Stroke and Vascular Cognitive Impairment: A Transdisciplinary, Translational

and Transactional Approach

Vladimir Hachinski
Stroke 2007;38;1396-; originally published online Mar 8, 2007;
DOI: 10.1161/01.STR.0000260101.08944.e9
Stroke is published by the American Heart Association. 7272 Greenville Avenue, Dallas, TX 72514
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ISSN: 1524-4628

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 Special Report

The 2005 Thomas Willis Lecture

Stroke and Vascular Cognitive Impairment

A Transdisciplinary, Translational and Transactional Approach
Vladimir Hachinski, MD, FRCPC, DSc

AbstractAdvances in stroke are occurring at an unprecedented pace, but often in disciplinary isolation and without
optimal mechanisms for systematically translating, integrating and applying the findings.
Knowledge accrues in pieces, but is understood in patterns. To optimize knowledge acquisition and application,
infrastructures and systems need to be set up along with appealing incentives. The approach needs to be
transdisciplinary, going beyond the bounds of any given discipline, reciprocally translational, and transactional,
meaning that the interchanges have to yield previously agreed benefits to the parties (The Triple T Approach). A new
breed of leaders needs to be developed and nurtured to catalyze the process.
Opportunities abound. Stroke and most brain diseases share the same pathophysiological fundamental mechanisms.
An integrated, systematic approach to these processes could yield not only greater understanding but new, common
therapeutic targets for several diseases. Biphasic clinical trials could combine the best features of pragmatic and
explanatory, randomized clinical trials. The greatest opportunity of all may be the largely under-explored and
under-exploited borderlands between cerebrovascular and Alzheimer disease. One in three of us will have a stroke,
become demented, or both. For each person who has a stroke or Alzheimer disease, two have some cognitive impairment
short of dementia, often subclinical cerebrovascular disease on a substrate of Alzheimer changes. The fact that
cerebrovascular and Alzheimer disease share the same risk factors, provide a great opportunity for prevention, if
implemented at the brain at risk stage.
Systematically integrating what we know and evaluating what we do could spur progress. Research is not only an
activity but an attitude. Making evaluation and incentives to excel part of the funding of all stroke activities would yield
far ranging cumulative improvements in all aspects of stroke.
No system can replace the individual initiative, creativity and insights that lead to the great discoveries, but progress
is not made by breakthroughs alone. No ones work is so exalted that it cannot be improved, nor so humble that it has
no value. We can all make a difference. (Stroke. 2007;38:1396-1403.)
Key Words: Alzheimer disease clinical trials discovery intervention stroke
treatment vascular cognitive impairment

U nprecedented advances in genetics, proteomics, imag-

ing, informatics, diagnostics and therapeutics stem
partly from the increasing numbers and sophistication of
dedicated researchers. Investigators often push their research
to the limits of their discipline but seldom beyond. This tends
to happen to the detriment of areas that fall between special-
ized interests. Probably subclinical vascular disease is the
most neglected area of all. Our focus has been on clinical,
catastrophic stroke and yet advanced imaging studies suggest
that in 1998 in the United States, 770 000 strokes occurred,
about 9 040 000 so called silent infarcts and 1 940 000
microhemorrhages.1 These usually inflict subtle cumulative
brain damage resulting in cognitive and behavioral changes
and confer a heightened risk for both clinical ischemic and
hemorrhage stroke. Although the deficits from subclinical
events may be smaller compared with obvious stroke, the
public health burden may be greater, because of the substan-
tially larger number of individuals.
One in three North Americans will experience a stroke, be-
come demented, or both.2 For each person over the age of 65
years who has experienced a stroke (8%) or is demented
(8%), two have some cognitive impairment short of dementia

Received December 13, 2006; final revision received January 24, 2007; accepted January 31, 2007.
From the University of Western Ontario, London, Canada.
This article is based in part on the Willis Lecture delivered at the 30th International Stroke Conference in New Orleans, February 2 4, 2005.
Correspondence to Vladimir Hachinski, MD, FRCPC, DSc, Stroke Editorial Office, 100 Collip Circle, Suite 116, London, Ontario, Canada, N6G 4X8.
E-mail stroke@lhsc.on.ca
2007 American Heart Association, Inc.
Stroke is available at http://www.strokeaha.org DOI: 10.1161/01.STR.0000260101.08944.e9

