Emotional responses to APO E genotype disclosure for Alzheimer disease.

Department of Family Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, 87131, USA.
Journal of Genetic Counseling (Impact Factor: 1.75). 05/2005; 14(2):141-50. DOI: 10.1007/s10897-005-4063-1
Source: PubMed

ABSTRACT The purpose of our study is to assess the emotional responses to disclosing APO E genotype to asymptomatic older adults at increased risk for Alzheimer disease (AD). This is a longitudinal cohort study of volunteer subjects who were aged 50 years or over, asymptomatic for (AD), had a family history of AD, passed a psychological assessment, and participated in pre- and post-test genetic counseling and three follow-up visits over 10 months. We analyzed responses by three emotional constructs: depressed, worried, and relieved. Three hundred and twenty-eight subjects were screened, 76 received their APO E genotype. When emotional responses occurred it was immediate, between baseline and the 1 month follow-up. Emotional reactions did not change significantly past 1 month. Our results suggest that for emotionally stable persons, disclosing results of their APO E genotype, high risk subjects did not report more depression or worry and low risk subjects felt relieved by knowing the results. Future studies should evaluate the risks of disclosure to family members involved in the diagnostic work-up of a relative and include subjects from a broader range of emotional stability and socioeconomic background.

  • [Show abstract] [Hide abstract]
    ABSTRACT: With increased frequency, clinical geneticists are asked for genetic advice on the heredity of dementia in families. Alzheimer's disease is in most cases a complex disease, but may be autosomal dominant inherited. Mutations in the PSEN1 gene are the most common genetic cause of early onset Alzheimer's disease, whereas APP and PSEN2 gene mutations are less frequent. Familial frontotemporal dementia may be associated with a mutation in the MAPT or GRN gene, or with a repeat expansion in the C9orf72 gene. All these genes show autosomal dominant inheritance with a high penetrance. Although Alzheimer's disease and frontotemporal dementia are clinically distinguishable entities, phenotypical overlap may occur. Rarely, dementia is caused by mutations in other autosomal dominant genes or by genetic defects with autosomal recessive, X-linked dominant or mitochondrial inheritance. The inherited forms of frontotemporal dementia and Alzheimer's disease show a large phenotypic variability also within families, resulting in many remaining uncertainties for mutation carriers. Therefore, genetic counseling before performing genetic testing is essential in both symptomatic individuals and healthy at risk relatives. This review provides an overview of the genetic causes of dementia and discusses all aspects relevant for genetic counseling and testing. Furthermore, based on current knowledge, we provide algorithms for genetic testing in patients with early onset Alzheimer's disease or frontotemporal dementia.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 09/2012; 159B(6):628-43. DOI:10.1002/ajmg.b.32080 · 3.27 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Alzheimer disease (AD) is a genetically heterogenous disorder; in rare cases autosomal dominantly inherited mutations typically cause early-onset familial AD (EOAD), whereas the risk for late-onset AD (LOAD) is generally modulated by genetic variants with relatively low penetrance but high prevalence, with variants in apolipoprotein E (APOE) being a firmly established risk factor. This article presents an overview of the current literature on the psychological and behavioral impact of genetic testing for AD. The few studies available for presymptomatic testing for EOAD showed that only a very small proportion of individuals had poor psychological outcomes as a result. Initial interest in testing for EOAD decreases significantly after identification of a specific mutation in a kindred, suggesting that interest and potential for knowledge may not translate into actual testing uptake. The majority of individuals from both the general population and those with a family history of AD had positive attitudes towards, and were interested in, susceptibility testing for APOE. Motivations for genetic testing included to provide information for future planning and to learn about one's own and one's children's risks of developing AD. Although susceptibility testing for APOE genotype is not currently recommended due to the lack of clinical utility, this review demonstrates that there is interest in testing and no obvious adverse psychological effects to those who have been tested.
    Genetic Testing and Molecular Biomarkers 06/2012; 16(8):935-42. DOI:10.1089/gtmb.2011.0300 · 1.44 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: As the genetics of neurodegenerative disease become better understood, opportunities for genetic susceptibility testing for at-risk individuals will increase. Such testing raises important ethical and practice issues related to test access, informed consent, risk estimation and communication, return of results, and policies to prevent genetic discrimination. The advent of direct-to-consumer genetic susceptibility testing for various neurodegenerative disorders (including Alzheimer's disease, Parkinson's disease, and certain prion diseases) means that ethical and practical challenges must be faced not only in traditional research and clinical settings, but also in broader society. This review addresses several topics relevant to the development and implementation of genetic susceptibility tests across research, clinical, and consumer settings; these include appropriate indications for testing, the implications of different methods for disclosing test results, clinical versus personal utility of risk information, psychological and behavioral responses to test results, testing of minors, genetic discrimination, and ethical dilemmas posed by whole-genome sequencing. We also identify future areas of likely growth in the field, including pharmacogenomics and genetic screening for individuals considering or engaged in activities that pose elevated risk of brain injury (e.g., football players, military personnel). APOE gene testing for risk of Alzheimer's disease is used throughout as an instructive case example, drawing upon the authors' experience as investigators in a series of multisite randomized clinical trials that have examined the impact of disclosing APOE genotype status to interested individuals (e.g., first-degree relatives, persons with mild cognitive impairment).
    Progress in Neurobiology 04/2013; 110. DOI:10.1016/j.pneurobio.2013.02.005 · 10.30 Impact Factor