Bayley, Peter J.

Borson, Soo

Buschke, Herman

Cohen, Donna

Frank, Lori

Wesson, Ashford J.

Scholar Commons | University of South Florida Research

University of South Florida 
Scholar Commons 
Child and Family Studies Faculty Publications Child and Family Studies 
2018 
Genetic Risk of Alzheimer's Disease: Three Wishes Now That the 
Genie Is Out of the Bottle 
Lori Frank 
American Political Science Association Congress 
Ashford J. Wesson 
Stanford University 
Peter J. Bayley 
Stanford University 
Soo Borson 
University of Washington 
Herman Buschke 
Albert Einstein College of Medicine 
See next page for additional authors 
Follow this and additional works at: https://scholarcommons.usf.edu/cfs_facpub 
Scholar Commons Citation 
Frank, Lori; Wesson, Ashford J.; Bayley, Peter J.; Borson, Soo; Buschke, Herman; and Cohen, Donna, 
"Genetic Risk of Alzheimer's Disease: Three Wishes Now That the Genie Is Out of the Bottle" (2018). Child 
and Family Studies Faculty Publications. 11. 
https://scholarcommons.usf.edu/cfs_facpub/11 
This Editorial is brought to you for free and open access by the Child and Family Studies at Scholar Commons. It 
has been accepted for inclusion in Child and Family Studies Faculty Publications by an authorized administrator of 
Scholar Commons. For more information, please contact scholarcommons@usf.edu. 
Authors 
Lori Frank, Ashford J. Wesson, Peter J. Bayley, Soo Borson, Herman Buschke, and Donna Cohen 
This editorial is available at Scholar Commons: https://scholarcommons.usf.edu/cfs_facpub/11 
Journal of Alzheimer’s Disease 66 (2018) 421–423
DOI 10.3233/JAD-180629
IOS Press
421
Editorial
Genetic Risk of Alzheimer’s Disease:
Three Wishes Now That the Genie
is Out of the Bottle
Lori Franka,∗, J. Wesson Ashfordb, Peter J. Bayleyb, Soo Borsonc, Herman Buschked, Donna Cohene,
Jeffrey L. Cummingsf , Peter Daviesg, Margaret Deanh, Sanford I. Finkeli, Lee Hyerj, George Perryk,
Richard E. Powersl and Frederick Schmittm
aHealth and Aging Policy Fellow/American Political Science Association Congressional Fellow; Senior Advisor,
PCORI, Bethesda, MD, USA
bDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA and War Related
Illness and Injury Study Center, VA Palo Alto Health Care System, Palo Alto, CA, USA
cUniversity of Washington School of Medicine, University of Washington, Seattle, WA, USA and University of
Minnesota, Minneapolis, MN, USA
dThe Saul R. Korey Department of Neurology and Dominick P. Purpura Department of Neuroscience, Lena and
Joseph Gluck Distinguished Scholar in Neurology, Albert Einstein College of Medicine, Bronx, NY, USA
eDepartment of Child & Family Studies, College of Behavioral & Community Sciences, University of South
Florida, Tampa, FL, USA
fCenter for Neurodegeneration and Translational Neuroscience, Cleveland Clinic Lou Ruvo Center for Brain
Health, Las Vegas, NY, USA
gLitwin-Zucker Center for Alzheimer’s Disease & Memory Disorders, The Feinstein Institute for Medical
Research, Manhasset, NY, USA
hTexas Tech University Health Sciences Center, Internal Medicine, Amarillo, TX, USA
iDepartment of Psychiatry, University of Chicago Medical School, Chicago, IL, USA
jDepartment of Psychiatry, Mercer School of Medicine, Macon, GA, USA
kBrain Health Consortium, Department Biology and Chemistry, University of Texas at San Antonio, San Antonio,
TX, USA
lDepartments of Pathology and Psychiatry, University of Alabama School of Medicine, Birmingham, AL, USA
mUniversity of Kentucky, Sanders-Brown Center on Aging, Lexington, KY, USA
Handling Editor: Allyson Rosen
Accepted 23 August 2018
Abstract. The availability and increasing popularity of direct-to-consumer genetic testing for the presence of an APOE4
allelle led the Alzheimer’s Foundation of America Medical, Scientific and Memory Screening Advisory Board to identify
three critical areas for attention: 1) ensure consumer understanding of test results; 2) address and limit potential negative
∗Correspondence to: Lori Frank, PhD, Health and Aging Pol-
icy Fellow/American Political Science Association Congressional
Fellow, c/o Alzheimer’s Foundation of America, 322 Eighth
Avenue, Fl 7, New York NY 10001, USA. Tel.: +1 866 232 8484;
E-mail: LoriBFrank@gmail.com.
ISSN 1387-2877/18/$35.00 © 2018 – IOS Press and the authors. All rights reserved
