- The Risk Evaluation and Education for Alzheimer's Disease (REVEAL) Study is an ongoing series of multi-site randomized controlled trials that provide empirical data to address ethical, social and translational issues in genetic susceptibility testing for common diseases. Such work has become increasingly important given the expansion of genome-wide association studies identifying genetic risk factors for common diseases and corresponding efforts to commercialize genetic testing using these markers. Our paradigm for these trials is disclosure of Apolipoprotein E (APOE) genotype as part of risk assessment for Alzheimer's disease (AD) to unaffected individuals. In previous funding cycles we have enrolled 1000 participants in three separate trials, and our multi-disciplinary team has been highly productive in analyzing many aspects of the psychological impact and health behavior changes of receiving genetic risk information. We now propose the first translational genetics study to focus upon the situation where mild early symptoms of a disease (phenotype) and known genetic marker (genotype) information can be used together to produce more imminent risk projections. To do this, we will develop genotype specific risk curves for patients with Mild Cognitive Impairment, a condition where the APOE epsilon 4 allele is associated with more rapid progression to AD and differential response to certain pharmacological treatments. We will carry out a new randomized clinical trial to examine the impact of """"""""imminent risk assessment"""""""" (i.e., risk of conversion to AD within 3 years) in these individuals and their care partners. We also propose to develop and validate a novel instrument, which we call the Capacity Assessment Tool for Genetic Testing, to reliably assess an individual's capacity to consent to genetic testing, which will be useful for clinicians and researchers working with neuropsychiatric diseases. Finally, we propose to systematically study the long-term psychological impact and health behavior changes in participants who learned their APOE genotype in earlier cycles of the REVEAL Study, some of whom were enrolled as early as 2000. These data will help inform policy and practice regarding the use of genetic risk information for common, complex diseases. Public Health Relevance: REVEAL IV Project Narrative: In this continuation of the REVEAL Study, we will conduct a new randomized clinical trial to determine the psychological and health behavior changes associated with disclosing APOE genotype and 3-year risk estimates to persons with mild memory problems. We will also create a new instrument that clinicians and researchers can use to reliably evaluate a patient's capacity to consent to genetic testing and examine long-term impact of genetic risk assessment by following REVEAL Study patients 2-10 years following disclosure.

Public Health Relevance

In this continuation of the REVEAL Study, we will conduct a new randomized clinical trial to determine the psychological and health behavior changes associated with disclosing APOE genotype and 3-year risk estimates to persons with mild memory problems. We will also create a new instrument that clinicians and researchers can use to reliably evaluate a patient's capacity to consent to genetic testing and examine long-term impact of genetic risk assessment by following REVEAL Study patients 2-10 years following disclosure.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project (R01)
Project #
7R01HG002213-11
Application #
8147864
Study Section
Ethical, Legal, and Social Implications of Human Genetics Study Section (ELS)
Program Officer
Mcewen, Jean
Project Start
1999-09-30
Project End
2013-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
11
Fiscal Year
2011
Total Cost
$596,485
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
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Guan, Yue; Roter, Debra L; Wolff, Jennifer L et al. (2017) The impact of genetic counselors' use of facilitative strategies on cognitive and emotional processing of genetic risk disclosure for Alzheimer's disease. Patient Educ Couns :
Guan, Yue; Roter, Debra L; Erby, Lori H et al. (2017) Disclosing genetic risk of Alzheimer's disease to cognitively impaired patients and visit companions: Findings from the REVEAL Study. Patient Educ Couns 100:927-935
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Besser, Andria G; Sanderson, Saskia C; Roberts, J Scott et al. (2015) Factors affecting recall of different types of personal genetic information about Alzheimer's disease risk: the REVEAL study. Public Health Genomics 18:78-86
Carere, Deanna Alexis; VanderWeele, Tyler; Moreno, Tanya A et al. (2015) The impact of direct-to-consumer personal genomic testing on perceived risk of breast, prostate, colorectal, and lung cancer: findings from the PGen study. BMC Med Genomics 8:63
Ostergren, Jenny E; Gornick, Michele C; Carere, Deanna Alexis et al. (2015) How Well Do Customers of Direct-to-Consumer Personal Genomic Testing Services Comprehend Genetic Test Results? Findings from the Impact of Personal Genomics Study. Public Health Genomics 18:216-24
Green, Robert C; Christensen, Kurt D; Cupples, L Adrienne et al. (2015) A randomized noninferiority trial of condensed protocols for genetic risk disclosure of Alzheimer's disease. Alzheimers Dement 11:1222-30

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