1396
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(17%).3 Vascular cognitive impairment is becoming recog-
nized as a highly prevalent and preventable syndrome.4 Given
the rising number of the elderly worldwide, we must accel-
erate our knowledge acquisition, availability and application,
to successfully confront the looming epidemic of cerebrovas-
cular disease and its drastic and subtle manifestations.
Stroke and associated vascular cognitive decline and Alz-
heimer disease share the same risk factors, and both occur
commonly in the same patients,3 but these two conditions
tend to be studied at the extremes, ie, clinical stroke and
dementia. Probably the most promising time to intervene is
before clinical manifestations appear, the brain at risk
stage.5 This remains a big, under-explored and under-
exploited area for treatment and prevention of stroke and
cognitive disorders.
Although great advances have occurred in prevention and
acute treatment, such as the use of tissue plasminogen ac-
tivator in the treatment of acute stroke, we have not always
managed to bring all the required knowledge together for
optimal results. Witness the long litany of failed acute stroke
neuroprotective trials. Over a thousand drugs and interven-
tions have proven promising in acute experimental stroke, but
only a handful of experimental studies have met minimal
standards for clinical relevance.6
Crucial pieces of a pattern often lie beyond un-
breached disciplinary boundaries. The systematic integration
of existing knowledge, the establishment of common stan-
dards and a synergistic, targeted approach may accelerate the
rate of progress in confronting stroke and related disorders.
Brain Diseases: Common Mechanisms,
Manifold Manifestations
Although the brain functions with infinite complexity, it fails
through common basic pathophysiological mechanisms, such
as excitotoxicity, mitochondrial DNA damage, oxidative stress,
disturbed neurotransmitter release, and apoptosis. These fun-
damental mechanisms underlie not only stroke but also
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Hachinski The 2005 Thomas Willis Lecture 1397
Figure 1. Cartoon based on the story of
the 6 blind men of Hindustan, who
touched different parts of the elephant and
came to very diverse conclusions.
Alzheimer disease, Parkinson disease, epilepsy, amyotrophic
lateral sclerosis, multiple sclerosis among other neurological
disorders (Figure 1).
Although each of these mechanisms has been studied in the
context of each of these diseases, little systematic effort has
been devoted to understanding their common biology. Simi-
larly, mechanisms such as that of the blood-brain barrier, the
microcirculation and the transport and role of different
molecules, too often are studied in isolation. When efforts are
made to bring specialists together, such as in workshops,
participants learn much, return to their disciplinary labors
enriched by the experience with some ideas for collaboration
but with no true incentives or follow-up. Typically, individ-
uals asked to participate in such workshops are well estab-
lished in an area and over-committed, so even given willing-
ness would require a considerable sacrifice of a proven
approach for the uncertainty of transdisciplinary collabora-
tion. And yet, the greatest promise is in integration, focusing
on questions ripe for answers and in synchronizing and
leveraging what knowledge we have. To follow through on a
systematic approach would need to be planned, funded, and
undertaken.
Specialized terminology poses another obstacle to interdis-
ciplinary research because nomenclature varies by discipline.
For example, the trauma literature on carotid dissection
cannot be accessed through PubMed because the term is not
used. Blunt injury to the artery involved would yield a number
of key articles. At the moment, no system exists for accessing
some of the relevant knowledge in an equivalent way.
Broadening Clinical Trials
Although the return on investment in clinical trials is sub-
stantial,7 not enough are done, nor perhaps optimally. Two
major types of randomized clinical trials prevail: the large-
scale simple pragmatic trials, and the smaller-scale intensive
explanatory trials. Advantages of the large trials include
greater ability to generalize, ease of performance, and in
1398 Stroke April 2007
principle are faster. The explanatory trials, with imaging and
other investigations, allow for a better characterization of the
patients and give better grounds for understanding pathophys-
iology and subtypes. Moreover, because these trials are often
carried out in highly qualified selective centers, the results
may be more reliable. On the other hand, trials are increas-
ingly cumbersome and expensive, have limitations on gener-
alizing the findings, and at times lack the statistical power to
answer important secondary questions.
Biphasic Clinical Trials (the COMSENS method)
The process of discovery is seldom connected to its applica-
tion although that is often the ultimate aim. Application of
knowledge, on the other hand, often misses the opportunity of
contributing to learning. One example is the large disconnect
between experimental work in acute stroke and its evaluation
in clinical trials.6
Attempts should be made at integrating the best aspects of
both approaches. First, the preparatory experimental work
can be more extensive and interactive. Typically, experiments
are performed on a single strain of rodents, under standard-
ized and optimal conditions, in young animals, and results are
then tested in elderly stroke patients with comorbidities under
heterogeneous conditions, in strokes of diverse etiologies,
causing varying degrees of damage at different times. Drugs
should be tested on a variety of animals under different
conditions with induced comorbidities, such as hypertension
and diabetes, and under the most varying and challenging
conditions. If the drug has an effect despite these confounding
factors, then it clearly has promise for application in humans.
A necessary step between showing efficacy in rodents and
applications in humans is to verify the therapeutic effect in
animals with gyri, the closer phylogentically to humans, the
better.
The animal experiments could then be modeled for possi-
ble effectiveness and tested against a database from the
placebo arm of previous trials. In phase I of the clinical trial,
there should still be a close interaction between the experi-
mental model and the safety and dosage finding studies in
humans. The phase I trial should not be limited to young,
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Figure 2. COMprehensive Synergized
ENtrained Studies (COMSENS).
healthy volunteers, but also to individuals of an age compa-
rable to the ultimate test population. The phase II trial would
initially take place in highly experienced and sophisticated
centers to study inpatients extensively, to include all measur-
able effects, including the neurological status, cognition,
imaging, pharmacokinetics, pharmacogenetics, dynamic im-
aging and other relevant measures, while maintaining close
touch with those who performed the experiments and those
responsible for phase I. Once the protocol has been refined
and safety monitoring measures implemented, then a simpli-
fied protocol could be developed for the use of a large number
of centers that, in addition to regular monitoring, would have
statistically valid audits to ensure both adherence to the
protocol and that the patients entered in the larger centers are
comparable to those being studied at the smaller centers. The
simplified protocol would facilitate entering more patients of
diverse ethnicity, socioeconomic status and settings. Patients
would continue to be entered in both types of centers. When
an end point is reached, conditional approval would be sought
and a further simplified version of the protocol would
continue, focusing on the efficacy and safety findings of the
main study. This obligatory registry would have its quality
assessed systematically by statistically valid audits (Figure 2).
Cognition as an Outcome Measure
Cognitive impairment may be the earliest, commonest and
subtlest manifestation of cerebrovascular disease. Elias et al
found an inverse correlation between the Framingham stroke
risk score and the presence of abnormalities in executive
function.8
Consequently, selective cognitive tests could be a more
sensitive primary outcome measure than stroke, myocardial
infarction and vascular death for prevention studies and the
Rankin Score for acute trials. One sixth of patients have
cognitive impairment before9 and one third after an acute
stroke.10
Cognitive competence contributes to quality of life and
cognitive impairment represents the most important factor in
determining institutionalization three years after a stroke.

