Policy View

Research priorities to reduce the global burden of dementia

by 2025
Hiral Shah*, Emiliano Albanese*, Cynthia Duggan, Igor Rudan, Kenneth M Langa, Maria C Carrillo, Kit Yee Chan, Yves Joanette, Martin Prince,
Martin Rossor, Shekhar Saxena, Heather M Snyder, Reisa Sperling, Mathew Varghese, Huali Wang, Marc Wortmann, Tarun Dua

At the First WHO Ministerial Conference on Global Action Against Dementia in March, 2015, 160 delegates, including Lancet Neurol 2016; 15: 1285–94
representatives from 80 WHO Member States and four UN agencies, agreed on a call for action to reduce the global See Comment page 1202
burden of dementia by fostering a collective effort to advance research. To drive this effort, we completed a globally *First coauthors, contributed
representative research prioritisation exercise using an adapted version of the Child Health and Nutrition Research equally
Initiative method. We elicited 863 research questions from 201 participants and consolidated these questions into Department of Neurology,
59 thematic research avenues, which were scored anonymously by 162 researchers and stakeholders from 39 countries Columbia University, New
York, NY, USA (H Shah MD);
according to five criteria. Six of the top ten research priorities were focused on prevention, identification, and Department of Psychiatry,
reduction of dementia risk, and on delivery and quality of care for people with dementia and their carers. Other University of Geneva, Geneva,
priorities related to diagnosis, biomarkers, treatment development, basic research into disease mechanisms, and Switzerland
public awareness and understanding of dementia. Research priorities identified by this systematic international (Prof E Albanese MD);
Department of Neurology,
process should be mapped onto the global dementia research landscape to identify crucial gaps and inform and Washington University School
motivate policy makers, funders, and researchers to support and conduct research to reduce the global burden of of Medicine, St Louis, MO, USA
dementia. Efforts are needed by all stakeholders, including WHO, WHO Member States, and civil society, to (C Duggan PhD); Centre for
continuously monitor research investments and progress, through international platforms such as a Global Dementia Global Health Research and
WHO Collaborating Centre for
Observatory. With established research priorities, an opportunity now exists to translate the call for action into a Population Health Research
global dementia action plan to reduce the global burden of dementia. and Training, The Usher
Institute, University of
Edinburgh, Edinburgh, UK
Introduction global health4 to chronic non-communicable diseases5 and
(I Rudan PhD, K Y Chan PhD);
Population ageing will lead to a dramatic increase in mental health.6 These initiatives have had great merit in Department of Internal
dementia prevalence across all world regions. By 2050, spurring research progress, because the identification of Medicine, VA Center for Clinical
more than 131·5 million people are expected to be research priorities is crucial to inform governments, Management Research,
Institute for Social Research,
affected.1 Dementia is already a heavy burden for those funding agencies, and the private sector about how to
Institute for Healthcare Policy
living with the disease, their families, and society. The prioritise investments systematically. A fully transparent, and Innovation, University of
burden and global annual costs of US$818 billion are systematic, rigorous, replicable, and fair prioritisation Michigan, Ann Arbor, MI, USA
expected to increase substantially in the next few process, that is globally representative and involves all (Prof K M Langa MD); Medical
and Scientific Relations
decades.1 relevant stakeholders, is needed to guide a coordinated
Division, Alzheimer’s
An unprecedented coordinated global response is international response to the existing complex and Association, Chicago, IL, USA
imperative to effectively address the burden and sizeable challenges in dementia research. The Child (M C Carrillo PhD,
challenges of dementia. The public health approach to Health and Nutrition Research Initiative (CHNRI) method H M Snyder PhD); Nossal
Institute for Global Health,
dementia called for by WHO in 2012 has rapidly gained was developed to respond to this need for methodological
Melbourne School of
widespread support among world leaders, researchers, rigour and has been successfully used as a tool to assist Population and Global Health,
and stakeholders.2 At the historic G8 Dementia Summit decision making and consensus development in child University of Melbourne,
held in London in December, 2013, the G8 countries health and nutrition,7 and subsequently in several other Melbourne, VIC, Australia
(K Y Chan); Institute of Aging,
launched a Global Action Against Dementia. The priority-setting exercises,8 including research into Canadian Institutes of Health
12 agreed specific commitments included the disability9 and global mental health.10 Research, QC, Canada
identification of strategic research priority areas and the Past research prioritisation exercises in the specialty of (Y Joanette PhD); World
development of a coordinated international research dementia have been insightful and have used various Dementia Council, London, UK
(Y Joanette); Centre for Global
action plan,3 and culminated in the First WHO approaches and methods, but they have not been done Mental Health, Health Service
Ministerial Conference on Global Action Against on a global scale. For example, in both the USA and and Population Research
Dementia in March, 2015, which brought together Europe, unmet needs and research priorities for Department, King’s College
stakeholders (ie, policy makers, patients’ representatives, neurodegenerative diseases or Alzheimer’s disease have London, London, UK
(Prof M Prince MD); Dementia
funders, and advocates) and experts from research, been identified by non-systematic consultations with Research Centre, Department
clinical practice, and non-governmental organisations. selected groups of experts,11–13 or with health and social of Neurodegeneration, UCL
Since resources and funding for research are scant care professionals and patients’ and carers’ Institute of Neurology,
despite increases in recent years, research priorities need representatives.14 London, UK (Prof M Rossor MD);
Department of Mental Health
to be set to guide policy makers and funding organisations In this Policy View, we report the research priorities and Substance Abuse, World
as they work to advance the dementia research agenda. In that need to be addressed in the next 10 years to Health Organization, Geneva,
the past decade, several efforts, including the Grand substantially reduce the global burden of dementia on Switzerland (S Saxena MD,
Challenges initiatives, have been made successfully to patients, their families, and society. These priorities were T Dua MD); Center for
Alzheimer Research and
identify research priorities in various specialties, from identified through an adapted CHNRI exercise done