This article is published online with Open Access and distributed under the terms of the Creative Commons Attribution Non-Commercial License (CC BY-NC 4.0).
422 L. Frank et al. / Genetic Risk of Alzheimer’s Disease: Three Wishes Now That the Genie is Out of the Bottle
consequences of acquiring this information; and 3) support linking results with positive health behaviors, including potential
clinical trial participation. Improving access to appropriate sources of genetic counseling as part of the testing process is
critical and requires action from clinicians and the genetic testing industry. Standardizing information and resources across the
industry should start now, with the input of consumers and experts in genetic risk and health information disclosure. Direct-
to-consumer testing companies and clinicians should assist consumers by facilitating consultation with genetic counselors
and facilitating pursuit of accurate information about testing.
Keywords: APOE, genetic risk, genetic testing, late-onset Alzheimer’s disease
Commercially available direct-to-consumer
genetic testing is now a reality, and as of April
2017 consumers could learn their apolipoprotein
E4 (APOE4) genotype, which is an established
risk factor for Alzheimer’s disease and one of the
strongest genetic factors linked with a disease pro-
cess. With this newly available testing, consumers
get information about risk, a probability about
future outcome. However, consumer understanding
of the meaning and implications of genetic test
results is limited, as is the understanding by many
physicians, largely due to lack of attention to this
vital area in medical school curricula. Nonetheless,
the genetic genie is out of the bottle, preempting
debates about advisability and making identification
of ways to address the very real needs associated
with direct-to-consumer testing paramount.
Historical examples of disease disclosure offer a
brief course in medical paternalism, from debates
about sharing cancer diagnoses in the 1960s, to con-
cerns about disclosure of HIV infection in the 1990s
and later home testing and controversies about dis-
closure of genetic predisposition for disorders such as
Huntington’s disease in which disease development
is more specifically determinable than late-onset
Alzheimer’s disease (LOAD) [1–3]. Patient and con-
sumer access to health-related information about
themselves is expected to increase, and such access
is consistent with increased emphasis on patient-
empowerment and shared medical decision-making
[4, 5]. Clinical wisdom is required as a guide to med-
ical decisions, but the patient role is now understood
as appropriately primary and autonomous.
Given increasing availability of genetic testing for
risk of LOAD, there are three goals for optimizing this
type of genetic testing (see https://alzfdn.org/gene
testing/).
The first goal is to ensure that consumers under-
stand the meaning of test results. For APOE genes,
understanding that a measure of risk is not a clinical
diagnosis is a crucial point. As important is convey-
ing that “negative” results do not confer protection
against development of the disorder at a later time.
Beyond APOE, there are at least 20 other genetic
factors which have been shown to have a small but
significant role in determining Alzheimer risk. Such
information can and should be used by individuals
and families in making plans for their future lives.
Understanding of genetic test results also requires
attention to the potential for inaccurate results.
The second goal is to limit negative consequences
that result from acquiring new genetic information.
Stories continue to appear in the popular press and
social media about individuals who learn details
about themselves and their families from genetic
testing that cause upset or harm—surprises about
true paternity, for example. Disclosure of infor-
mation about risk of LOAD may have negative
consequences [6]. Given the current limitations in
disease modification, the absence of effective treat-
ments, and the distressing outcomes for individuals
with dementia and their families—concerns about
negative consequences following a test result are
not unfounded and should be taken seriously and
addressed.
The third goal is that, at both the individual- and
the population-level, results should be used to inform