Cognitive impairment is a more powerful predictor than age
and physical impairment.11
One previous obstacle to the use of cognitive measures has
been the time it takes to administer the tests. Recently, a
5-minute screening battery has been recommended. If posi-
tive, a standard 30- or 60-minute battery can be used to define
more precisely the nature and extent of the cognitive impair-
ment.4 Cognitive impairment can be quantitated. Dementia
is a coarse, end stage, yes or no measure that requires a
large sample size and obscures the different types and degrees
of cognitive impairment that correlates with quality of life
and self-sufficiency measures.
Patients with cognitive impairment are either excluded or
not identified in clinical trials. Hence, we do not know the
relative response of these patients to our common treatment
modalities such as antihypertensive agents, antiplatelets,
agents, statins, oral anticoagulants, carotid endarterectomy
and tissue plasminogen activator. The answer may not be the
same for each modality nor the directional effect of the
treatment obvious. Patients with cognitive impairment could
benefit less because of lesser or deleterious effects, or more
because being at higher risk could reap greater benefits from
the treatments. This represents another area of opportunity for
further research.
Clinical Trials: Challenges and Opportunities
Clinical trials in uncommon conditions pose a special chal-
lenge. One way to evaluate unproven interventions in less
common types of strokes is to link reimbursement to partic-
ipation in a study: for example, the use of intra-arterial tissue
plasminogen activator for the treatment of basilar artery
occlusion. A convergent stepwise approach12 has been sug-
gested. Each center would define a priori which patients
they would be willing and unwilling to treat and abide by
their criteria. Data and outcomes on all the patients would be
documented. An external blinded monitoring committee would
determine which categories of patients have such a bad outcome
that treatment cannot be justified and which have such good
outcome that intervention becomes unnecessary.
The process would be reiterative, whereby the categories of
patients where treatment is demonstrably useless, harmful or
unnecessary would be reduced in a stepwise convergent
fashion. A randomized clinical trial could then be justified in
patients in whom the results of treatment remained uncertain.
A similar approach could be used for purported treatments
of carotid and vertebral artery dissection, moya-moya, central
nervous system vasculitis, in stroke prevention and rehabili-
tation trials as well as in other fields.
Clinical trials contribute important answers because they
either show an intervention to work or do not, in the latter
case saving money and potential injury to patients. Clinical
trials in stroke sponsored by the National Institute of Neuro-
logical Disorders and Stroke (NINDS) have repaid the invest-
ment handsomely.7,13
The increasing merger of drug and devices companies
creates the opportunity for doing factorial design studies
because the portfolio of the merged company may contain
several potentially complementary interventions. The facto-
rial design allows for the evaluation of two treatments
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Hachinski The 2005 Thomas Willis Lecture 1399
simultaneously and of their potential interaction. Another
possibility lies in a drug or device company sponsoring a
randomized clinical trial to test one of their products and a
governmental, volunteer or other nonprofit organization pay-
ing for the additional cost of a factorial design to test a
generic treatment, such as the best dose of acetylsalicylic
acid.
Networks of excellence in all aspects of stroke, such
as the Canadian Stroke Network (CSN; http://www.
canadianstrokenetwork.ca) and the consortia of academic
and community clinical trials investigators such as the Cana-
dian Stroke Consortium (http://www.strokeconsortium.ca/)
and the National Institute of Health Sciences specialized
program in Translational Research in Acute Stroke
(SPOTRIAS; http://www.spotrias.com/) are steps in the right
direction toward integrating research and its application.
Many more physicians in practice may become involved in
clinical trials. In 2005 the NINDS launched a Clinical Research
Collaboration (CRC) project whereby hundreds of practice-
based and academic-based neurologists will become part of an
investigators network linked through a web-based CRC coordi-
nating center (https://secure.emmes.com/crc/home.htm).
In the future, clinical trials probably will be larger with
simpler designs and include measures of cognitive outcomes,
disability scales and quality of life outcomes.13 Trials in the
future may also use a greater variety of designs. An adaptive
design trial allows for early stopping of the study if the
criteria predicting success fails to be met.14
Probably, therapy will become individually tailored15 and
patients will play a greater role in setting outcomes. A goal
attainment scale instrument has been proposed. Through it,
individuals set their own goals according to their needs and
state improvement or worsening in their own worlds.16
Whatever shape clinical trials will take, they will likely
remain mainstays of progress.
A Transdisciplinary, Translational,
Transactional (Triple T) Approach
Individually initiated and driven research is being com-
plemented by large-scale collaborations. The Genome Project
represents a massive and successful example of integration of
knowledge, as is the ongoing International HapMap Project.17,18
The Road Map of the National Health Institutes19,20 also marks
an innovative step, but the translational research budget may not
exceed 1% to 2% of the $29 billion total budget.21
The American Stroke Associations Bugher Foundation
competition to fund three interactive centers in stroke pre-
vention may be an auspicious beginning to integrate and apply
knowledge in stroke (http://www.americanheart.org/presenter.
