Advancing Alzheimer’s disease diagnosis, treatment, and care:
Recommendations from the Ware Invitational Summit
Mary D. Naylora,b,c,*, Jason H. Karlawisha,d,e, Steven E. Arnolda,f,g, Ara S. Khachaturianh,
Zaven S. Khachaturianh, Virginia M.-Y. Leea,i,j, Matthew Baumgartk, Sube Banerjeel,
Meryl Comerq, Kenneth Covinskyr, Lynn Friss Feinbergs, Giovanni Frisonit, Colin Greenu,
Renato Maia Guimaraesv, Lisa P. Gwytherw, Franz F. Heftix, Michael Huttony, Claudia Kawasz,
David M. Kentaa, Lewis Kullerbb, Kenneth M. Langacc, Robert W. Mahleydd, Katie Maslowee,
Colin L. Mastersff, Diane E. Meiergg, Peter J. Neumannaa, Steven M. Paulhh, Ronald C. Petersenii,
Mark A. Sagerjj, Mary Sanogg, Dale Schenkkk, Holly Soaresll, Reisa A. Sperlingmm,
Sidney M. Stahlnn, Vivianna van Deerlina,i,j, Yaakov Sternoo, David Weirpp, David A. Wolkg,
John Q. Trojanowskia,i,j
aInstitute on Aging, University of Pennsylvania, Philadelphia, PA, USA
bSchool of Nursing, University of Pennsylvania, Philadelphia, PA, USA
cNewCourtland Center for Transitions and Health, University of Pennsylvania School of Nursing, Philadelphia, PA, USA
dDepartment of Medical Ethics and Health Policy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
eDepartment of Medicine, Division of Geriatric Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
fDepartment of Psychiatry Section of Geriatric Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
gDepartment of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
hPrevent Alzheimer’s Disease by 2020 (PAD 2020), Rockville, MD
iDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
jCenter for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
kAlzheimer’s Association, Chicago, IL, USA
lInstitute of Psychiatry, King’s College London, London, UK
mUniversity of Arkansas for Medical Sciences, Little Rock, AR, USA
nThe Sahlgrenska Academy, University of G€ oteborg, G€ oteborg, Sweden
oSchool of Public Health, University of California at Los Angeles, Los Angeles, CA, USA
pUniversity of Iowa, Iowa City, IA, USA
qGeoffrey Beene Foundation Alzheimer’s Initiative, New York, NY, USA
rUniversity of California at San Francisco, San Francisco, CA, USA
sAARP Public Policy Institute, Washington DC, USA
tThe National Centre for Alzheimer’s and Mental Diseases, IRCCS Fatebenefratelli, Brescia, Italy
uPeninsula Medical School, University of Exeter, Exeter, UK
vInternational Association of Gerontology and Geriatrics, Brasilia, Brazil
wDuke University Aging Center, Durham, NC, USA
xAcumen Pharmaceuticals, Inc., Livermore, CA, USA
yEli Lilly, Inc., Windlesham, Surrey, UK
zUniversity of California, Irvine, Irvine, CA, USA
aaTufts Medical Center, Boston, MA, USA
bbSchool of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
ccUniversity of Michigan and Veteran’s Affairs Ann Arbor Health Care System, Ann Arbor, MI, USA
ddJ. David Gladstone Institutes, San Francisco, CA, USA
eeInstitute of Medicine, Washington DC, USA
ffMental Health Research Institute, University of Melbourne, Melbourne, Australia
*Corresponding author. Tel.: 215-898-6088; Fax: 215-573-4225.
E-mail address: email@example.com
1552-5260/$ - see front matter ? 2012 The Alzheimer’s Association. All rights reserved.
Alzheimer’s & Dementia 8 (2012) 445–452
ggMount Sinai School of Medicine, New York, NY, USA
hhWeill Cornell Medical College, Cornell University, New York, NY, USA
iiMayo Clinic, Rochester, MN, USA
jjUniversity of Wisconsin, Madison, WI, USA
kkElan, Inc., San Francisco, CA, USA
llBristol Myers Squibb, Inc., Wallingford, CT, USA
mmHarvard Medical School, Boston, MA, USA
nnIndependent researcher, Bethesda, MD, USA
ooTaub Institute, Columbia University, New York, NY, USA
ppUniversity of Michigan, Ann Arbor, MI, USA
Abstract To address the pending public health crisis due to Alzheimer’s disease (AD) and related neurode-
generative disorders, the Marian S. Ware Alzheimer Program at the University of Pennsylvania held
a meeting entitled "State of the Science Conference on the Advancement of Alzheimer’s Diagnosis,
markers; Clinical Care and Health Services Research; Drug Development; and Health Economics,
Policy, and Ethics. The workgroups shared, discussed, and compiled an integrated set of priorities,
recommendations, and action plans, which are presented in this article.
