(1) The document summarizes the results of a survey conducted at the 2017 Alzheimer's Association International Conference to gather insights on Alzheimer's disease research. (2) Over half of respondents believed the foremost challenge in neuroscience drug development is target identification. (3) The amyloid hypothesis was seen as the most promising research area, though tau protein and inflammation were also viewed as important. (4) Pre-screening subjects in the community was believed to have the biggest positive impact on recruiting prodromal Alzheimer's patients.

1. Alzheimer’s Disease Research
Insight Report 2017
Page 01 of 9PRA Health Sciences, Inc. ©2017
JULY 2017
PRA INSIGHTS REPORT
Alzheimer’s Disease Research

2. Page 1 of 9PRA Health Sciences, Inc. ©2017
Alzheimer’s Disease Research
Insight Report 2017
TABLE OF CONTENTS
Introduction
Methodology
Summary
Question One: Demographics
Question Two: The Foremost Challenge in Neuroscience Drug Development
Question Three: Promising Threads in Alzheimer’s Research
Question Four: Recruitment of Prodromal Subjects
Question Five: Barriers Toward Participation in Alzheimer’s Disease Trials
Question Six: The Future of Alzheimer’s Disease Research
External Sources
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Insight Report 2017
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INTRODUCTION
The Alzheimer’s Association International Conference (AAIC) is the world’s largest forum for
dementia research, attended by approximately 5,600 individuals from industry, academia,
non-profit organizations and government bodies.
Following the success of the PRA Insights survey which took place at DIA US, PRA’s Neuroscience
and Pain team piloted the scheme in Europe with a short, primarily multi-choice questionnaire,
run across all four exhibition days to gather insight on clinical development and the future of
research in Alzheimer’s disease.
The questions were as follows:
1. What do you believe is the foremost challenge in neuroscience drug development?
• Target identification/validation
• Regulatory review and approval
• Uncertainty/risk
• Funding
2. What do you believe is the most promising thread of Alzheimer’s research?
• Amyloid hypothesis
• Tau protein
• Beta-secretase (BACE)
• Hormonal research
• Inflammation
• 5HT6 receptor
3. What do you believe could impact recruitment of prodromal Alzheimer’s patients in a
positive way?
• Interacting with online patient communities
• Digital screening of potential subjects with self-reported cognitive symptoms
• Pre-screening in the community
• Streamlining site visits combined with virtual reporting tools
• 60/40 alternate allocation ratio towards active treatment
4. What do you feel are the main barriers toward participation in Alzheimer’s
trials? (pick the 3 most important)
• Low trial awareness
• Comorbidities
• Concomitant medications
• Risks of side effects
• Barriers associated with procedures (eg. unwillingness to undergo procedures
such as lumbar puncture)
• Risk of placebo
• Travel and other logistics
• Informed consent

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Insight Report 2017
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METHODOLOGY
Data for this report was gathered during exhibit hours at the Alzheimer’s Association International
Conference (AAIC) over 16-19 July, 2017. PRA ran a single survey over the four exhibition days,
obtaining a total of 119 responses.
Participants self-selected their company affiliation from four choices:
• CRO
• Investigator/Site
• Pharmaceutical/Biotechnology company
• Service/product provider
Of the 119 responses, the majority (57%) identified as coming from an “Investigator/site”
background, followed by 24% from pharma/biotech, 10% for Service/product provider to
the industry and 9% from a CRO. This largely reflected the attendance of the conference itself.
5. Do you believe that a Disease Modifying Drug for Alzheimer’s will have been discovered by
target 2025?
• Yes
• No
SUMMARY
QUESTION ONE: WHICH CATEGORY BEST DESCRIBES YOU?
(N=119)
AAIC 2017
(N = 119)
CRO | 11%
Pharma/Biotech
Company | 29%
Service/Product
Provider | 12%
Investigator/Site | 67%
Question 1