www.thelancet.com/neurology Vol 15 November 2016 1285

 Policy View
Treatment, Brigham and
Women’s Hospital,
Massachusetts General
Hospital, Harvard Medical
School, Boston, MA, USA
(R Sperling MD); Department of
Psychiatry, National Institute
of Mental Health and Neuro
Sciences, Bangalore, India
(Prof M Varghese MD[Psych]);
Dementia Care and Research
Center, Peking University
Institute of Mental Health,
Beijing Municipal Key
Laboratory for Translational
Research on Diagnosis and
Treatment of Dementia,
National Clinical Research
Center for Mental Disorders,
Peking University Sixth
Hospital, Beijing, China
(H Wang MD); and Alzheimer’s
Disease International, London,
UK (M Wortmann Master of Law)
Correspondence to:
Dr Tarun Dua, Programme for
Neurological Diseases and
Neuroscience, Evidence,
Research and Action on Mental
and Brain Disorders, Department
of Mental Health and Substance
Abuse, World Health
Organization, CH-1211
Geneva 27, Switzerland
duat@who.int
For more on the Grand
Challenges initiatives see
http://grandchallenges.org/
For more on the US Alzheimer’s
Association see https://www.
alz.org/
For more on the JPND initiative
see http://www.
neurodegenerationresearch.eu/
For more on the Canadian
Consortium on
Neurodegeneration in Aging
see http://ccna-ccnv.ca/
See Online for appendix
For more on Interdem see
http://interdem.org/
For more on Alzheimer’s
Disease International see
https://www.alz.co.uk/
For more on the 10/66
Dementia Research Group see
https://www.alz.co.uk/1066/
1286
under the auspices of WHO in preparation for the First
WHO Ministerial Conference on Global Action Against
Dementia. In panel 1, we list the aims of this Policy View.
In panel 2, we describe the context, purpose, and remit of
the present CHNRI exercise adapted to the specialty of
dementia.
Current status of dementia research
Although no systematic analysis is available of global
data that details the full scope of ongoing dementia
research projects, research expenditures, and the
number of individuals with dementia or their carers
participating in research, many individual national and
international efforts have been made to map assets
devoted to dementia research. For example, the
International Alzheimer’s Disease Research Portfolio15
was launched in 2010 by the US National Institute on
Aging and the US Alzheimer’s Association to categorise
research supported by public and private organisations
both in the USA and internationally using the Common
Alzheimer’s Disease Research Ontology (CADRO).16
The EU Joint Programme for Neurodegenerative
Disease Research (JPND) aims to draw together
researchers, existing research evidence, and national
funding bodies to align national programmes by
identification of common goals and to establish a
framework for coordinated future investment. The
Canadian Consortium on Neurodegeneration in Aging
was established by the Canadian Institutes of Health
Research to bring together leading Canadian researchers
in neurodegenerative diseases to promote inter-
institutional and interdisciplinary collaborative work
across Canada and internationally. Furthermore, the
Organisation for Economic Co-operation and
Development (OECD) has done an analysis of
G7 dementia research funding and identified key
objectives of dementia policy for countries to consider.17
An additional example of efforts to map dementia
research is the UK National Institute for Health
Research (NIHR) analysis of dementia research
participation in G7 countries (unpublished). Similar to
previous research prioritisation exercises, most existing
research portfolio analyses have had little involvement
Panel 1: Aims of this Policy View
• To describe the adapted Child Health and Nutrition
Research Initiative method used to identify global
dementia research priorities for the next 10 years
• To present our results on the top research priorities across
research domains and discuss the limitations of our study
• To compare our findings with those of previous
priority-setting exercises for dementia research
• To suggest implications for and provide recommendations
to policy makers, funding agencies, and other stakeholders
for future research investments
of stakeholders, including policy makers, patients’
representatives, funders, and advocates.
Methods
Identification of dementia research priorities
WHO initiated a dementia research prioritisation exercise
and entrusted an advisory group of internationally
recognised experts and stakeholders in the specialty of
dementia to lead the development of the scope, methods,
and implementation of the exercise. The group was
balanced in terms of sex, technical expertise, and regional
representation, with inclusion of experts, advocates, and
patients’ representatives from low-income and middle-
income countries (LMICs; appendix pp 2). Income
category was designated according to World Bank criteria.
The advisory group considered available methods to set
research priorities, including stakeholder interviews,
expert consultation, and Delphi consensus methods, and
ultimately chose the widely used CHNRI method because
it could address all the aims of the exercise.18 Closely
working with its key methodologist (IR), the advisory
group adapted the CHNRI method—which has previously
focused on the elicitation of research questions and
scoring of those questions by researchers alone—to this
dementia priority-setting exercise, including the
involvement of stakeholders (ie, policy makers, patients’
representatives, funders, and advocates) in the scoring
step, because their viewpoints were felt to be crucial to
shaping the global dementia research agenda and
informing the exercise.
Figure 1 describes the key steps of the CHNRI method
adapted to dementia research prioritisation. Briefly, we
combined several structured and unstructured strategies
to identify experts in dementia, ensuring global
representation and the widest possible range of
disciplinary expertise and perspectives. We identified the
most productive dementia researchers worldwide in the
past 5 years using Web of Science (appendix pp 3). Other
stakeholders were identified through WHO, OECD,
Global Action Against Dementia, Interdem, International
Alzheimer’s Disease Research Funder Consortium,
G7 Dementia Summit legacy events, World Innovation
Summit for Health, advisory group networks, and other
experts using a snowballing technique. In an effort to
reach out as much as possible to LMICs, Chinese
academic and scientific databases were systematically
searched and suitable experts invited to participate, and
members from Alzheimer’s Disease International (the
global umbrella organisation of all national Alzheimer’s
disease associations) and the 10/66 Dementia Research
Group of clinicians, health and care workers, and
researchers from LMICs were actively involved, in both
elicitation and scoring of research questions. We
contacted the identified experts and stakeholders via
email to solicit three to five research questions, and
chased non-responders up to two times to increase
response rates.
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Three researchers (HS, EA, and CD) independently
categorised all questions received according to three
predefined domains and four themes. The predefined
domains were basic science research (ie, discovery
research that underpins investigations into the cause,
development, detection, and treatment of disease),
clinical–translational research (ie, patient-oriented work
done with living people), and implementation research
(ie, provision and delivery of health and social care
services). The four themes were prevention, diagnosis,
treatment, and care. The advisory group, convened in a
2-day workshop held in London in January, 2015,
consolidated the research questions, which were renamed
thematic research avenues to avoid confusion, and
identified overarching research domains through iterative
discussion while being mindful of consistency in the level
of granularity and specificity of the questions (figure 1).
Scoring of the final list of consolidated thematic
research avenues took place over 2 weeks using an
online platform and Microsoft Excel spreadsheets when
internet access was problematic. Scorers were asked to
answer “Yes” (score 1), “No” (0), or “Not sure/I do not
know” (0·5) to five queries that defined the five scoring
criteria devised for this priority exercise: (1) potential for
success (“To the best of your knowledge and experience,
would you say that the proposed research would likely
be successful in reaching the proposed endpoint within
the next decade?”); (2) effect on burden reduction (“If
successful, would you say that this research has a
potential to markedly reduce the burden of dementia on
patients, caregivers and the society as a whole?”);
(3) potential for conceptual breakthrough (“If successful,
would you say that this research is likely to result
in a paradigm shift [‘game changer’] that would
fundamentally change our thinking or approach to the
challenge of dementia?”); (4) potential for translation
(“If successful, would you say that the proposed research