and support adoption and maintenance of lifestyle
modifications that may reduce overall risk for LOAD.
Evidence is suggestive, but not definitive, that these
interventions can alter the age of dementia onset by
several years (e.g., [7]). Increased participation in rel-
evant clinical research studies is another public health
outcome that can be supported through provision of
information about risk.
With these goals in mind, what is the best setting
and what are optimal methods to support appropri-
ate understanding and use of genetic information,
including mitigating the potential negative emotional
impact?
Some suggest that the physician’s office is the
only appropriate venue for learning these results.
While physicians certainly could provide appropriate
guidance about risk and offer insights into treatment
L. Frank et al. / Genetic Risk of Alzheimer’s Disease: Three Wishes Now That the Genie is Out of the Bottle 423
options, the reality is that most clinicians lack the
training and report feeling ill equipped to address
genetic test results [8]. Limited training may result
in a wide variation in the information and coun-
seling provided, further reducing the value of the
office consultation. Given the rapidly growing use
of genetic testing, training in conveying and explain-
ing the genetic test results should be included in the
education of health professionals. This training can
address when referral to genetic counseling is appro-
priate.
Consumers are receiving results at home, with the
information provided by commercial entities offer-
ing the testing reviewed in the US by the FDA under
regulation of medical devices. The value of the infor-
mation to meet the goals described above has yet to
be determined. There are viable paths for consumers
to optimize their own experience without a visit to a
clinician, or in addition to such a visit. Increasingly,
consumer-led online communities are available as a
source of support and some guidance to those learn-
ing of a risk of younger onset of LOAD. Inclusion
of clinicians and genetic counselors in these forums
can enhance the quality of the guidance provided and
improve understanding of the meaning of increased
risk.
As more biomarkers associated with dementia and
other diseases and conditions are identified, ongo-
ing research will be increasingly needed to inform
improvements in how consumers obtain and use
information about risk, as well as the benefits and
harms of learning personal genetic information. The
priority now is to ensure the availability of resources
for understanding genetic risk information, reduce
avoidable negative impacts of this information and
advance ways that the information can be used to
support individual and population health. Improving
access to appropriate sources of genetic counseling
as part of the testing process is critical, as is avoiding
inappropriate disclosure of confidential information.
Protections for consumers who learn their genetic
risk, including with health insurance, long term care
insurance, and life insurance, must be clear. Devel-
oping and standardizing systems for information and
resource management across the industry should start
now, with the input of consumers and experts in
genetic risk and health information disclosure. Con-
sumers should be encouraged to consult with genetic
counselors as part of their decision to discover their
genetic make-up, by clinicians they may consult prior
to testing, and by the direct-to-consumer testing com-
panies themselves. The genie is out of the bottle; with
the right information consumers can be the recipients
of the benefit.
ACKNOWLEDGMENTS
The authors thank the Alzheimer’s Foundation
of America for facilitating discussion of the issues
addressed here, as well as Carr Smith, PhD and Qi
Wang, MD for helpful comments on this statement.
Authors’ disclosures available online (https://
www.j-alz.com/manuscript-disclosures/18-0629r2).
DISCLAIMERS
This viewpoint is based on the Alzheimer’s Foun-
dation of America Medical, Scientific and Memory
Screening Advisory Board statement on genetic
screening. All authors are members of the AFA Advi-
sory Board. The views expressed in this article are the
authors’ and do not represent an official position of
the authors’ institutions.
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