Statement of the Alzheimer’s Foundation of America (AFA) and AFA’S Medical, Scientific and Memory Screening Advisory Board on Genetic Testing to Determine Risk of Alzheimer’s Disease
Genetic testing, including testing for one’s risk for Alzheimer’s disease (AD), is becoming increasingly available. To guide optimal use of this important innovation, the Alzheimer’s Foundation of America (AFA) identifies issues that need to be considered in the decision to obtain genetic testing for late onset AD risk. Before deciding to request genetic testing to determine risk of late onset AD, it is important for individuals to understand the benefits, limitations and other implications of learning this personal genetic health information.
Guidance to consumers is provided by commercial genetic testing firms but there are no industry-wide standards for this information, and thus far the U .S. Food and Drug Administration (FDA) statement on communicating about AD genetic risk is limited to the to the one commercial firm offering this testing.
Recognizing the level of public interest in genetic testing for late onset Alzheimer’s disease, AFA and its Medical, Scientific and Memory Screening Advisory Board (the Advisory Board) is recommending standardization of consumer information included with test kits by providers of this genetic testing. AFA and the Advisory Board is also calling on consumers to develop a thorough understanding of the risks and benefits associated with such testing. Further, AFA and its Advisory Board recommends that new studies be conducted into how dissemination of such genetic information can impact, beneficially or adversely, an individual’s emotional and mental well-being, adoption of lifestyle modifications, and future planning. It is important for people undergoing genetic testing to understand that genes can be shared by family members, and thus genetic information for one may have implications for others beyond the individual choosing to be tested.
On April 6, 2017 the FDA approved a commercial enterprise to market a Genetic Health Risk (GHR) kit to test for, among other items, late onset AD risk. Using DNA from a saliva sample, the kit yields a report on consumer Apolipoprotein-E ε4 (APOEε4) allele status (zero, one or two copies). Possession of one APOEε4 allele increases the risk of developing late onset Alzheimer’s disease by 3 to 5-fold, and possession of two APOEε4 alleles increases risk 15 to 20-fold.
APOE genotype accounts for the clear majority of AD genetic risk. The finding of a relationship between AD and APOE genotype has been widely replicated, yet it has long been controversial as to whether to disclose such genetic information to individuals who are seeking this information. Numerous risks or harms, as well as benefits, have been considered.
Individuals may wrongly confuse genetic risk with genetic certainty. ApoE4 confers higher probability of developing AD, but does not by itself cause the disease – many individuals who are apoE4 positive never develop AD in their lifetime.
The distinction between risk and causation must be made clear to consumers. Genetic information may be used to negatively impact individuals trying to purchase certain insurance products. While the current Genetic Information Nondiscrimination Act (GINA) offers some protections, in a few states, long-term care insurance and life insurance companies still have the right to ask if an individual knows their own genetic information and adjust long-term care insurance premiums accordingly. Therefore, the ways in which personal health information—including genetic status—could be used has important implications, posing risks to consumers for which they would have little control.
In addition, genetic information may also be subject to involuntary disclosure through computer hacking or other security breaches. As with a person’s social security number, a person’s genetic information will need to be vigilantly safeguarded from those seeking the information for exploitative or criminal purposes.
Risks of disclosure extend to families, as well. Because genes are shared among family members, discovering one individual’s genotype may have implications for children and siblings. There has been insufficient attention directed toward understanding the hazards of receiving unsolicited genetic information about a first-degree relative and how that information can impact one’s own health care decisions and psychosocial well-being.
While anecdotal cases of harm associated with learning one’s APOE genotype cannot be dismissed, a 2006 analysis revealed no increase in depression, anxiety, suicidal ideation, or completed suicide in individuals to whom this information was disclosed, relative to those to whom it was not. While there was a transient increase in distress in those learning that they were positive for APOE-ε4, there were no clinically significant effects. Given the greater access to genetic testing today, a study to examine whether such findings still apply – over a broader cross-section of consumers – is warranted.
Individuals who undergo testing and become aware of their own genotype may take positive, pro-active steps to plan for and optimize their future lives, and may benefit from early detection. Several modifiable factors have been associated with a reduced risk for developing late onset AD, though not all are universally accepted and clear cause-and-effect relationships have not been fully established. These factors include use of cholesterol-lowering drugsand nonsteroidal anti-inflammatory drugs (NSAIDS), higher education levels, healthy diet, and exercise, particularly if intense enough to increase brain-derived neurotrophic factor (BDNF).
Direct evidence of the positive effect on cognition of a select group of lifestyle and medical interventions has led to the suggestion that AD risk reduction is possible.
Those with normal cognition and a genetic predisposition for AD can also enroll and participate in clinical trials aimed at preventing or delaying the onset of AD-related symptoms.