jhtml?identifier2530). The subspecialized, reductionistic ap-
proach has been highly successful and needs to be continued but
as part of a larger, interactive, synergistic system.
Undeniably, experimental, longitudinal, clinical and out-
comes studies continue to make major contributions to
understanding stroke. Each approach has its advantages and
limitations. Longitudinal epidemiological studies provide in-
valuable data on the natural history on a number of vascular
risk factors and their relationship to stroke, Alzheimer disease
and vascular cognitive impairment. However, they seldom
1400 Stroke April 2007
address mechanisms, and without an understanding of patho-
physiology, the results can be misleading. Hypertension has
emerged as the single most powerful predictor of stroke and
its relationship to salt intake has been raised. Physiological
studies show that for some individuals, high salt consumption
contributes to their high blood pressure, and in others, high
salt consumption reflects the need to maintain their blood
pressure. In a population with both types of individuals, in
equal proportions, an epidemiological study would find no
association between salt consumption and blood pressure.22
Similarly, for many years, the epidemiological studies
showed a strong relationship between high cholesterol and
coronary disease but no such association between high
cholesterol levels and the risk of stroke,23 despite atheroscle-
rosis being a leading cause of stroke. It took studies that
subdivided stroke into those attributable to atherosclerosis
from those arising from hypertensive small vessel disease,
and cardiac embolism and the discovery that stroke itself can
temporarily decrease the blood levels of lipids24 from recum-
bence,25 to show a relationship between high lipid levels and
stroke, now widely accepted.26
These observations imply that epidemiological data can
best be interpreted in close relationship to clinical and
experimental work, and that considerable knowledge can be
gained by systemically evaluating, applying and interpreting
knowledge in the different disciplines as it grows. Clinical
trials often provide valuable data about the natural history of
diseases and conditions and can also yield useful information
regarding their mechanisms.
Administrative databases that document stroke, and other
conditions in hospitals, clinics and offices give a glimpse of
the condition in the real world and paint a more realistic
picture of what happens to stroke patients outside of clinical
trials. Several provinces in Canada keep extensive databases27
on all users of the medical care system including admissions,
procedures, prescriptions and outcomes. For patients partici-
pating in studies, it is possible, with their permission, to
continue to follow them for major outcomes indefinitely.
Clinicians and trialists most often work from established,
well-equipped and experienced centers on a selective popu-
lation focusing on individual patients. Although trialists often
will stratify for center size and other known parameters,
typically, they do not measure the impact of medical infra-
structures and systems of care, which can have as much
influence on outcomes as the medical interventions them-
selves. For example, in Canada an inverse relationship
emerged between the size of the centers looking after stroke
patients and mortality and quality of care.27
A systematic integration of experimental, longitudinal
studies, clinical trials and administrative databases, would
yield an amplified database suitable for generating hypothe-
ses and allowing modeling. The hypotheses and models could
then be tested by the most appropriate experimental studies,
longitudinal studies, clinical trials and health outcomes re-
search or combinations of the above (Figure 3).
Such an IdeA center would call for a team of complemen-
tary talents working from diversity and fragmentation toward
convergence and integration. The team would use not only
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Figure 3. IdeA stands for idea and data acceleration center. An
actual and virtual team of complementary talents, working on
commonly agreed problems.
the methodologies of their own disciplines but contract other
necessary ones, and if they do not exist, invent them.
The Marketplace of Knowledge and
Transactional Research
The free enterprise system has probably been the most
successful in developing technologies such as imaging, ther-
apies such as drugs and devices, and in marketing their
products. The profit motive is a great incentive, but it does not
always serve the common good. A large number of drugs
reaching the market offer little additional benefit and much
additional cost compared with available products.28
We should become more aware of the existence of a
medical-industrial complex of mutually self-interested rela-
tionships among researchers, providers and users of medical
knowledge and products, and the extent of its influence.
Much of the research and educational agendas are sponsored
and hence influenced by industry.29 One consequence is that
the emphasis is on drugs, devices and diagnostic technology,
and while welcome in themselves, they probably play a much
larger role than they deserve if cost-effectiveness were the
main criterion.
The industry, regulatory agencies and consumers should
assure a focus on developing and evaluating new therapies
and applying optimally and effectively the existing ones.
Although we must define clear boundaries between com-
monality and conflicts of interest, we have much to learn
from the free enterprise approach. If the identification and
application of new knowledge in a commercial area would be
undertaken, it would not simply rely on researchers to do their
investigations as they wished, but it would begin with a
survey of available knowledge, its quality and promise. The
ideas would be evaluated and tested and mechanisms put into
place to bring the product to market.
In the field of stroke, an orderly, in-depth evaluation of
what is known should be undertaken, interpreting the knowl-