would likely lead to practical application, implementation
of new knowledge and/or be deliverable at scale?”); and
(5) equity (“If successful, would you say that the
proposed research outcome is likely to benefit people
living with or at risk of dementia, their carers, and
societies as a whole in an equitable manner? Please
consider countries, cultures, ethnicities, socio-economic
status, gender, age, and any other relevant factors”).
Analysis of thematic research avenue scores
Consistent with previous CHNRI exercises,18 intermediate
scores were calculated for each thematic research avenue
as the sum of the scores (“Yes”=1, “No”=0, and “Not sure/I
do not know”=0·5) divided by the number of scorers,
separately for each of the five scoring criteria. This resulted
in five numbers (one for each of the five scoring criteria)
ranging from 0 (low) to 1 (high), which represent the
collective wisdom of the scorers that a given thematic
research avenue would fulfil a given scoring criterion. We
then computed the overall priority score by calculating the
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Policy View
Panel 2: Context, purpose, and remit of the dementia research prioritisation project
Motivation
Dementia is severely disabling and affects patients, carers, families, and society. The
estimated number of people living with dementia is expected to reach 131·5 million by
2050. The G8 Dementia Summit declaration called for development of a coordinated
international action plan for research to better understand and track the full societal burden
of dementia, and to identify a cure or effective disease-modifying treatment by 2025.
Long-term goal
To enhance dementia prevention and care to avoid or delay the clinical manifestations of
the disease, and to improve the quality of life and social wellbeing of those affected, to
prepare for and reduce the social and economic burden on families and nations globally.
Population of interest
Those with or at risk of dementia, their carers and families, the community in which they
live, health and social workers, and society in general, worldwide.
Timeframe
The timeframe of 10 years (2015–25) was chosen in accordance with the political will
expressed at the G8 Dementia Summit, and was applicable to all key dementia research
domains.
Research domains and themes
Three research domains: basic, clinical–translational, and implementation science. Four
research themes: dementia prevention, diagnosis, treatment, and care.
Audience
Governments, international funding agencies, research communities, society, and other
relevant stakeholders.
mean of the five intermediate scores without applying any
weights, and ranked the thematic research avenues
accordingly. Additionally, for each thematic research
avenue, we calculated the percentage of scorers choosing
the most common response between “Yes”, “No”, and
“Not sure/I do not know”. We then calculated the mean of
these percentages across the five criteria to obtain the
mean expert agreement, a measure of cohesiveness or
dispersion in the scorers’ opinion around the overall
priority score.
Role of the funding source
The UK Department of Health provided funding for the
study, but had no role in study design, data collection,
data analysis, data interpretation, or writing of the report.
TD had full access to all the data in the study and
had final responsibility for the decision to submit for
publication.
Results
We identified 2004 experts (672 researchers and
1332 stakeholders; appendix pp 3–4). We successfully
contacted 1386 (69%) experts, of whom 201 (15%)
submitted their research questions. Experts were from
33 countries (23 high-income countries [HICs] and
ten middle-income countries in the WHO regions of
Europe, southeast Asia, Africa, the west Pacific, and the
Americas), and they proposed 863 individual research
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questions, a mean of four questions each (appendix 162 scorers, including 82 (41%) of 201 who had also
pp 3, 15–37). The consolidation process led to 59 thematic previously provided questions for the exercise, took part
research avenues (appendix pp 6–12) that were grouped in the survey to score the 59 thematic research avenues.
across seven overarching research domains (figure 2). Scorers were from 39 countries (21 HICs and 18 LMICs);
142 (88%) were researchers or clinicians; 59 (36%) were
from the Americas, 60 (37%) were from Europe, 27 (17%)
CHNRI steps Activities and actors Relevant events
were from the western Pacific, 11 (7%) were from Africa,
G8 Dementia
three (2%) were from southeast Asia, and one (1%) was
Initiator of the dementia priority-setting process—G8 member
states (December, 2013) Summit (London, from the eastern Mediterranean; and 90 (56%) were
December, 2013) between 41 and 60 years of age. However, 18 (11%) of the
scorers also designated themselves as carers of someone
Definition of Establishment of a group of technical experts* (WHO dementia with dementia, 23 (14%) as policy makers, 15 (9%) as civil
scopes and research prioritisation working group, October, 2014) society representatives, and one (1%) self-identified as a
methods
person with dementia.
Definition of the context, Review of previous G7 legacy events
Overall research priority scores for the 59 thematic
purpose, and remit dementia priority-setting, (Japan, Canada, research avenues ranged from 0·81 to 0·49 (appendix
exercises, and methods and the USA, pp 9–12). The mean expert agreement revealed that
2014)
53–78% of scorers shared their views on the 59 proposed
Creation of the WHO dementia research prioritisation advisory
thematic research avenues (appendix pp 9–12). The top
group (November, 2014) three research avenues in each overarching research
domain are shown in table 1, ranked according to their
overall research priority score.
Adaptation of the CHNRI method with assistance from its
inventor (IR) The theme of dementia risk reduction was the most
prevalent among the thematic research avenues that
received the highest overall research priority scores,
spanning basic research (eg, “Understand the
Elicitation of 2004 researchers 1386 participants 863 questions
research and stakeholders successfully received from contributions of vascular conditions to neurodegenerative
questions identified contacted 201 participants diseases causing dementia”); epidemiological research
(first contact (1185 did not
failed in respond)
(into risk and protective factors); clinical trials or public
618 participants†) health research, or both (eg, the exploration of the efficacy
of evidence-based interventions for primary and secondary
prevention of dementia, which was identified as the
leading research priority overall); and translational
Consolidation of Consolidation of Identification Definition of five Experts’ and
research questions into of overarching scoring criteria stakeholders’ research (to establish the best strategies to translate
questions 59 research goals and scoring workshop knowledge of modifiable risk factors into brain health
avenues procedures (London,
January, 2015) promotion in different cultures and settings).
The top thematic research avenues on quality and
delivery of care emphasised that high priority should be
given to psychosocial research into models of care in the
Scoring of Identification of Scoring surveys 162 participants
consolidated 106 independent open over (82 who had
community and across the disease course, including late-
research avenues scorers 2 weeks for provided life and end-of-life care (table 1). Also highlighted were
307 participants questions and multifaceted interventions, including e-health and
(201 who 80 independent
provided scorers) scored mobile health technologies for people with dementia;
questions and the 59 research burden reduction; education, training, and support of
106 independent avenues
scorers)
formal and informal carers and the health and social
workforce; and targeting of behavioural and psychological
symptoms of dementia. In the domain of diagnosis,
highest priority was given to research that would promote
Computation of Computation of Ranking of Dissemination of WHO Ministerial
priority scores priority scores research priorities identified
a timely and accurate diagnosis of dementia in primary
Conference on
according to according to research Global Action care practices through the development and validation of
scoring criteria overall scores priorities Against Dementia genetic, biological, and clinical biomarkers, and the
(Geneva, March,
2015) longitudinal cognitive surveillance of healthy individuals
to detect the earliest changes that distinguish normal
ageing from premanifest neurodegenerative diseases
Figure 1: Steps of the adapted Child Health and Nutrition Research Initiative method and relevant political
and policy events that cause dementia (table 1). The top research priority in
CHNRI=Child Health and Nutrition Research Initiative. *Researchers, health and social workers, and other the domain of pharmacological and non-pharmacological
stakeholders. †Could not identify contact information. translational research was the diversification of