? 2012 The Alzheimer’s Association. All rights reserved.
Keywords:Alzheimer’s disease; Neurodegenerative disorders; Dementia; Research priorities; Policy priorities; Health policy recommendations
1. Alzheimer’s disease–A growing crisis
The aging of populations globally has precipitated a de-
mographic “sea change” that is having a profound impact on
societies worldwide and is the most powerful driver of the
increase in age-related disorders, including Alzheimer’s dis-
ease (AD) and related neurodegenerative disorders. Ad-
dressing these changes is among the most important
challenges facing scientists, health-care providers, policy-
makers, the business community, and governments world-
To address the pending public health crisis due to AD and
related neurodegenerative disorders, the Marian S. Ware
Alzheimer Program at the University of Pennsylvania held
a meeting entitled “State of the Science Conference on the
Advancement of Alzheimer’s Diagnosis, Treatment and
Care,” on June 21-22, 2012. The meeting comprised four
workgroups focusing on Biomarkers; Clinical Care and
Health Services Research; Drug Development; and Health
Economics, Policy, and Ethics—all of which must be ad-
dressed simultaneously. The intent of the Ware Summit
was to develop both cross-cutting and domain-specific rec-
ommendations for a range of stakeholders, including the sci-
entific community, policymakers, legislators, advocacy
groups, and clinicians. Toward this end, each workgroup
liminary set of recommendations (Appendix 1). At the con-
ference, these recommendations were shared, discussed, and
compiled into an integrated set of priorities, recommenda-
tions, and action plans, which are presented in this work.
While the four workgroups each developed focused rec-
ommendations reflecting their individual perspectives
(Appendix 2), they reached remarkable consensus on the
core principles and priorities that must be addressed both
short and long term. Attention to these issues would enable
us to provide good quality care for affected patients and
families, advance our understanding of the pathophysiology
and natural history of AD and other dementias, develop ef-
fective treatments to slow or prevent these diseases, and
translate scientific advances successfully into policy and
practice. The overarching goals identified at the Ware Sum-
mit (Table 1) mirror those reflected in the United States
National Plan to address Alzheimer’s Disease (USNPAAD,
or the “National Plan”) , released May 15, 2012 by the
U.S. Department of Health and Human Services (DHHS)
as part of the National Alzheimer’s Project Act (NAPA).
The National Plan outlines a comprehensive approach of
prevention and treatment for AD by 2025.
Recognizing the urgency of the challenges faced by the
Alzheimer’s field as well as the population at large, the rec-
ommendations outlined in this study call for a numberofim-
mediate policy changes as well as introduction of legislative
term changes in efforts to address the oncoming public
health challenges. These recommendations should provide
a catalyst to drive research planning, develop alternative
2. Core principles
Underlying these recommendations are several core prin-
ciples intended to advance the clinical delivery of care and
scientific understanding of AD and related disorders. Efforts
to link science with care and engaging the participation of
patients, families, scientists, pharmaceutical companies,
regulatory agencies, and advocacy organizations were
seen by conference participants as path-breaking and
M.D. Naylor et al. / Alzheimer’ s & Dementia 8 (2012) 445–452 446
instrumental in developing better outcomes for people with
AD as has been demonstrated for cardiovascular disease, di-
abetes, and cancer. The Alzheimer’s field should learn from
and expand on this model, keeping in mind the need to:
? Integrate,butnotduplicate,services, resources,and re-
search, including building on existing infrastructure
where appropriate (e.g., resources available across
institutes at the National Institutes of Health [NIH],
Veteran’s Administration, Center for Medicare and
[CDC], Food and Drug Administration [FDA], and the
Department of Defense [DoD]).
? Shift resources and care delivery to the community and
both medical and social interventions along with re-
search and training to improve the lives of people
with AD and their families.
? Increase awareness among the public, health-care pro-
viders, and policymakers.
