increased risk was not associated with anxiety, depression or changes in perceived risk in relation to family history. Disclosure of an increased risk did lead to an increase in specific test-related distress levels, health-related behavior changes and long-term care insurance uptake and possibly diminished memory functioning.ConclusionIn cognitively healthy research participants with a first-degree relative with AD, disclosure of APOE ε4-positivity does not lead to elevated anxiety and depression levels, but does increase test-related distress and results in behavior changes concerning insurance and health. We did not find studies reporting the effects of disclosing nongenetic biomarkers and only one study included people without a family history of AD. Empirical studies on the effects of disclosing nongenetic biomarkers and of disclosure to persons without a family history of AD are urgently needed.Trial registrationPROSPERO international prospective register for systematic reviews CRD42016035388. Registered 19 February 2016.

An investigation of the factors effecting high-risk individuals’ decision-making about prophylactic total gastrectomy and surveillance for hereditary diffuse gastric cancer (HDGC)

Hereditary diffuse gastric cancer has an early onset and poor prognosis, therefore, individuals who carry a pathogenic (CDH1) mutation in the E-cadherin gene (CDH1) are offered endoscopic surveillance and advised to undergo prophylactic total gastrectomy (PTG) in their early to mid-twenties. Patients not ready or fit to undergo gastrectomy, or in whom the genetic testing result is unknown or ambiguous, are offered surveillance. Little is known about the factors that influence decisions to undergo or decline PTG, making it difficult to provide optimal support for those facing these decisions. Qualitative interviews were carried out with 35 high-risk individuals from the Familial Gastric Cancer Study in the UK. Twenty-seven had previously undergone PTG and eight had been identified as carrying a pathogenic CDH1 mutation but had declined surgery at the time of interview. The interviews explored the experience of decision-making and factors influencing risk-management decisions. The data suggest that decisions to proceed with PTG are influenced by a number of potentially competing factors: objective risk confirmation by genetic testing and/or receiving a positive biopsy; perceived familial cancer burden and associated risk perceptions; perceptions of post-surgical life; an increasing inability to tolerate endoscopic procedures; a concern that surveillance could miss a cancer developing and individual’s life stage. These findings have implications for advising this patient group.

The Psychosocial Impact of Undergoing Prophylactic Total Gastrectomy (PTG) to Manage the Risk of Hereditary Diffuse Gastric Cancer (HDGC)

Individuals identified as at high risk of developing Hereditary Diffuse Gastric Cancer (HDGC) are advised to undergo prophylactic surgery - have their stomach removed - in their early twenties. Research with (older) cancer patients who undergo gastrectomy for curative reasons suggests that gastric resection has a number of physical and psychosocial sequelae. Because it is difficult to extrapolate the findings of studies of older cancer patients to younger healthy patients who are considering prophylactic total gastrectomy (PTG), the aim of this qualitative interview study was to determine the psychosocial implications of undergoing prophylactic surgery to manage genetic risk. Fourteen men and 13 women from the UK’s Familial Gastric Cancer study who had undergone PTG were invited to participate in qualitative interviews. Most reported that undergoing surgery and convalescence was easier than anticipated. There was evidence that age affected experiences of PTG, with younger patients tending to report faster recovery times and more transient aftereffects. All saw the benefits of risk reduction as outweighing the costs of surgery. Surgery was described as having a range of physical impacts (disrupted appetite, weight loss, fatigue, GI symptoms) that had related psychological, social and economic implications. Those considering PTG need to be aware that its impact on quality of life is difficult to predict and negative sequelae may be ongoing for some individuals.

Perspectives on Communicating Biomarker-Based Assessments of Alzheimer's Disease to Cognitively Healthy Individuals.

In clinical trials which target pathophysiological mechanisms associated with Alzheimer’s disease, research participants who are recruited based on biomarker test results should be informed about their increased risk of developing Alzheimer’s dementia. This paper presents the results of a qualitative focus group study of attitudes and concerns toward learning information about biomarker-based risk status among healthy research participants in the United Kingdom and Spain and people with dementia and their supporters/caregivers from countries represented in the European Working Group of People with Dementia of Alzheimer Europe. The study identified expectations related to learning risk status and preferences related to the content, quality, and follow-up of the disclosure process. The latter emphasize distinctions between risk and diagnoses, the importance of clear information about risk, and suggestions for risk reduction, as well as expectations for follow up and support. The implications of these preferences for practice are discussed. Providing details of research participants’ experience and views may serve as a guide for the development of processes for the responsible disclosure of Alzheimer’s disease biomarkers.

Public perceptions of bacterial whole-genome sequencing for tuberculosis.

The ability to sequence a bacterial genome in less than 1 day represents a step change for clinical microbiology. Genomic data can be used to investigate suspected outbreaks and rapidly to identify multidrug-resistant organisms. We held an open public debate to explore public understanding and perceptions of bacterial whole-genome sequencing (WGS), which we describe here.

High-risk individuals' perceptions of reproductive genetic testing for CDH1 mutations.

Reproductive genetic testing- PreNatal Diagnosis (PND) and Preimplantation Genetic Diagnosis (PGD)—for CDH1 mutations associated with Hereditary Diffuse Gastric Cancer (HDGC)is available in the UK. This qualitative interview study examined high-risk individuals’ (n = 35) views of CDH1 reproductive genetic testing. Interviewees generally regarded reproductive genetic testing as an acceptable form of HDGC risk management. However, some were concerned that their genetic risks required them to plan reproduction and anticipated difficulties communicating this to reproductive partners. Individuals had a preference for PGD over PND because it avoided the need for a termination of pregnancy. However, those who had not yet had children expressed concerns about having to undergo IVF procedures and worries about their effectiveness and the need for embryo selection in PGD. It is suggested that high-risk individuals are provided with access to reproductive genetic counselling.

EXPECTATIONS RELATED TO THE IMPLICATIONS OF LEARNING ALZHEIMER’S DISEASE RISK AMONG COGNITIVELY HEALTHY RESEARCH PARTICIPANTS

CFI1⁄41.000, TLI1⁄41.000, SRMR1⁄40.002, p<0.001. Older persons who were working were less likely to be in Group 2 (b 1⁄4 -1.073, p1⁄4 .003).However, frequency ofparticipatiom in senior activity programmes did not decrease the older person’s predisposition to being more frail and/or cognitively impaired, i.e. Group 2 (b 1⁄4 -0.139, p 1⁄4 .471). Conclusions: In this group of older persons of low SES where the prevalence of CI and physical frailty is high, those who remain working are less likely to be frail and cognitively impaired. This finding validates the value of work as means to preserving cognitive and physical wellness.

Care and Responsibility in Building Futures for Alzheimer’s Disease Research

This chapter considers changes to research practices within contemporary dementia research. It considers how observational cohort studies are being repositioned as a form of promising sociality on which rest expectations of the future of research into Alzheimer’s and other neurodegenerative disorders. Drawing on empirical research with cohort researchers and participants, Milne and Badger argue that taking the sociality of cohorts seriously involves recognising the heterogeneity of actors involved. They suggest that attending to and cultivating attachments between these actors provide the basis for the ‘responsible’ development of research, and argue that the drive to combine and blend studies risks detaching research from these relations and the conditions in which they and data are co-produced.