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therapeutic approaches, followed by methodological
improvement of clinical trials, including adaptive designs
and better outcome measures (table 1).
Overall scores varied substantially by scoring criteria.
For instance, when considering ranking by the burden
reduction criterion, scores were highest for the
overarching research domains of quality of care and
delivery of care, whereas for the criterion of potential for
conceptual breakthrough, the highest score was for the
domain of physiology and progression of normal ageing
and disease pathogenesis. For the equity criterion, the
highest scores were for the overarching domains of
public awareness and delivery of care (figure 3).
Furthermore, although the potential for success and the
potential for translation criteria were both scored highly
for most thematic research avenues, the potential for
conceptual breakthrough criterion was considered less
likely (priority score 0·56), particularly for the thematic
research avenues pertaining to quality of care (priority
score 0·35; figure 3).
The scorers rated the potential effect on burden
reduction as the most important (mean score 3·7 [SD 1·2]),
followed by potential for success (3·4 [1·3]), potential
for translation (3·0 [1·5]), potential for conceptual
breakthrough (2·8 [1·5]), and equity (2·1 [1·3]; p<0·0001).
Priority-setting exercises for dementia research:
strengths and limitations
WHO dementia research prioritisation project
To address the reduction of the burden of dementia
globally in the next 10 years, this Policy View presents
priority scores for the 59 thematic research avenues and
seven overarching research domains identified by the
WHO dementia research prioritisation project. On the
basis of potential for success, equity, burden reduction,
and translation, six of the top ten research priorities,
ranked by overall score, were focused on prevention,
identification, and reduction of dementia risk, and on
quality of care and delivery of care for people with
dementia and their carers (table 1). The extended list of
top 20 priorities includes seven questions related to
diagnosis and biomarkers and to treatment development
(appendix pp 13–14). Basic research into disease
mechanisms was judged to have the greatest potential
for conceptual breakthrough. The dementia experts and
stakeholders, including policy makers and funders, who
took part in this globally representative CHNRI exercise
concurred that most of these thematic research avenues
could be successfully answered by 2025.
The CHNRI method is transparent, systematic,
rigorous, replicable, democratic (ie, gives equal voices to
all those who take part in it), and has been validated and
widely used to set research priorities in several specialties
of global health.8 The main output of our modified
CHNRI exercise is a list of meaningful research questions
provided by a group of more than 200 experts and
stakeholders, organised by defined overarching research
www.thelancet.com/neurology Vol 15 November 2016
Policy View
9 (15%)
6 (10%) Prevention, indentification, and reduction of
risk (ie, genetic, lifestyle, or environmental)
8 (14%)
Diagnosis, biomarker development, and
disease monitoring
Pharmacological and non-pharmacological
4 (7%)
clinical–translational research
6 (10%)
Quality of care for people with dementia and
their carers
Delivery of care and services for people with
dementia and their carers
12 (20%) Physiology and progression of normal ageing
and disease pathogenesis
Public awareness and understanding
14 (24%)
Figure 2: Number (%) of thematic research avenues by overarching research domain
domains, and then ranked according to explicit priority
criteria by more than 160 experts and stakeholders. Our
CHNRI exercise included between two times and ten
times more people than did previous CHNRI exercises,7
and is, to our knowledge, the first time that research
experts and stakeholders from all world regions have
contributed and scored specific research questions in the
dementia specialty.11–14,19 Nevertheless, some limitations
are worth noting. The application of the CHNRI method
to the specialty of dementia needed some contextual
adaptations of the selection of experts and scorers,
classification and consolidation of questions, and scoring
processes. However, the CHNRI method was originally
conceived to be adaptive and has been similarly
customised previously.7–9,20,21 Our adaptations were
collectively discussed and agreed under the guidance of
the CHNRI key methodologist (IR).
Despite efforts to include several disciplines and
represent all geographical regions and resource levels,
respondents were predominantly clinicians and
researchers, and the southeast Asian, African, and eastern
Mediterranean regions were under-represented. Although
this low representation might reflect low dementia
research and advocacy efforts and potential barriers to
participation that exist in these settings, we acknowledge
that priorities are likely to vary by culture, region, and
resource level. In this exercise, we were not able to
capture and examine these differences, and culture-
specific and system-specific research is needed. Never-
theless, participants were from 39 countries and global
representation was substantially higher than in other
CHNRI exercises.7,9,22 A global view was not sought in
previous dementia research prioritisation efforts.11–14,19
Furthermore, Delphi consensus and expert consultation
methods might be biased by potential circularity because
of the restricted number of participants and their potential
influence on both selection and ranking of research
topics. The CHNRI method does not allow any single
person to have any appreciable influence on the outcome.
The large number of scorers compared with the number
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of research questions implies that each participant
contributed to the final results by less than 1% (ie, one of
201 at the elicitation step and one of 162 at the scoring
step). Additionally, we used a combination of non-
structured and structured strategies to identify dementia
experts, only a proportion of whom were researchers, and
the groups of those respondents who proposed the
research questions and who scored the thematic research
avenues did not coincide. Yet, because participants were
mainly clinicians and researchers, we cannot exclude the
possibility that their perspective might have influenced
our results. However, the mean expert agreement was
higher than 70% for most of the top 20 priorities.
Moreover, too broad an inclusiveness of non-experts (ie,
not research experts or clinicians), which is crucial at the
research topics elicitation step, might be counter-
productive at the scoring step in CHNRI exercises, and
might dilute the differences in priority scores across
research topics through regression towards the mean.22
Equity was judged to be the least important of the five
scoring criteria. Nevertheless, the general concern for
translation was substantial, because our results show