? Deliver cost-effective diagnostics, treatments, and ser-
? Engage patients, family caregivers, and advocacy
groups in the decision-making process.
? Focus on affected persons and their families across the
trajectory of AD disease. This requires a better under-
? Focus on drug development and biomarker research
with an aim toward reducing the incidence and pro-
gression of dementia.
? Ensure that addressing dementia is a priority across all
segments of societies and governments both nationally
The complete list of recommendations made by the
four individual workgroups is given in Appendix 2. These
have been reorganized and integrated to address the goals
outlined in Table 1. Recommendations across all work-
groups and goals are compiled in Table 2, with the highest
priority recommendations noted. In making these recom-
mendations, conference participants considered both the
urgency of the public health challenges facing the nation
and world as well as the reality of shrinking federal bud-
gets. Yet, despite the challenging funding environment,
there is an undeniable need for increased investment for
Alzheimer’s research, including basic, translational, clini-
cal, and health-services research, and attention to care-
3.1. Identifying and developing novel treatments that
ameliorate or prevent AD within the next decade
The effort to develop disease-modifying therapies for AD
has reached a crisis  and finding a path forward to over-
come this impasse will require the collaborative efforts of
the research, clinical, pharmaceutical, and regulatory com-
munities, as well as policymakers, to identify barriers and
has been a shift in thinking about the treatment of AD, away
from the possibility that a single drug could ameliorate the
disease. Today, there is increasing recognition of the com-
plexity of the disease, the likelihood that multiple treatments
will be needed at different phases of the disease, and that
treatment will require more than drugs. Toward this end,
one of the highest priorities is to better understand the path-
ophysiology of AD and related disorders by broadening the
research focus to encompass cardiovascular, metabolic, and
inflammatory diseases, all of which play important roles in
the development of dementia.
Biomarkers have become essential tools in drug develop-
ment, both for enriching study populations with subjects
likely to respond to the drug and for monitoring response
to treatment. Objectively monitoring changes in AD is ex-
tremely valuable, but may not be sufficient for monitoring
progression of disease pathology or neurodegeneration per
se. Biomarkers that separate AD and AD dementia from
other aging-related dementias would also be valuable.
In contrast to early-onset familial AD, the far more com-
mon and sporadic late-onset AD (LOAD) is a multifactorial
disease intermixed with universal senescent processes. Fre-
quently, other common pathologic conditions, such as vas-
cular disease or other proteinopathies due to a-synuclein
or TAR DNA protein binding 43 (TDP-43), which are char-
acteristic of Parkinson’s disease (PD) and frontotemporal
degeneration (FTD), respectively, coexist with AD in the
same patient. At present, we do not have biomarkers to dif-
ferentiate these conditions, quantify the relative contribu-
tions of different disease processes, or measure how active
any one might be relative to another. In addition, new bio-
markers that assess other aspects of the disease, such as syn-
aptic function and inflammation, are needed to improve
prediction beyond what is available now, to determine con-
tributions from other diseases, and to better assess disease
Overall goals identified at the Ware Invitational Summit
1. Identify and develop novel treatments, including non-pharmacologic treatments for AD within the next decade, while continuing to focus on
ameliorating or preventing AD.
2. Improve the efficiency and knowledge gained from clinical trials.
3. Enable better patient options through earlier identification of individuals at risk for AD or those in whom the neurodegenerative process has already begun.
4. Provide high-quality, cost-effective, and ethical care to persons with dementia and their family members across the trajectory of the illness.
M.D. Naylor et al. / Alzheimer’ s & Dementia 8 (2012) 445–452447
progression and treatment efficacy. Biomarkers that indicate
the degree of disease or neurodegeneration at any given
point after diagnosis could help guide treatment and assess
treatment effectiveness in clinical trials.
The current situation for the pharmaceutical industry to
bring a new medical entity (NME) to market is both expen-
sive and extremely long, with the average time now esti-
mated to be 10 to 12 years and the cost about $1.8 billion
and rising rapidly . More importantly, however, a series
of patent expirations on blockbuster drugs and a dwindling
drug pipeline hasresulted in a dramatically weakened indus-
try, which could also adversely affect public health efforts to
control AD. Drug discovery may need to transition to a new
model where discovery and early development of well-
defined therapeutic products emanates from academic or
nonprofit institutions, or small biotechnology companies
. In this framework, federal money will help leverage
and launch new public-private partnerships, similar to the
AD Neuroimaging Initiative (ADNI) , and could also
play important roles in filling the precompetitive space .
