ARTICLE

Patients’ views on the ethical challenges of early

Parkinson disease detection
Eva Schaeffer, MD,* Annette Rogge, MD,* Katharina Nieding, Vera Helmker, Christa Letsch, Correspondence
Björn Hauptmann, MD, and Daniela Berg, MD Dr. Schaeffer

®
eva.schaeffer@uksh.de
Neurology 2020;94:e2037-e2044. doi:10.1212/WNL.0000000000009400

Abstract
Objective
To evaluate the point of view of patients with Parkinson disease (PD) on early detection and
risk disclosure in the prodromal phase of PD and to derive recommendations for an ethical
framework for the recruitment of prodromal PD cohorts.

Methods
A standardized questionnaire to evaluate the patients’ perception on early diagnosis in PD was
designed by an interdisciplinary study group. After testing in a preliminary feasibility study (n =
20), the survey was performed retrospectively with patients from our clinic.

Results
A total of 101 patients with PD answered the questions. The majority of patients reported that
time from onset of motor symptoms to diagnosis was burdensome, including false diagnoses
and many consultations of various medical specialists. However, most of the patients evaluated
early risk disclosure with skepticism. Freedom of choice and the potential of changes in lifestyle
were rated as important.

Conclusion
Although patients with PD reported the time to diagnosis retrospectively as burdensome, the
majority was skeptical regarding early disclosure of risk, especially with regard to the lack of
pharmacologic options. Circumstances under which early detection and disclosure would have
been approved by the majority of patients were (1) advice on lifestyle changes (exercise,
nutrition) as potentially disease course–modifying therapy; (2) the establishment of an early
diagnosis “culture,” including early clarification of the patients’ wish to know; and (3) regular
support and follow-up of individuals after risk disclosure.

*These authors contributed equally to this work.

From the Department of Neurology (E.S., K.N., V.H., D.B.) and Institute of Experimental Medicine, Medical Ethics (A.R.), Christian-Albrechts-University of Kiel; Neurological Centre
(C.L., B.H.), Hospital for Movement Disorders and Parkinson’s Disease, Bad Segeberg; Department of Performance, Neuroscience, Therapy and Health (B.H.), MSH–Medical School
Hamburg; Department of Neurodegeneration (D.B.), Hertie Institute for Clinical Brain Research, University of Tübingen, Germany.

Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

Copyright © 2020 American Academy of Neurology e2037

Copyright © 2020 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
 Glossary
BDI = Beck Depression Inventory; GP = general practitioner; MDS-UPDRS = Movement Disorder Society Unified
Parkinson’s Disease Rating Scale; MoCA = Montreal Cognitive Assessment; PD = Parkinson disease; PDQ-39 = Parkinson’s
Disease Questionnaire; RBD = REM sleep behavior disorder.
Recent years brought considerable progress towards early
detection in Parkinson disease (PD).1 The definition of the
prodromal phase presents a promising prospect to de-
celerate or even stop neurodegeneration at an early stage,
before motor symptoms occur.2 By identifying clinical
markers and biomarkers, the risk of an individual to be in the
prodromal phase can be calculated and many PD risk
cohorts have been built all over the world.3 These cohorts
are an important brick for research progress in this field and
the benefit, which may be derived from key findings, is be-
yond controversy. However, they are accompanied by ethi-
cal challenges, with obligations to the individuals within
these cohorts.
1. There is no reliable certainty that an individual is
definitely in the prodromal phase.4
2. Time to onset of the disease cannot be defined and may
range between months and decades.
3. There are no evident recommendations for individuals in
the prodromal phase, meaning that they are confronted
with an uncertain statement that they might develop PD
sometime in the future, without supportive consequences
for the individual at the time of disclosure.
This study therefore focuses on the perception of affected
individuals on risk disclosure in the face of missing therapy
options, and how important they rate the right not to know. In
a second step, we derive suggestions for the management/
handling of risk disclosure respecting the special ethical
challenges in the prodromal phase of PD.
Methods
Participants
A total of 121 patients with PD were recruited from the
outpatient and inpatient clinic of the Department of Neu-
rology at the University of Kiel. Inclusion criteria for
patients with PD were diagnosis of PD according to UK
brain bank criteria and ability to give written informed
consent and to understand the questionnaire. Twenty
patients participated in the preliminary feasibility study and
101 patients participated in the final (revised) questionnaire
study.
Standard protocol approvals, registrations,
and patient consents
The study was approved by the local ethical committee of the
Christian-Albrechts-University, Kiel. Written informed con-
sent was obtained from all participants.
e2038 Neurology | Volume 94, Number 19 | May 12, 2020
Copyright © 2020 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
Data availability
Data for interested researchers are available upon request.
Assessments
Questionnaire
In close interdisciplinary collaboration (neurology, ethics, and
neuropsychology), we designed a standardized questionnaire to
evaluate the patients’ perception on early diagnosis in PD. The
questionnaire was first tested in a preliminary feasibility study in
20 individuals. Afterwards, the questionnaire was adapted in terms
of better understanding. For the analysis presented here, only data
of the revised version of the questionnaire were used. See figure 1
for a detailed presentation of the 10 selected questions.
Clinical assessment
The Movement Disorder Society Unified Parkinson’s Disease
Rating Scale (MDS-UPDRS) was used to evaluate disease
severity. Cognition, mood, and quality of life were rated using
the Montreal Cognitive Assessment (MoCA), the Beck De-
pression Inventory (BDI), and the Parkinson’s Disease
Questionnaire (PDQ-39).
Statistics
Statistics were performed with SPSS 24.0 (SPSS Inc., Chi-
cago, IL). Distribution of all variables was tested using the
Kolmogorov-Smirnoff test. Afterwards, normally distributed
variables were compared using the Student t test and non-
normally distributed variables were compared using the
Mann-Whitney U test for 2-group comparison and the
Kruskal-Wallis test for 3-group comparison. Multiple com-
parisons were Bonferroni corrected.
Results
Group characteristics
The final questionnaire was filled out by 101 patients with PD.
Median age was 69 years (37–88); 59.4% of the participants
were male. Median MDS-UPDRS part III was 27 (1–66).
Median MoCA score was 24 (16–30). Median disease dura-
tion was 6 years (1–24).
Early diagnosis of clinically manifest PD
Questions 1 and 2: time to diagnosis
Median reported duration between first recognized onset of
motor symptoms and diagnosis of PD was 1.0 years (0–6
years). Thirty-five percent of participants reported a con-
firmed diagnosis within 1 year, 34% between 1 and 2 years,
and 32% longer than 2 years.
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Figure 1 Questionnaire on early diagnosis and detection in Parkinson disease