AFA and AFA’s Medical, Scientific and Memory Screening Advisory Board call on companies offering genetic testing for AD to adopt industry-wide standards that provide easy access and/or referrals to appropriate information, resources and qualified genetic counseling professionals as part of the testing process. It is critical that consumers are armed with an understanding of genetic risk information, prior to receiving a related test result. Pre- and post-test information for consumers should also be standardized across the industry with expert consensus on content. Including consumers in this information vetting process could enhance usability and is highly recommended. In addition, consumers should take the time to obtain information and education about genetic testing prior to making their decision to discover their genetic risk of disease. Ideally consumers would seek out formal genetic counseling as well. We would also advise consumers take the time to obtain information and education about genetic testing prior to making their decision to discover their genetic risk of disease.
With increased consumer interest and greater availability of testing, millions of Americans are now being tested. Positive and negative consequences of processing genetic information should be considered by all concerned. Such advanced information has the potential to benefit both individuals and the population, but only if it is accurately conveyed and understood.
As a broader consumer base is being presented with their APOE profile, AFA calls on researchers to revisit past analysis of APOE genetic disclosure and conduct new research on how such information can influence both positive and negative outcomes, including lifestyle changes and future planning steps as well as stress, depression, anxiety, suicidal ideation, and suicide among individuals to whom this information is disclosed. Such a study should encompass a broad cross-section of Americans, including diverse ethnic, racial, gender, education, geographic and socio-economic groups. It should address the development of protocols for pre- and post-testing counseling and risk management, to safeguard the consumers, ensure responsible use of genetic information, and mitigate the potential risks of unauthorized or otherwise harmful disclosure while optimizing the benefits of such information.
Both AFA and the members of AFA’s Medical, Scientific and Memory Screening Advisory Board recognize the growing importance of genetics in Alzheimer’s disease diagnosis, as well as the emergence of personalized medicine, which may be able to effectively target therapies to affected individuals at some point. In addition, advances in testing, and the availability of detailed genetic information as part of a person’s health care records, will increase the importance of genetic testing and the potential impact such information has in promoting behavior modification or preventive strategies for chronic conditions such as Alzheimer’s disease. As a result, AFA and its Medical, Scientific and Memory Screening Advisory Board will continue to examine the role of genetic testing, its impact on health consumers and ways to ensure that consumers understand the results of a genetic test and what safeguards can be used to assure appropriate use of such information.
 The Alzheimer’s Foundation of America (AFA) is a New York based national nonprofit organization that unites more than 2,600 member organizations nationwide with the goal of providing optimal care and services to individuals confronting dementia, and to their caregivers and families. AFA’s President and CEO is Charles J. Fuschillo, Jr. and Bert E. Brodsky is Chair of AFA’s Board of Trustees.
 Members of AFA’s Medical, Scientific and Memory Screening Advisory Board are (in alphabetical order) : J. Wesson Ashford, M.D., Ph.D. Director, War Related Illness and Injury Study Center (WRIISC), VA Palo Alto Health Care System; Peter J. Bayley, Ph.D., War Related Illness and Injury Study Center (WRIISC). VA Palo Alto Health Care System; Her Soo Borson MD, Professor Emerita, University of Washington School of Medicine, Affiliate Professor, School of Nursing, and Dementia Care Research and Consulting; Herman Buschke, M.D., Albert Einstein College of Medicine; Donna Cohen, Ph.D. Professor, College of Behavioral & Community Sciences (CBCS), University of South Florida (USF); Jeffrey L. Cummings, M.D., Sc.D. Director, Cleveland Clinic Lou Ruvo Center for Brain Health Director, Center for Neurodegeneration and Translational Neuroscience Professor, Cleveland Clinic Lerner College of Medicine; Peter Davies, PhD Director, Litwin-Zucker Center for Alzheimer’s Disease & Memory Disorders, The Feinstein Institute for Medical Research; Margaret Dean, R.N., C.S.-B.C., N.P.-C., M.S.N., F.A.A.N.P. Texas Tech Health Sciences Center, Geriatric Division, Texas Tech University Health Sciences Center; Sanford I. Finkel M.D., University of Chicago Medical School, Clinical Professor of Psychiatry; Lori Frank, Ph.D, Health and Aging Policy Fellow; Leon (Lee) Hyer, Ph,D. Professor, Mercer Medical School at Georgia Neurosurgical Institute; George Perry, Ph.D., Dean and Professor Semmes Foundation Distinguished University Chair in Neurobiology College of Sciences, The University of Texas at San Antonio; Richard E. Powers, M.D., Professor, University of Alabama at Birmingham School of Medicine; Frederick A. Schmitt, Ph.D., Professor Sanders-Brown Center on Aging, University of Kentucky.
 CNBC, Amazon has suddenly become a big marketplace for selling genetic tests, (Nov. 21, 2017)(www.cnbc.com/2017/11/21/amazon-has-suddenly-become-a-big-marketplace-for-selling-genetic-tests.html).