Goals and recommendations
Goal Priority recommendationsFurther recommendations
Identify and develop novel treatments, including
non-pharmacologic treatments for AD within
the next decade while continuing to focus on
ameliorating or preventing AD.
Increase NIH grant support for research on
understanding AD disease mechanisms and
identifying new AD drug discovery targets by at
Effect revisionsof the regulatory process in orderto
speed the translation of research discoveries into
clinical practice and incentivize industry to
develop AD drugs, including consideration of
alternative clinical endpoints.
Establish the relationship between biomarkers and
cognitive and functional markers.
Complete standardization and validation of existing
biomarkers of interest.
Incorporate AD biomarker assessment into all AD
clinical trials, including those targeting early
Expand longitudinal studies that use standardized
protocols and include multiple biomarkers to
include subjects that better reflect the general
Establish a national/international population-based
registry of older adults with and without
dementia, including geographically and
culturally different populations and individuals
with comorbid conditions.
Develop a risk stratificationmodel that incorporates
demographic, genetic, biologic, cognitive, and
Develop new biomarkers, especially those that
TDP-43, vascular disease, a-synuclein).
Develop better cognitive and functional markers of
the early stages.
Improve the efficiency and knowledge gained
from clinical trials.
Urge all clinical trials involving older patients to
include cognitive markers and AD biomarkers as
part of their assessments.
Require data from clinical trials of both drugs and
biomarkers, including Phase IV data, to be
placed in a shared database to ensure that lessons
learned are shared within the AD research
Enable better patient care through earlier
identification of individuals at risk for AD or
those in whom the neurodegenerative process
has already begun.
Conduct longitudinal population-based studies to
clarify the natural history of AD and other
dementias using clinical measures, cognitive
Establish a detection and treatment regimen for
preclinical AD individuals.
Develop best practice standards on when to order
biomarker test, what and how to disclose and
Develop a training and certification program for
conducting biomarker tests, interpreting data,
communicating biomarker data, and quality
sets for families and clinicians.
Consider legislation requiring that, until the clinical
value of biomarkers is fully understood,
information gained through biomarker studies
cannot be considered in insurance or
of proven effective and efficient care models for
people with dementia and their families.
Provide high-quality, cost-effective, and ethical
care to persons with dementia and their family
members across the trajectory of the illness.
Increase NIH and other sources of support to
advance person- and population-centered, high-
Conduct health services research on diverse
delivery models, including a full assessment of
existing best practices, such as the Program of
All-Inclusive Care for the Elderly (PACE),
palliative care, and international models.
Review and propose appropriate revisions to
existing laws, institutions, and social
structures—such as employers, insurers,
housing, and schools—to assure that they will
protect the rights and interests of persons who
have had an AD biomarker test or other test that
places them at high risk of developing AD.
M.D. Naylor et al. / Alzheimer’ s & Dementia 8 (2012) 445–452448
liorate AD within the next decade include:
? Increasing NIH grant support for research on under-
standing AD disease mechanisms and identifying
new AD drug discovery targets by ?$50 million/year.
? Developing new biomarkers, especially those that
reflect current disease activity (synaptic integrity,
TDP-43, vascular disease, a-synuclein).
? Developing better cognitive and functional markers
sensitive to change in early stages.
? Establishing the relationship between biomarkers and
cognitive and functional markers.
? Exploring revisions of the regulatory process to speed
the translation of research discoveries into clinical
practice and incentivize pharmaceutical companies to
develop AD drugs.
3.2. Improving the efficiency and knowledge gained from
Recent disappointing clinical trials of AD pharmacologic
treatments have slowed new investment into AD drug devel-
opment. Regardless of whether drug trials currently under-
way demonstrate efficacy, there is a growing consensus
within the AD clinical research community that clinical tri-
gathered inthese trials mustbecarefullyanalyzed toprovide
lessons for future drug development. It is essential to im-
prove research and development (R&D) productivity by in-
of success, and by decreasing Phase II and III attrition , or
by changing the current regulatory paradigm. For example,
neurodegenerativedisease biomarkers provide new opportu-
nities to shorten the length of clinical trials so that they do
not consume the period of exclusivity on a new drug. Con-
cerns regarding the length of clinical trials have been com-
pounded by patent law changes that will take effect in
the lengthy product approval process.
