GeneMatch: A novel recruitment registry using at-home APOE genotyping to enhance referrals to Alzheimer's prevention studies.

INTRODUCTION: Recruitment for Alzheimer's disease (AD) prevention research studies is challenging because of lack of awareness among cognitively healthy adults coupled with the high screen fail rate due to participants not having a genetic risk factor or biomarker evidence of the disease. Participant recruitment registries offer one solution for efficiently and effectively identifying, characterizing, and connecting potential eligible volunteers to studies. METHODS: Individuals aged 55-75 years who live in the United States and self-report not having a diagnosis of cognitive impairment such as MCI or dementia are eligible to join GeneMatch. Participants enroll online and are provided a cheek swab kit for DNA extraction and apolipoprotein E (APOE) genotyping. Participants are not told their APOE results, although the results may be used in part to help match participants to AD prevention studies. RESULTS: As of August 2018, 75,351 participants had joined GeneMatch. Nearly 30% of participants have one APOE4 allele, and approximately 3% have two APOE4 alleles. The percentages of APOE4 heterozygotes and homozygotes are inversely associated with age (P < .001). DISCUSSION: GeneMatch, the first trial-independent research enrollment program designed to recruit and refer cognitively healthy adults to AD prevention studies based in part on APOE test results, provides a novel mechanism to accelerate prescreening and enrollment for AD prevention trials.

Alzheimer's Prevention Initiative Generation Program: Development of an APOE genetic counseling and disclosure process in the context of clinical trials.

INTRODUCTION: As the number of Alzheimer's disease (AD) prevention studies grows, many individuals will need to learn their genetic and/or biomarker risk for the disease to determine trial eligibility. An alternative to traditional models of genetic counseling and disclosure is needed to provide comprehensive standardized counseling and disclosure of apolipoprotein E (APOE) results efficiently, safely, and effectively in the context of AD prevention trials. METHODS: A multidisciplinary Genetic Testing, Counseling, and Disclosure Committee was established and charged with operationalizing the Alzheimer's Prevention Initiative (API) Genetic Counseling and Disclosure Process for use in the API Generation Program trials. The objective was to provide consistent information to research participants before and during the APOE counseling and disclosure session using standardized educational and session materials. RESULTS: The Genetic Testing, Counseling, and Disclosure Committee created a process consisting of eight components: requirements of APOE testing and reports, psychological readiness assessment, determination of AD risk estimates, guidance for identifying providers of disclosure, predisclosure education, APOE counseling and disclosure session materials, APOE counseling and disclosure session flow, and assessing APOE disclosure impact. DISCUSSION: The API Genetic Counseling and Disclosure Process provides a framework for large-scale disclosure of APOE genotype results to study participants and serves as a model for disclosure of biomarker results. The process provides education to participants about the meaning and implication(s) of their APOE results while also incorporating a comprehensive assessment of disclosure impact. Data assessing participant safety and psychological well-being before and after APOE disclosure are still being collected and will be presented in a future publication.