 FDA Press Release, FDA allows marketing of first direct-to-consumer tests that provide genetic risk information for certain condition (April 6, 2017) (www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm551185.htm).
 National Academies of Sciences, Engineering, and Medicine, Preventing cognitive decline and dementia: A way forward (2017)(https://doi.org/10.17226/24782); see also, The JAMA Network, Effect of the Apolipoprotein E Genotype on Cognitive Change During a Multidomain Lifestyle Intervention (Jan. 18, 2018) (https://jamanetwork.com/journals/jamaneurology/article-abstract/2670443?redirect=true).
 FDA Press Release, April 6, 2017 (www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm551185.htm).
 Raber J, Huang Y, Ashford JW, ApoE genotype accounts for the vast majority of AD risk and AD pathology (May-Jun. 2004)(www.ncbi.nlm.nih.gov/pubmed/15172743).
 Id. APOE is not the only risk factor for Alzheimer’s disease, however. Mutations to the TREM2 and SORL1 genes have also been linked to disease. See, AlzForum, New Evidence Confirms TREM2 Binds Aβ, Drives Protective Response (19 Apr 2017); Liu F, Ikram MA, Janssens AC, et. al., A study of the SORL1 gene in Alzheimer’s disease and cognitive function. J Alzheimers Dis. 2009;18(1):51-64.
 The Genetic Information Nondiscrimination Act of 2008 (Pub. L. 110–233, 122 Stat. 881, enacted May 21, 2008) is an Act of Congress in the United States designed to prohibit some types of genetic discrimination. The act bars the use of genetic information in health insurance and employment: it prohibits group health plans and health insurers from denying coverage to a healthy individual or charging that person higher premiums based solely on a genetic predisposition to developing a disease in the future, and it bars employers from using individuals’ genetic information when making hiring, firing, job placement, or promotion decisions.
 The Risk Evaluation and Education for Alzheimer’s Disease (REVEAL) Study, The Health Behavior and Health Education (HBHE) Genetics Research Group, Univ. of Michigan (http://hbhegenetics.sph.umich.edu/research-project/risk-evaluation-and-education-alzheimers-disease-study).
 Green, R., Roberts, J., Cupples, L. et. al., Disclosure of APOE Genotype for Risk of Alzheimer’s Disease, N Engl J Med 2009; 361:245-254 (July 16, 2009)(www.nejm.org/doi/full/10.1056/nejmoa0809578#t=article).
 Some research on the impact of direct to consumer APOE genetic testing is already being conducted. See, Zallen DT, “Well, good luck with that”: reactions to learning of increased genetic risk for Alzheimer disease, Genet Med. (Mar 8, 2018) (www.nature.com/articles/gim201813) which concluded, “APOE testing did produce adverse psychological reactions in many participants.”
 Zissimopoulos, J. M., D. Barthold, et al. (2017), Sex and Race Differences in the Association Between Statin Use and the Incidence of Alzheimer Disease JAMA Neurol 74(2): 225-232 (www.ncbi.nlm.nih.gov/pubmed/27942728).
Imbimbo, B. P., V. Solfrizzi, et al. (2010), Are NSAIDs useful to treat Alzheimer’s disease or mild cognitive impairment?, Front Aging Neurosci 2 (www.ncbi.nlm.nih.gov/pubmed/20725517).
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 Ngandu T, Lehtisalo, et. al., A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomized controlled trial, Lancet. 2015 Jun 6; 385 (9984):2255-63 (www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)60461-5/abstract).
 See Besser et al., Factors Affecting Recall of Different Types of Personal Genetic Information about Alzheimer’s Disease Risk: The REVEAL Study (Jan. 16, 2016) (www.ncbi.nlm.nih.gov/pmc/articles/PMC4470386/pdf/nihms-645971.pdf).
 The National Society of Genetic Counselors (NSGC) promotes the professional interests of genetic counselors and provides a network for professional communications. NSGC has a database of genetic counselors that can be accessed at: https://www.nsgc.org/findageneticcounselor.
 See, MIT Technology Review, 2017 was the Year Consumer DNA Testing Blew Up (February 12, 2018) “The number of people who have had their DNA analyzed with direct-to-consumer genetic genealogy tests more than doubled during 2017 and now exceeds 12 million, according to industry estimates.” (www.technologyreview.com/s/610233/2017-was-the-year-consumer-dna-testing-blew-up/).
 See, Green, R., Roberts, J., Cupples, L. et. al., Disclosure of APOE Genotype for Risk of Alzheimer’s Disease, N Engl J Med 2009; 361:245-254 (July 16, 2009)(www.nejm.org/doi/full/10.1056/nejmoa0809578#t=article), and Marteau TM, French DP, et. al. Effects of communicating DNA-based disease risk estimates on risk-reducing behaviours, Cochrane Database Syst Rev. Oct. 6, 2010 (www.ncbi.nlm.nih.gov/pubmed/20927756).