Public-private partnerships, such as ADNI, have proven
to be effective models for collecting and sharing data in pre-
competitive space. ADNI and its international partners
(Worldwide ADNI), as well as the Alzheimer’s Biomarker
Standardization Initiative (ABSI)  and the Alzheimer’s
Association’s Global QC program for AD CSF biomarkers
, have also led the way in standardization and validation
of biomarkers, and this process should be completed. Inter-
national standardization of AD biomarkers could impact the
field in much the same way that standardization of choles-
terol or hemoglobin A1c measurement led to widespread
use of these tests in clinical trials and the discovery and
development of effective treatments for cardiovascular dis-
ease and diabetes.
Because cognition is currently thought to be the most
clinically relevant characteristic of the disease, it is also im-
perative that more sensitive and specific cognitive and func-
tional markers be identified, standardized, validated, and
correlated with other biomarkers across the continuum of
the disease process, and that these cognitive markers are
also incorporated into all clinical trials. Moreover, data col-
lected in these trials can prove extremely valuable in plan-
ning future drug discovery efforts, and should be made
available to other researchers, with appropriate compensa-
tion for sponsors (e.g., prompt release of clinical data from
placebo-treatment groups). Recommendations aimed at im-
proving the efficiency of and knowledge gained from clini-
cal trials include:
? Completing standardization and validation of existing
biomarkers of interest.
? Incorporating AD biomarker assessment into all clini-
cal trials of disease-modifying and symptomatic AD
? Urging all trials involving older patients to incorporate
cognitive and functional markers and AD biomarkers
as part of their assessments.
? Expanding longitudinal studies that use standardized
protocols and include multiple biomarkers to include
subjects that better reflect the general population.
? Requiring data from clinical trials, including Phase IV
data, to be placed in a shared database to ensure that
lessons learned are shared within the AD research
erty rights of sponsors.
3.3. Enabling better patient management through early
There is a growing consensus in the AD clinical research
community of the need to identify individuals at risk for AD
or those in whom the neurodegenerative process has already
begun [8–11]. New diagnostic criteria proposed by three
workgroups convened by the National Institute on Aging
in partnership with the Alzheimer’s Association (NIA-AA)
[12–15], as well as by an International Working Group
(IWG) , recognized the value of incorporating bio-
markers of AD and neurodegeneration in research studies,
but concluded that they have not been sufficiently standard-
ized or validated for use in clinical care. The field is rapidly
moving forward, with the goal of using biomarkers to ascer-
tain AD as a diagnosis of inclusion with a level of certainty,
rather than a diagnosis to be made after excluding other
disorders. However, the consensus at this time is that the sci-
ence does not support the widespread clinical application of
a biomarker-based diagnosis.
The NIA-AA committees distinguished three stages of
disease: (1) a preclinical phase, where the pathophysiologic
processesofADhavebegunbefore anyevident signsofcog-
nitive impairment; (2) a prodromal or MCI due to AD phase,
where there is evident decline in memory or other cognitive
functions; and (3) AD dementia, where cognitive and
M.D. Naylor et al. / Alzheimer’ s & Dementia 8 (2012) 445–452449
individual needs help with activities of daily living.
Although substantial data indicate that leading cerebro-
spinal fluid (CSF) and neuroimaging biomarkers provide
clinically useful information for patients with evident cogni-
tiveimpairment (i.e., mild cognitiveimpairment and demen-
use of AD biomarkers in asymptomatic individuals .
abnormal CSFAb levels or Ab on positron emission tomog-
raphy (PET) scans; however, it is not yet known whether ab-
normal AD biomarkers in asymptomatic people indicate
adisease process thatwillmanifestasmild cognitiveimpair-
ment (MCI) and AD at some future point and, if so, when.
Although ADNI has been extraordinarily successful in iden-
tifying, standardizing, and validating biomarkers, the popu-
lation studied does not necessarily reflect the general
population. Thus, to establish appropriate biomarker cutoffs
for both clinical trials and clinical usage, it is imperative to
conduct longitudinal, population-based studies with stan-
dardized protocols and multiple biomarkers and cognitive
markers. Establishing aninternationalpopulation-basedreg-
istry of older adults, including geographically and culturally
different populations and individuals with comorbid condi-
tions, is thus a high-priority recommendation from this con-
ference . This registry could take advantage of existing
clinical databases such as those managed by the Department
of Veteran’s Affairs and the Center for Medicare and Medic-
aid Services, and could be modeled after other large longitu-
dinal studiessuchas the
Cardiovascular Health Study, the Health and Retirement
Study, and other population-based studies of aging (summa-
rized in Ref. ).