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Insight Report 2017
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QUESTION TWO: WHAT DO YOU BELIEVE IS THE FOREMOST CHALLENGE IN
NEUROSCIENCE DRUG DEVELOPMENT? (N=118, 1 PERSON SKIPPED)
This question was selected to address the fact that despite major advances in science and
our understanding of the brain, research has not yet translated into meaningful therapeutic
discoveries for patients suffering from a broad range of brain disorders, including Alzheimer’s
disease. We sought to understand the following:
• Whether our peers felt target identification and validation is lagging in comparison to
other therapeutic areas such as metabolic disorders, infectious disease, and oncology.
• Is the lack of clear regulatory pathways off-putting?
• Are recent failures in research causing uncertainty, has a prior failure truly tested a
hypothesis?
• Funding – is there a lack of financial backing for neuroscience research in general?
AAIC 2017
N = 118
1 PERSON SKIPPED
Funding | 17%
Target identification/
validation | 70%
Regulatory review and
approval | 12%
Uncertainty/risk | 19%
Question 2
More than half of respondents were of the opinion that target identification was the foremost
hurdle. Drug target identification is one of the most costly, labor-intensive and complex areas
of drug development. The current main targets for Alzheimer’s disease are amyloid, followed by
inflammation and tau. However, improved understanding of the onset and progression of
Alzheimer’s disease will result in more efficient therapeutic approaches and expand potential
targets. This opinion was mirrored in each respondent company grouping, most decisively within
the Investigator/site sector (70%), followed by Pharma/biotech (64%).

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QUESTION THREE: WHAT DO YOU BELIEVE IS THE MOST PROMISING THREAD OF
ALZHEIMER’S RESEARCH? (N=117, 2 SKIPPED)
As a natural follow-on from question one, we asked our survey respondents to identify the
strand of Alzheimer’s disease research that they felt was most encouraging. Below follows a
short explanation of the theories explored and an overview of their basic premise:
• Amyloid hypothesis - a microscopic protein fragment called beta-amyloid can
accumulate in the brain, disrupting communication between brain cells and eventually
killing them. Some researchers believe that flaws in the processes governing production,
accumulation or disposal of beta-amyloid are the primary cause of Alzheimer’s disease.
• Tau protein - abnormal aggregation of tau protein in the brain leads to the formation of
tangles within nerve cells. In healthy areas, tau helps keep the transport system on track.
But in areas where tangles are forming, the twisted strands of tau essentially disintegrate
the transport system so that nutrients and other essential supplies can no longer move
through the cells, which eventually die.
• Beta-secretase (BACE) – closely related to the amyloid hypothesis, research into BACE
inhibitors is currently ongoing, which, in theory would prevent build-up of beta-amyloid
from forming.
• Hormonal research - changes in estrogen levels (for women and men) during aging
may increase risk for Alzheimer’s disease, use of selective estrogen receptor modulators
(SERMs) to improve cognition, and studies of genetic risk factors could hold promise.
• Inflammation – a mitochondrial protein, TSPO, accumulates in the inflamed brain under
conditions that activate microglia. Along with amyloid, this protein is increased in the
brains of people with Alzheimer’s disease.
• 5-HT6 receptor – the 5-HT6 receptor is a subtype of 5-HT receptor that binds serotonin.
5-HT6 antagonists improve cognition, learning, and memory, agents such as idalopirdine
and intepirdine are being developed as novel treatments for Alzheimer’s disease and
other forms of dementia.
Feedback received from survey participants was to consider lifestyle factors as an addition to this
category. On the final day of the AAIC conference The Lancet presented data which suggested
one in three cases of dementia could be prevented by addressing nine lifestyle factors, including
increase in education, physical activity and social contact.

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Insight Report 2017
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Hormonal research | 5%
5HT6 | 6%
Amyloid hypothesis | 43%
Inflammation | 27%
Tau protein | 31%
Beta-secretase (BASE) | 5%
AAIC 2017
N = 117
2 PEOPLE SKIPPED
Question 3
Respondents were largely still confident in the amyloid hypothesis, within each company
grouping the amyloid hypothesis garnered 35%-45% of the vote. Despite failures for amyloid-
targeting compounds over the last year, some experts believe that the solution is to target
the disease earlier, focusing on mild-moderate patients or prodromal subjects.
QUESTION FOUR: WHAT DO YOU BELIEVE COULD IMPACT RECRUITMENT OF
PRODROMAL ALZHEIMER’S SUBJECTS IN A POSITIVE WAY?
(N=117, 2 SKIPPED)
Having identified that the amyloid hypothesis is still a very valid line of research and that the
key to a cure or disease modifying treatment could stem from targeting patients at the earliest
possible stage, recruitment of early onset and prodromal subjects has never been so important.
The Alzheimer’s Association recently identified that as many as 50,000 patients are required to
support current research. Patients with Mild Cognitive Impairment (MCI) or prodromal subjects
are often difficult to recruit, in part, due to biomarker eligibility requirements which may include
PET imaging and/or cerebrospinal fluid assessments. Screening of subjects is therefore costly
and time-consuming, with a significant screen fail rate. We wanted to find out what our peers felt
could help increase prodromal subject recruitment and offered the following options:
• Interacting with online patient communities
• Digital screening of potential subjects with self-reported cognitive symptoms
• Pre-screening in the community
• Streamlining site visits combined with virtual reporting tools
• 60/40 alternate allocation ratio towards active treatment