Questions 3 and 4: medical consultations
A median of 3 (1–20) medical consultations was indicated until
the diagnosis was confirmed. Sixteen percent needed more than
6 doctor visits to obtain the diagnosis; 6% needed more than 10
visits. The tentative diagnosis of PD was most frequently made
by general practitioners (GPs) (53.0%), followed by neurologists
(39.0%). Other disciplines mentioned included orthopedists,
psychiatrists, and therapists (e.g., physiotherapists).
36% of this group were treated according to misdiagnoses. Mis-
diagnoses included mostly other neurologic diagnoses (e.g., es-
sential tremor, multiple sclerosis, polyneuropathy), psychiatric/
psychological diagnoses (e.g., burnout, depression, stress), or or-
thopedic (e.g., arthrosis) or internal diseases (e.g., cancer, thyroid
disease). Insufficient treatments included in particular psycho-
logical measures (e.g., antidepressants, psychological therapy) and
nonpharmacologic interventions (e.g., osteopathy, acupuncture).

Question 5: false diagnoses Question 6: psychological strain

Thirty-three percent of the participants claimed that before the Sixty-two percent of the participants declared that the time
diagnosis of PD was mentioned, other diagnoses were made, and from onset of motor symptoms to diagnosis was burdensome.

Neurology.org/N Neurology | Volume 94, Number 19 | May 12, 2020 e2039

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 Figure 2 Knowing the risk
Of these, 29.7% remembered this time as maximally bur-
densome when asked to rate the strain on a Likert
scale (1–10).
Evaluation of early diagnosis in PD
Question 7, a and b: knowing the risk
Fewer than half of the patients (46%) indicated that they
would have liked to know about their risk for PD, even if there
would have been no medical treatment to postpone the onset
of the disease. However, 85% indicated that they would have
liked to know of their risk for PD if they would have received
instructions on how lifestyle changes may alter the course of
the disease (figure 2).
Question 8: change of lifestyle
Thirty-nine percent declared that they would have changed
something in their life if they would have known about their
risk for PD. The most frequently listed changes were stress
reduction (less workload, more enjoyment of life and travel-
ing) and changes in lifestyle (healthy eating and exercise).
Attitudes towards risk disclosure and possible
support for individuals at risk
Question 9: information on personal risk
Ten percent of the participants believed that it would not be
right to inform individuals about their risk for PD, while 23%
said the information should be given. Sixty-seven percent
declared that they would agree with risk disclosure under
specific conditions: 18% voted for a risk disclosure if it would
lead to new insights for other patients, 37% agreed if it would
lead to new therapy options for the affected individual, and
87% agreed with a risk disclosure if it had been ascertained
beforehand that the affected individual wanted to know his or
her risk (figure 3).
Question 10: help for people at risk
Fifty-four percent of the participants endorsed discussion of
the results with the family doctor or neurologist, followed by
49% who wished to have access to a contact person at
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PD = Parkinson disease.
a medical center for regular follow-up. Forty-nine percent
considered advice on lifestyle and 43% information material
as helpful. Thirty-six percent voted for an appointment with
relatives/partners, 36% for a special sports portfolio, and 35%
for the arrangement of a near-term second appointment.
Twenty-five percent endorsed an appointment with a psy-
chologist and 17% supported the idea of providing contacts
from patient support groups.
Influence of clinical factors on answers
To evaluate whether specific epidemiologic or clinical char-
acteristics may influence the answers of patients with PD on
the questions concerning early risk disclosure, individuals
voting yes on questions 7 and 8 were compared to individuals
voting no (or “yes, but only if” in question 9).
When comparing age, sex, disease duration, MDS-UPDRS
part I–IV, BDI, MoCA, and PDQ-39, no differences were seen
for question 7, a and b (knowing the risk) and question 9
(information on personal risk). However, when comparing
the groups with different answers for question 8 (change of
lifestyle), individuals indicating that they would have changed
something in their life if they knew that they had a higher risk
for developing PD were found to be younger than individuals
indicating they would not have changed anything (yes: 63
years [43–80] vs no: 71 years [37–88], p = 0.002).
Discussion
Recent years brought a considerable moral dilemma in PD
research: the development of disease course–modifying ther-
apeutic strategies is highly dependent on work with prodromal
patient cohorts and therefore has a clear societal benefit, but the
recruitment of these cohorts is carried out with a debatable
individual risk–benefit ratio for the participants.
This study focused on ethical implications related to early
detection in PD by asking affected individuals about their
perception on the issue of risk disclosure. The study reveals
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Figure 3 Information on personal risk
that, although the time from first motor symptoms to final
diagnosis of PD is burdensome for most patients with PD, the