Overall score (mean

expert agreement)
Prevention, identification, and reduction of risk
Explore single and multi-domain approaches for primary and secondary prevention of dementias based on evidence on risk/protective factors and the relationship 0·81 (76%)
with other chronic diseases
Understand the influence and interactions of non-modifiable (eg, gender, genetics, age) and modifiable (eg, physical activity, diet, and cognitive stimulation) risk and 0·76 (70%)
protective factors for dementia in population-based samples
Determine the feasibility, optimal mode of administration, and effectiveness of interventions to address risk factors for dementia (including physical activity, 0·75 (69%)
cognitive activity, education, nutritional factors, and others)
Quality of care for people with dementia and their carers
Determine the most effective interventions for educating, training, and supporting formal and informal carer(s) of people with dementia 0·74 (76%)
Determine and ensure optimal use of psychological and pharmacological treatments for behavioural and psychological symptoms of dementia (BPSD) to maximise 0·73 (69%)
patients’ quality of life and caregiver burden reduction
Develop and evaluate policies, investments, and plans for increasing the capacity, knowledge, skills, and interest of the health and social care workforce in the field of 0·69 (71%)
dementia
Delivery of care and services for people with dementia and their carers
Evaluate the relative effectiveness and identify the optimal models of care and support for people with dementia and their carers in the community (eg, collaborative 0·75 (74%)
care, integrated health and social care, case management) across the disease course
Identify strategies to anticipate and deliver effective and cost-effective late-life and end-of-life care for people with dementia, including advance care planning 0·74 (74%)
Understand the role of assistive and technological devices, including e-health and mobile health technology strategies, for people with dementia and/or their carer(s) 0·71 (66%)
Diagnosis, biomarker development, and disease monitoring
Identify clinical practice and health system-based interventions that would promote a timely and accurate diagnosis of dementia in primary health-care practices 0·79 (78%)
Establish longitudinal cognitive surveillance of healthy individuals to detect earliest changes that distinguish premanifest neurodegenerative diseases causing 0·73 (65%)
dementia from normal ageing, and which may be used as endpoints in primary prevention clinical trials
Develop and validate biomarkers—including biological, genetic, behavioural, and cognitive markers—for neurodegenerative brain diseases causing dementia, to 0·71 (67%)
identify similarities and differences between diseases and dementia subtypes, and assess progression from premanifest (presymptomatic) to late-stage diseases
Pharmacological and non-pharmacological clinical–translational research
Diversify therapeutic approaches (eg, pharmacological and non-pharmacological interventions) for discovery and development in clinical trials for neurodegenerative 0·77 (70%)
and other brain diseases that cause dementia
Promote collaborations to explore more efficient trials, adaptive trials, and combination therapy for dementia 0·73 (64%)
Identify, validate, and apply better outcome measures for clinical trials of cognition, function, and other biomarkers for neurodegenerative diseases causing dementia 0·70 (64%)
Public awareness and understanding
Determine how knowledge of modifiable risk factors for dementia can be translated into effective brain health promotion and dementia prevention messages, and 0·77 (71%)
coupled with communication strategies to effect behavioural change in different cultures and countries
Determine the effectiveness and cost-effectiveness of dementia-friendly communities, and other population strategies that target stigma and discrimination, and 0·67 (63%)
promote inclusion and quality of life
Understand cultural differences in attitudes towards people with dementia to determine culturally appropriate ways to promote carer support and reduce stigma 0·66 (64%)
Physiology and progression of normal ageing and disease pathogenesis
Understand the contributions of vascular conditions to neurodegenerative diseases causing dementia 0·77 (70%)
Identify underlying mechanisms of resilience to neurodegenerative diseases causing dementia at all stages (such as cognitive reserve, protective genotypes, and 0·73 (66%)
neuroprotection)
Understand the role of inflammation and of the immune system in the initiation/onset and progression of neurodegenerative diseases that lead to dementia 0·68 (64%)*
Investigate biological processes of neurodegenerative diseases to understand their contributions to dementia to optimise individualised therapeutic strategies 0·68 (60%)*