Using biomarkers to define risk, however, presents sev-
eral concerns, particularly because a therapy that impacts
an AD biomarker is not certain to translate into clinically
meaningful endpoints . The experience of other
biomarker-based processes demonstrates the need for cau-
tion in disseminating a biomarker into clinical practicewith-
out clarifying its value . Clinicians do not yet have
a good way to predict the future of AD, including the speed
of progression and the extent that function will be affected.
If an effective disease-modifying therapy is reported, re-
search needs to address how it will change AD. In particular,
as ongoing and planned research enhances our understand-
ing of the preclinical stages of AD, both how we think about
the disease and its treatment will change. What was once
a disease defined by clinical signs and symptoms, with treat-
ments designed to reduce these clinical features, will be-
come a disease defined by the risk of developing these
signs and symptoms, and once they occur, their risk of wors-
ening. The concept of successful treatment (including non-
pharmacologic treatment) will then be transformed to
mean reducing risk and improving quality of life, and it
is shown to be both clinically meaningful and cost effective.
As the value of biomarkers and other risk factors
emerges and becomes clinically useful, patients and society
will be better served if we think of biomarkers not as labels
of a category, such as “preclinical AD,” but rather as one,
yet not the only, measure of risk for disability as a result
of progressive cognitive decline. To make the best use of es-
tablished and emerging biomarkers and other risk factors for
AD, a major goal of the AD research community should be
to develop and validate a risk-stratification model for the de-
velopment of endpoints, such as MCI or dementia, to guide
1) clinical and care management decisions by patients, fam-
ilies, and health-care providers; 2) policymaking; and 3) re-
search to test new interventions. Such a risk-prediction
model, which incorporates drugs, clinical trials, and bio-
markers , holds substantial promise for improving pub-
lic health. Moreover, it is possible that certain biomarkers
will ultimately identify individuals who will progress to
AD and hence prove critically important for identifying
early treatment and intervention strategies as these emerge,
akin to how a Pap smear is currently used to identify women
at risk of cervical cancer. The Economics, Ethics and Health
Policy Workgroup drew on their collective expertise in both
neurodegenerative diseases and other diseases of aging,
such as cardiovascular disease, osteoporosis, and cancer,
to propose how the promise of this risk-based model can
The risk-stratification model should be developed using
data from representative population-based samples so as to
accurately represent the clinical complexity of typical older
adults, and the resulting competing health risks (e.g., heart
disease, diabetes, cancer) that may have a major impact on
and value of drug and other interventions to prevent or treat
AD. Further, the risk-stratification models should be in the
public domain, and should be evaluated and updated by
a public body (e.g., DHHS) using established standards for
the reliable and valid measurement of AD risk factors, in-
cluding the standardization of AD biomarkers. The ongoing
evaluation of risk-stratification models should include as-
sessments of the costs (e.g., from unnecessary treatment
and treatment side-effects) that result from misclassification
when using the models. Recommendations aimed at en-
abling better patient care through early identification in-
? Establishing a national/international population-based
registry of older adults, including geographically and
culturally different populations and individuals with
? Conducting longitudinal population-based studies to
clarify the natural history of AD and other dementias
using clinical measures, cognitive tests, and bio-
? Developing best practice standards on when to order
the biomarker test, and what and how to disclose and
M.D. Naylor et al. / Alzheimer’ s & Dementia 8 (2012) 445–452450
? Developing a training and certification program for
conducting biomarker tests, interpreting data, commu-
nicating biomarker data, and quality assurance.
? Developing a risk-stratification model that incorpo-
rates demographic, genetic, biologic, cognitive, and
environmental risk factors.