majority of them are skeptical about early risk disclosure and
rate the personal right not to know as highly important.
However, their answers lead to possible strategies to over-
come this ethical dilemma.
When looking at the time to diagnosis, the number of con-
sultations necessary, the number of misdiagnoses, and in-
sufficient or sometimes incorrect treatments, it becomes
evident that correct and early diagnosis of the clinical phase of
PD is an issue, as mentioned earlier.5 About one third of the
patients evaluated the phase from first recognized motor
symptoms to the final diagnosis as very burdensome, and
another third of them as burdensome. Efforts have been made
to improve diagnosis of PD, including new diagnostic criteria
for PD,6,7 but it appears that PD is often not the first diagnosis
considered. A better understanding of markers of the pro-
dromal phase may alleviate the burden of long uncertainty and
misdiagnoses in the clinical phase. As an example, the sus-
pected diagnosis of PD is more obvious if an individual has
been followed up for REM sleep behavior disorder (RBD),
and this might lead to earlier initiation of the required di-
agnostic steps once the patient develops motor symptoms.
However, it will be particularly important that the currently
known most specific prodromal markers are known not only
by specialized researchers but also by GPs.
Neurology.org/N
Copyright © 2020 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
PD = Parkinson disease.
Our results show that patients with PD evaluated risk dis-
closure for PD critically. More than half of the patients (54%)
remarked that they would not have liked to know about their
risk if there would have been no medical treatment. This is
particularly noteworthy, as there is no medical treatment to
offer to individuals at risk. Eleven percent of patients indicated
that they would not support a risk disclosure to individuals at
risk for PD under any circumstances. This perception of early
detection was not influenced by clinical factors such as se-
verity of the disease, depression, cognition, or age. Moreover,
one often cited reason to justify risk disclosure is the possi-
bility of individuals to recapitulate life plans and choices.
However, in our study, only 39% stated that they would have
changed something in their life.
Taken together, these results indicate that the active re-
cruitment of individuals for prodromal/at risk cohorts and the
related revealing of personal risk factors for PD results in
conflicting interests in a considerable number of individuals.
Our results are comparable with a previously performed study
in relatives of patients with PD, of whom only 60% reported
interest in early detection of the disease in the absence of
treatment options.8
Ethical issues of early detection in neurodegeneration have
already been addressed in other neurodegenerative diseases,
in particular in Alzheimer disease and Huntington disease,
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 where genetic testing can provide information on the in-
dividual risk for developing a disease.9–14 One important
difference regarding the clinical markers of PD is that in these
diseases biomarker and particularly genetic testing is carried
out after obtaining informed consent. Individuals can be in-
formed about the pros and cons of risk disclosure and can
then decide whether they want to know as well as the time and
extent of risk disclosure. Recruitment of individuals with
potential clinical prodromal PD signs needs active call-ups
using, for example, newspapers or postings.15 Individuals’
attention is actively drawn to the fact that specific symptoms
they may have such as hyposmia, constipation, or RBD might
be a sign of early PD. The process of risk disclosure has
therefore already started before the possible participant con-
tacts the research team; it is accordingly not possible to ensure
an autonomous decision for the right not to know.
The ethical considerations in this context gain further signif-
icance when looking at previous studies, which showed that
even when patients consented to an assessment of their in-
dividual risk of neurodegenerative diseases, this information
could trigger anxiety, depression, or suicidal behavior.16–18
Therefore, we take the answers of our patients regarding
options that may facilitate risk disclosure seriously and suggest
them to be considered in further research.
1. Change of lifestyle: One key issue is the fact that the
number of patients with PD who would have liked to
know about their risk for PD increased considerably,
from 46% to 85%, when indicating that they could have
positively influenced the disease course by changing their
lifestyle. This finding is also reflected in the question
about what individuals would have changed if they had
known of their risk. The most frequent answers of
patients with PD were that they would have changed
their lifestyle, including stress management, workload,
physical activity, and nutrition. Moreover, 49% rated
advice/guidance on lifestyle as particularly helpful after
risk disclosure. It therefore seems crucial to consider the
effect of changes in lifestyle on the progression of
neurodegeneration. In fact, there is considerable evi-
dence that regular physical activity can be disease-
modifying in PD. A large number of trials in the mouse
models of PD (e.g., the 6-OHDA and MPTP model)
have shown that exercise can modulate neuroinflamma-
tion and the release of neutrophic factors.19,20 Moreover,