*Joint third priority.

Table 1: Top three thematic research avenues for each of the seven overarching research domains

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that there was a widespread and serious concern among
the 162 scorers that many research avenues are unlikely
to benefit those with or at risk of dementia and their
families in an equitable manner.
Although the prevalence of dementia will increase
steeply in the coming decades because of population
ageing,1 epidemiological evidence suggests a potential
reduction in dementia incidence in recent years,23,24 and
the results of the FINGER trial25 suggest that multidomain
interventions could halt cognitive decline in at-risk older
adults. These findings might increase the general
optimism of the scientific community, expressed in 2011,
that the risk of dementia seems to be decreasing.26 This
optimism is somewhat echoed in our results, which
suggest a general confidence that the worldwide burden
of dementia can be substantially reduced in the next
10 years, particularly through improved prevention and
care. However, similarly to a widespread concern
expressed by all stakeholders at the time of the launch of
the US National Alzheimer’s Project Act in 2011,26 the
scorers seemed to have little hope that any of the
59 thematic research avenues can lead to a “significant
paradigm shift that would fundamentally change our
thinking or approach to the challenge of dementia”. This
finding suggests that the evidence in this CHNRI exercise
was deemed largely insufficient to support the ambition
to identify a cure for dementia, or disease-modifying
treatment, by 2025, which was one of the most
emphasised outcomes of the 2013 G8 Dementia Summit.
The stress put on finding a cure for Alzheimer’s disease
in the next 10 years should probably be de-emphasised,
and has already been criticised in a Lancet Editorial that
warned: “The quest for new drugs must not overshadow
improving today’s care and patients’ lives.”27
Indeed, we argue that our results suggest a pragmatic
optimism in this large group of dementia experts, which
calls for a transformative evolution of funding
mechanisms toward the implementation of a global
dementia research agenda that should encompass
increased investments along with improved capacity
building and development of international partnerships
to allow real-time sharing of knowledge on a global scale.
The research priorities identified will inform and assist
the balance of this research investment across research
domains.
Previous priority-setting exercises
Several consultations and initiatives that have been done
in recent years in HICs have produced research
recommendations for better detection,28 prevention,11 and
treatment29,30 of dementia, and to improve the quality of
life of people affected by dementia as well as their families
and carers (table 2).14 In these and other priority-setting
exercises that have been done in the USA12,26 and Europe,19
research themes were defined through a series of highly
structured workshops, and the recommendations for
research priorities, which were identified through
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Policy View
Prevention, indentification, and reduction of risk
Diagnosis, biomarker development, and disease monitoring
Pharmacological and non-pharmacological clinical–translational research
Quality of care for people with dementia and their carers
Delivery of care and services for people with dementia and their carers
Physiology and progression of normal ageing and disease pathogenesis
Public awareness and understanding
1·0
0·9
0·8
0·7
Main priority score
0·6
0·5
0·4
0·3
0·2
0·1
0
Potential for Effect on Potential for Potential for Equity
success burden conceptual translation
reduction breakthrough
Figure 3: Mean of the priority scores for the top 20 thematic research avenues for each of the seven
overarching research domains across the five scoring criteria
discussion but without formal scoring procedures,12,19 were For more on the US National
conceived to inform pre-existing plans and agendas (eg, Alzheimer’s Project Act see
http://napa.alz.org/
the US National Alzheimer’s Project Act26 and the EU
JPND research initiative19). Comparisons are not
straightforward because the scope and methods used
varied across these efforts. The research domains and
priorities identified in this CHNRI exercise have
commonalities with the broad themes,19 goals,12,26 and
recommendations13 previously reported, and are in broad
agreement with the top ten research priorities identified
in a recent James Lind Alliance exercise that encapsulated
“the views of people with dementia and their carers, and
health and social care practitioners”.14 However, the
CHNRI method is the soundest available in global health
to identify research priorities, and its output has the great
advantage of providing an intuitive list of meaningful
research questions. Compared with HICs, the prevalence
and burden of dementia are greater in LMICs, whereas
resources, research, and advocacy are scant;2 thus, in this
first instance of application of the CHNRI method to the
specialty of dementia, a global representation of the
articulated landscape of dementia researchers and
stakeholders was deemed crucial to achieve the goal of
identifying the top research priorities that have the
greatest potential to reduce the burden of dementia on a
global scale.
Policy implications
The 59 thematic research avenues and the seven
overarching research domains presented in this Policy
View cover comprehensively the action points of the WHO
call for action document that was adopted by more than
160 representatives, including 80 WHO Member States,
on March 17, 2015, at the First WHO Ministerial
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 Policy View