8. Alzheimer’s Disease Research
Insight Report 2017
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Question 4
AAIC 2017
N = 117
2 PEOPLE SKIPPED
Interacting with online
patient communications | 24%
Digital screeening of potential
subjects with self-reported
cognitive symptoms | 17%
Streamlining site visits
combined with virtual
reporting tools | 11%
Pre-screening in the
community | 59%
60/40 alternate allocaion
ratio towards active
treatment | 6%
Across all company types, pre-screening in the community was the most popular response. This
would perhaps entail recruiting subjects via advertisements for people with memory problems
or even depression. Several respondents also commented whilst at our booth that combining
pre-screening in the community with materials on the positive societal impact of research
participation could also be helpful.
QUESTION FIVE: WHAT DO YOU FEEL ARE THE MAIN BARRIERS TOWARD
PARTICIPATION IN ALZHEIMER’S TRIALS? (PICK THE 3 MOST IMPORTANT)
(N=117, 2 SKIPPED)
To mobilize subjects to take part in clinical trials it is very important for researchers to understand
the barriers preventing people from participation in Alzheimer’s disease studies.
We identified the following as factors which may obstruct a person from considering taking part
in clinical research:
• Low trial awareness
• Comorbidities
• Concomitant medications
• Risks of side effects
• Barriers associated with procedures (eg. unwillingness to undergo procedures such as
lumbar puncture)
• Risk of placebo

9. Alzheimer’s Disease Research
Insight Report 2017
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Question 5
Comorbidities | 25%
Travel and other
logistics | 27%
Risk of placebo | 16%
Informed consent | 5%
Low trial
awareness | 41%
Concomitant
medications | 25%
AAIC 2017
N = 117
2 PEOPLE SKIPPED
Barriers associated with
procedures (unwillingness
to undergo procedures
such as lumbar
puncture | 38%
Risk of side effects | 30%
Overall, we saw that low trial awareness was the most popular response, however, we did not see
the same unanimity among respondent groups as with other questions posed.
Whilst the Investigator/site and Pharma/biotech groups agreed that low trial awareness was the
key obstructive factor to research participation. The smaller CRO and Service/product provider to
the industry groups were not as certain. Whilst identifying low trial awareness as a primary factor,
they also identified barriers associated with procedures and travel/logistics as equally important.
Within the CRO group barriers associated with procedures was identified as the main factor
preventing potential volunteers participating in clinical trials.
• Travel and other logistics
• Informed consent
We allowed survey participants to select up to three answers and therefore have recorded the
answers to this question by instances of response.

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Insight Report 2017
Page 9 of 9PRA Health Sciences, Inc. ©2017
QUESTION SIX: DO YOU BELIEVE THAT A DISEASE MODIFYING DRUG FOR
ALZHEIMER’S WILL HAVE BEEN DISCOVERED BY TARGET 2025?
(N=116, 3 SKIPPED)
G7 leaders have pledged to find a cure or disease-modifying treatment for Alzheimer’s disease by
2025. We decided to end our survey with a general question on whether our survey respondents
felt that this was achievable.
71% of all respondents were hopeful that this was the case, in all respondent groups the majority
leaned toward an optimistic response.
Question 6
Yes
No
0% 40%10% 20% 30% 60%50% 70% 80%
71%
29%
N = 116 (3 skipped)
EXTERNAL SOURCES:
Alzheimer’s Research UK
Alzheimer’s Association
Brightfocus Foundation