there is increasing evidence for disease-modifying effects
of several nutrients and diets. Along with others,
especially polyphenols (derived from olive oil, berries,
or tea) and omega-3-polyunsatured oils (derived from
fish) have been demonstrated to modulate oxidative
stress and neuroinflammation, to increase neurorestora-
tion and intracerebral cell membrane integrity, and to
possibly even influence α-synuclein aggregation.21,22
Taken together, the current state of relevant studies
indicates that physical activity and specific nutritional
e2042 Neurology | Volume 94, Number 19 | May 12, 2020
Copyright © 2020 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
habits might act as a form of disease-modifying treatment
for patients with PD already in the prodromal phase. The
importance of lifestyle interventions for at risk cohorts
has been long recognized in other diseases.23–25 An
important example for the success of lifestyle interven-
tions in neurodegeneration is the FINGER study, which
showed that a multimodal lifestyle intervention could
counteract cognitive decline in an at risk cohort.26
Although we do not have progression or specific
outcome markers for prodromal PD, this and similar
studies should be considered as central aspects in the
communication with individuals at risk to reinforce
positive changes of lifestyle and strengthen patient
empowerment. Of course, it can be argued that
changes in lifestyle should always be emphasized in
the general population, independently from a personal
risk for neurodegenerative diseases, as exercise and
changes in diet are important preventive factors for
many other diseases. However, the positive response
and high recruitment rates for many interventional
lifestyle studies indicate that the knowledge of an
individual at high risk for a specific disease might be
a key driver to change lifestyle habits, although the
importance of a healthy lifestyle in general has been
known before. Ideally, risk disclosure should be
combined with individual advice on how lifestyle
changes can be implemented and what particular
aspects of a healthy lifestyle can be considered.
2. Establishment of an early diagnosis culture and trans-
parency: The majority of patients with PD in this study
indicated that they would endorse an early risk disclosure
if it would have been ascertained before that the affected
individual wants to know the risk. As mentioned, this is
easier to do for, for example, genetic testing, but how
could this be implemented for already manifest clinical
signs? Our study shows that in the German health system
GPs play a crucial role in making the first tentative
diagnosis and leading the way for further diagnostics and
treatment. One possible scenario might be that GPs
routinely assess in the setting of preventative check-ups the
individual’s wish for information on early risk detection for
untreatable diseases. This will also enable the crucial need
for transparency: informed consent should include in-
formation on the important risks of participating in this
research, in particular the uncertainty that goes along with
early risk disclosure. Although laborious to implement, this
might be a possible solution for the identification of at risk
individuals for different diseases and an important step to
better patient involvement.
3. Support: The majority of participants of this study rated
good patient care from medical specialists and regular
follow-ups as an important measure after risk disclosure.
This principle should be taken into account when
building risk cohorts, which include in most cases regular
follow-ups over many years and therefore might be an
ideal basis for regular, long-term support.
Neurology.org/N
4. Autonomy: The individual’s right to decide if he or she
wants to know or not to know is of highest priority, but is
limited in our currently used active recruitment
strategies. Therefore, an important objective of future
studies should be to implement as many steps as possible
to enable autonomous decision-making for risk
disclosure.
Several limitations of the study have to be addressed. First,
this study focused on already affected individuals and relies on
their memory and perception of the time before diagnosis in
a retrospective way. Moreover, it is evident that a question-
naire in about 100 patients cannot provide a standard of care.
We did not specifically exclude individuals with cognitive
impairment, and it can be discussed whether this might have
affected the answers to the questions. However, we did not see
any differences in the answers between individuals with high
and low MoCA scores, indicating that this issue is not of high
relevance for the results.
speaker’s honoraria from UCB Pharma GmbH, TEVA Pharma
GmbH, AbbVie GmbH, BIAL, and Zambon. D. Berg reports
grants from Janssen Pharmaceuticals, the Damp Foundation, the
German Parkinson’s Disease Association (dPV), BMWi, BMBF,
and the ParkinsonFonds Deutschland GmbH; grants, speaker’s
honoraria, and consultancy honoraria from UCB Pharma GmbH
and Lundbeck; grants and speaker’s honoraria from TEVA
Pharma GmbH; grants and consultancies from Novartis Pharma
GmbH; speaker’s honoraria and consultancy honoraria from
BIAL and Biogen; and honoraria from Bayer and Zambon outside
the submitted work. Go to Neurology.org/N for full disclosures.
Publication history
Received by Neurology August 23, 2019. Accepted in final form
November 19, 2019.
Appendix Authors
Name Location Contribution