Goal
Leon Thal Symposia To establish a process for
(2008–09)11 creating a roadmap for policy
change to encourage
development of treatments to
prevent dementia
EU Joint Programme To address challenges of
for neurodegenerative disorders
Neurodegenerative and establish a framework for
Disease Research future research investments
(2012)19
Workgroup on the US To delineate a comprehensive Causative pathogenesis; early detection
National Alzheimer’s 10-year scientific agenda for and biomarkers; interventions; health
Project Act (2012)26 early detection and develop a service research (national: USA)
broad range of interventions for
AD and dementia
Ware Invitational To develop dementia research
Summit (2012)12 recommendations for the
scientific community, policy
makers, legislators, advocacy
groups, and clinicians
James Lind Alliance To identify funding allocation
and UK Alzheimer’s by identification of research
Society Dementia priorities and gaps in dementia
Priority Setting prevention, diagnosis,
Partnership (2013)14 treatment, and care, from the
perspectives of people with
dementia, carers, and health
and social care professionals
New York Academy To examine the challenges of
of Sciences AD and and explore solutions to
dementia research improve productivity of
roadmap (2014)13 biomedical research, and
accelerate development of new
diagnostics and therapeutics
WHO dementia To identify research priorities
research prioritisation that have the greatest potential
project (2015) to reduce the burden of
dementia on a global scale
Preset research domains (geographical Methods (participants)
region)
Process of drug discovery and
development, and clinical trials;
development of preventive treatments
for AD and dementia (national: USA)
The origins of neurodegenerative
diseases; disease mechanisms and
models; disease definitions and diagnosis;
development of treatments, preventive
strategies, and interventions; and health
care and social care (international: EU,
Switzerland, Canada, Norway, and Israel)
Biomarkers; clinical care and health
services research; drug development;
health economics, policy, and ethics
(national: USA, but included
international experts)
Prevention, diagnosis, treatment, and
care (national: UK)
Basic research; early development and
translational research; prevention trials;
and public–private interface (national:
USA)
Three predefined domains: basic,
clinical–translational, and
implementation science; four predefined
research themes: dementia prevention,
diagnosis, treatment, and care
(international)
Three think tank meetings with participants divided
into four groups; priorities decided by consensus
(70 international leaders in dementia research,
friends and colleagues of Leon Thal)
A scientific advisory board provided
recommendations based on a series of thematic
workshops and consultations (unspecified number of
research opinion leaders and stakeholders from
industry, patients’ representatives, health and social
care professionals, and carers)
The workgroup drafted a scientific agenda as a so-
called living document, incorporated feedback, and
shared it with an advisory council (unspecified
number of AD researchers across the USA)
Preliminary recommendations, based on the work of Four main goals and various
four workgroups, were discussed and integrated into related recommendations for their
a set of priorities, recommendations, and action plans implementation through research,
regulations, and funding
Questions (n=4000) elicited through a national
survey and consolidated into a list (n=146) that was
submitted to 36 partner organisations, which ranked
their top ten priorities through internal consultation;
the final top-ten list was agreed upon through
discussion and nominal group techniques
(1500 people completed the survey;
18 representatives from partner organisations
provided the final top-ten list)
Recommendations developed by consensus of
members of the Alzheimer’s Disease and Dementia
Leadership Council, composed of experts from
pharmaceutical and technical industry, academic
researchers, government representatives, and
advocacy groups
Adapted CHNRI method used to elicit research
questions (n=863) and consolidate, score, and rank
research priorities (n=59; 281 experts in dementia,
including researchers, policy makers, funders, and
patient advocates, provided research questions or
scored thematic research avenues)
Main output format
Wide-ranging, agency-specific,
scientific, and public policy
recommendations, with a focus on
development of treatments to
delay or prevent onset of disabling
symptoms of AD
Nine enabling activities (from
research capability and
infrastructures, public–private
partnerships, to education and
training) across five preset
thematic research priorities
An articulated scientific agenda,
with a focus on early detection and
interventions to prevent dementia
or maintain independence in those
affected, encompassing scientific
and infrastructural challenges, and
possible organisational solutions
Top ten priorities for dementia
research, limited to prevention,
diagnosis, treatment, and care
17 recommendations on
collaboration infrastructures and
methods, and specific research
topics
Top ten and top 20 research
priorities across seven overarching
research domains

AD=Alzheimer’s disease. CHNRI=Child Health and Nutrition Research Initiative.

Table 2: Priority-setting exercises for dementia research

Conference on Global Action Against Dementia held in
Geneva, Switzerland. Indeed, the identified priorities
provide a sound, balanced research agenda that spans
substantially beyond the G7’s (then G8’s) initial ambitious
goal to identify a disease-modifying treatment for dementia
by 2025.3,27,31 These research priorities can inform policy
makers’ and funders’ decision-making processes globally.
However, to promote a harmonised strategic global
dementia research agenda, further steps are needed,
including a comprehensive landscape analysis of countries
worldwide, a so-called global asset map. This effort should
include the assessment of existing funded research
projects and expenditures by governments and other
funding organisations, and the quantification of patient
participation in clinical research. Such an analysis needs a
harmonised terminology and framework to describe
research domains to allow meaningful cross-national
comparisons, such as the CADRO.15,16 Open data sharing
and strategies centred on improving platforms to
encourage collaboration will facilitate this effort. When
such a harmonised map is compared with the research
priorities identified, gaps and needs could be recognised to
effectively inform the agenda for Global Action Against
Dementia. Nevertheless, the successful implementation of
such a global dementia research agenda needs concomitant
increases in investment, infrastructure development,