3.4. Providing quality, cost-effective, and ethical care to
persons with dementia and their family members
AD and other dementias represent the most urgent prob-
lem facing the aging population, but these health challenges
exist within the larger context of aging, multiple morbidity
and resulting disabilities, and social risks. Providing good
quality and cost-effective care to persons with dementia
and their families means providing care across the contin-
uum of the illness, beginning at the “something-is-wrong”
stage. This will require accelerating advances in knowledge
and policy that would foster care-delivery systems more
closely aligned with people’s needs throughout their health
and illness trajectories, a better understanding of current
best practices, and developing and implementing new strat-
egies to build and expand the workforce capacity to create
and support a high-value care system for people with AD
and their family caregivers.
Cognitive impairment in combination with other acute
and chronic illnesses complicates the care of patients, al-
though the precise effect of coexisting chronic conditions
onhealth-care utilization anddelivery isnotwell understood
. A truly responsive health-care system needs to address
the needs of family members and other caregivers along an
individualized and changing illness trajectory and in multi-
ple contexts. As people move along this continuum, their
needs become more complex often because many chronic
problems are progressive in nature. In addition, limited so-
barriers, financial limitations, and other factors may exacer-
bate the nature and intensity of these needs.
Bringing care to persons with dementia and their families
can best be realized by integrating in one place health-care
and social services as well as research and training pro-
grams. Numerous models for such community-based
health-care delivery exist internationally, including, in the
United States, the Program of All-Inclusive Care for the El-
derly (PACE), and various palliative-care programs. The
best of these programs join proactively with community
partners to enable preservation of cognitive and physical
health through primary prevention strategies such as public
health awareness programs and fitness training .
To identify the model that best fits the needs of patients
with dementia and their families, health services research
is needed to explore diverse delivery models and their appli-
cability at different stages of illness and with different levels
of family need and capability. These care models then need
to be tested with regard to their effects on key clinical and
utilization metrics within the overall population and among
different subgroups. Further, there is a need to better under-
stand the goals identified as most meaningful by the people
served—an enhanced care experience, improved health and
quality of life, and/or survival—while choosing wisely with
finite resources .
Following the identification of best practices, there will
be a need to integrate these priorities into the DHHS/
NAPA National Plan and articulate the value proposition
to key stakeholders, including governmental organizations,
legislators, advocacy groups, and the public at large. Techni-
cal assistance skill sets designed to meet the needs of pa-
tients, families, and clinicians can be developed to speed
implementation of best practices into the community.
tion of their rights and interests, attention to issues, such as
stigma, and protection against possible misuse of clinical in-
formation, including results from biomarker tests and risk
assessment. Thus, we recommend review and possible revi-
sion of existing laws that pertain to institutions and social
structures (such as insurance and employment) to ensure
protection of patients and their families. Recommendations
to ensure quality, cost-effective care, and ethical care to per-
sons with dementia and their family members include:
? Conducting health services research on diverse deliv-
ery models, including a full assessment and dissemina-
tion of evidence-based current best practices.
? In order to protect the rights and interests of patients
who have had biomarker testing and to prevent misuse
revisions are needed of existing laws, institutions, and
? Legislation should be considered immediately that,
until the clinical value of biomarkers is fully under-
stood, information gained through biomarker studies
cannot be considered in insurance or employment de-
The goal of the Ware Invitational Summit on the Ad-
vancement of Alzheimer’s Diagnosis, Treatment, and Care
was to formulate a set of recommendations that will inform
efforts around the world to address the escalating AD public
health crisis. This study represents the work of a multidisci-
plinary group of researchers, advocates, and clinicians from
academia, industry, and advocates. These experts first ad-
dressed concerns specific to four different domains: Drug
Development; Biomarkers; Clinical Care and Health Ser-
vices Research; and Economics, Ethics, and Policy. This
group subsequently came together to incorporate their rec-
ommendations into a fully integrated and comprehensive
strategy, which is presented here to the field at large as
well as to individual stakeholder groups, including the lead-
ership ofDHHS/NAPA,the NIH, policymakers,researchers,
clinicians, and advocacy and patient groups.
M.D. Naylor et al. / Alzheimer’ s & Dementia 8 (2012) 445–452451
Implementing many of these recommendations, includ- Download full-text
ing increased research funding, will require creative think-
ing, repurposing of existing funds, vigilance in reducing
waste, and a constant focus on cost effectiveness. The enor-
mity and complexity of AD demands no less.
The authors thank Lisa J. Bain for editorial assistance.
Theauthorsalso thank the Marian S.Ware 2006 CWG Char-
itable Lead Annuity Trust for sponsoring this program.
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