It is beyond doubt that the recruitment and investigation of at- Eva Department of Conception, organization,
risk cohorts is of great importance to prepare the way for Schaeffer, Neurology, Christian- and execution of the study;
MD Albrechts-University of design and execution of the
a better understanding and potentially disease-course- Kiel statistical analysis; writing
modifying therapies in PD.27 Compared to other diseases, it of the first draft of the
manuscript
is notable that studies dealing with the ethical issues of early
detection in PD are currently underrepresented and mainly Annette Institute of Experimental Conception, organization,
Rogge, MD Medicine, Medical Ethics, and execution of the study;
focus on genetics,28–30 although the calculated risk, for ex- Christian-Albrechts- review and critique of the
ample in patients with RBD, is considerably higher than, for University of Kiel statistical analysis; review
example, risk determination of APOE testing.31 and critique of the
manuscript

Katharina Department of Conception, organization,

The ethical dilemma arising with early detection in PD has to Nieding Neurology, Christian- and execution of the study;
be faced and discussed,32 in particular with regard to active Albrechts-University of execution of the statistical
recruitment strategies. Results of this retrospective survey Kiel analysis; review of the
manuscript
show that this is a relevant aspect for our patients and not only
a philosophical construct. Communication of uncertainty and Vera Department of Execution of the study,
Helmker Neurology, Christian- review of the manuscript
respecting the individual’s right not to know33–35 are major Albrechts-University of
challenges and yet an important basis for patient involvement Kiel

and empowerment. Furthermore, we could derive from the Christa Hospital for Movement Execution of the study,
patient’s answers different proposals to optimize risk disclo- Letsch Disorders and Parkinson’s review of the manuscript
Disease, Neurologic
sure that may be approached. Efforts should be made to fur- Centre, Bad Segeberg
ther elucidate ethical implications of early detection in
Björn Hospital for Movement Execution of the study,
neurodegeneration, including the perception and opinion of Hauptmann, Disorders and Parkinson’s review of the manuscript
the general population and individuals at risk, in particular MD Disease, Neurologic
Centre, Bad Segeberg
individuals with RBD.
Daniela Berg, Department of Conception, design, and
Acknowledgment MD Neurology, Christian- organization of the study;
Albrechts-University of review and critique of the
The authors thank the patients for their commitment. Kiel statistical analysis; review
and critique of the
manuscript
Study funding
No targeted funding reported.

Disclosure
E. Schaeffer received intramural research funding from the Uni-
versity of Kiel and speaker’s honoraria from Bayer Vital GmbH
and Novartis, outside the submitted work. A. Rogge, K. Nieding,
Vera Helmker, and C. Letsch report no relevant disclosures. B.
Hauptmann reports grants from Innovationsfond/GBA and
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