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Panel 3: Overview and policy implications of this Policy View
Dementia
• A syndrome characterised by cognitive and functional
decline and behavioural and psychological symptoms, which
is an enormous burden on those affected, their families, and
society, and a recognised global health priority.
Global response
• No nation, in isolation, can realistically respond to the
burden and challenges posed by dementia.
• A fully transparent, systematic, rigorous, replicable, and fair
process that is globally representative and involves all
relevant stakeholders is needed to identify research priorities,
which will inform the global dementia research agenda to
effectively respond to the dementia crisis.
• By focusing resources on established research priorities, the
global burden of dementia could be reduced by 2025.
Dementia research priorities
• The WHO dementia research prioritisation project identified
59 thematic research avenues, which were scored and ranked
according to five criteria.
• Specific research avenues (ie, questions) identified as
priorities for research were drawn from several research
domains, from prevention, identification, and reduction of
dementia risk, through delivery and quality of care for people
with dementia and their carers, to improved diagnosis and
treatment development.
• Basic research into disease mechanisms might have the
greatest potential for conceptual breakthrough in the
specialty.
Strengths and limitations
• Dementia research priorities were identified by over
300 participants from up to 39 countries (20 high-income
countries and 19 low-income and middle-income countries)
capacity building, and international partnerships. Any
such collective efforts will need rigorous and continuous
monitoring of the expected progress. WHO is working on
a Global Dementia Observatory that will function as an
international surveillance platform to support evidence-
based service planning and strengthening of policies, as
well as health and social care systems, across various major
strategic domains, including research. The 139th Executive
Board of WHO decided in May, 2016, “to request the
Director-General to develop with the full participation of
Member States and in cooperation with other relevant
stakeholders a draft global action plan on the public health
response to dementia, with clear goals and targets”.32 Such
a plan would facilitate the implementation and monitoring
of progress and benefits of preventive, diagnostic,
treatment, and care strategies for dementia, and their
coverage within and across countries. In the short term,
policy makers are urged to promptly tackle the persistent
www.thelancet.com/neurology Vol 15 November 2016
Policy View
according to explicit priority criteria, applying the rigorous
Child Health and Nutrition Research Initiative method, which
limits the effects of personal interests or biases.
• 201 of 1386 potential participants responded in the
elicitation of research questions, and we cannot rule out the
presence of response bias (eg, through self-selection).
Response rates at this stage were highest among clinicians
and researchers, and lowest in southeast Asia and African and
eastern Mediterranean regions. Cultural, regional, and
system-level differences in dementia priorities are not known.
Policy implications
• Funders and policy makers should make use of the
59 research priorities identified in this exercise to allocate
resources and investments on a global scale. An upscaling of
research investment should be optimised, accounting for
existing funded research projects and expenditures classified
according to a common terminology and framework to
describe research domains and methods. Established
priorities should be mapped onto the dementia research
landscape to identify existing gaps.
• Efforts are needed by all stakeholders, including WHO, WHO
Member States, and civil society, to continuously monitor
research investments and progress, as well as temporal and
geographical trends in dementia incidence, prevalence, and
burden, through international platforms such as a global
dementia observatory.
• A global dementia action plan should be developed with
clear goals and targets, in consultation with all stakeholders
and informed by sound public health evidence. Such a plan
would facilitate the implementation and monitoring of
progress and benefits of preventive, diagnostic, treatment,
and care strategies for dementia, and their coverage within
and across countries.
Search strategy and selection criteria
We searched MEDLINE, Embase, Google Scholar, and the Cochrane Library, as well as the
internet (using Google and other search engines), for reports of dementia research
priorities or challenges, published between January, 2000, and Dec 31, 2014, with no
language restrictions, before the priority-setting exercise was done. We updated the
search on June 1, 2016, for the Discussion. We developed and adapted our search
strategies by combining PubMed Medical Subject Headings and free-text terms (ie,
“dementia”, “cognitive disorders”, “Alzheimer”s disease”, “vascular dementia”, “Lewy body
disease”, “mild cognitive impairment”, and “challenges”, “goals”, “priorities”, “milestones”,
“roadmap”, “recommendations”, “national strategy and plan”) with PubMed clinical
queries for causative, diagnostic, prognostic, health and social care, and treatment
algorithms. We concentrated on nationwide representative and international reports,
from high-income, middle-income, and low-income countries. Additionally, we hand
searched the reference lists of relevant publications and consulted with experts in the
specialty and other relevant stakeholders, including representatives of patient
organisations, to complement the electronic searches.
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 Policy View
imbalance between the allocation of research funding and
resources, and the unaddressed needs of most of those
who live with dementia worldwide, particularly in LMICs,
where international partnerships should be established
to raise awareness of dementia and improve the
responsiveness of health and social care systems.
In conclusion, even though some of the challenges
highlighted herein might not be attained by 2025, a historic
opportunity now exists to answer research questions in an
unprecedented harmonised and coordinated manner and
on a global scale. This opportunity justifies the pragmatic
optimism expressed by the hundreds of experts and
stakeholders from all world regions who took part in this
exercise that a substantial reduction of the worldwide
burden of dementia can be achieved primarily through
improved prevention and care. An overview and policy
implications from this Policy View are listed in panel 3.
Contributors
HS, EA, CD, IR, KML, and TD, did the survey design and data analysis.
HS and EA wrote the manuscript and contributed equally to its
development and revision. SS and TD developed the conceptualisation
of the study. All authors contributed to data collection, data
interpretation, and review and editing of the manuscript.
Declaration of interests
MR receives funding from Servier. RS has served as a consultant for
Abbvie, Biogen, Bracket, Lundbeck, and Sanofi; and has received
research support from Eli Lilly and Co and Janssen Pharmaceuticals. All
other authors declare no competing interests.
Acknowledgments
KML has received grants from the US National Institute on Aging.
MR is NIHR National Director for Dementia Research and receives
funding from the NIHR Queen Square Dementia Biomedical Research
Unit. RS is a member of the US NIH National Advisory Council on
Aging. We thank the UK Department of Health for the financial support
provided to undertake this work. We also thank all experts and
stakeholders across all world regions who contributed to the original
research questions and scored the thematic research avenues.
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