edge from the viewpoint of the multiple, relevant disciplines,
but expressed in common, accessible terms, perhaps in the
language of systems biology (www.sysbiosociety.ca) with the
establishment of a semantic web that can access facts, no-
menclatures and concepts from behind jargon jungles. This
knowledge could be enhanced by taking several long-term
perspectives: How does this knowledge fit in the broader
context of evolution and similar mechanisms in other spe-
cies? What is the natural history of this phenomenon from
conception to maturation and demise? What modulating
effect does age play on mechanisms?30 Do the mechanisms
that lead to the development of the nervous system go in
reverse during degeneration?31 Promising areas could be
identified and parties interested in investing in the answers
could be made aware of the opportunities and the individuals
and centers willing to tackle parts.
The work would need to begin modestly, with dedicated
centers to address a specific question, in all its aspects, with
a strong interactive network with other centers that may
provide parts of the answer, and also with an adequate budget
to allow for contractual work to be performed as part of
seeking an answer. The nature of the exchange and interac-
tion of knowledge could be termed transactional. The rela-
tionship needs to be interactive and bi-directional or multi-
directional, as required and of mutual benefit. The contracts
need not be only monetary, but could be exchanges of
knowledge, scientific credit and other reciprocal advantages.
Relationships must remain voluntary, lest they breed an
oppressive bureaucracy.
Although physicians and scientists are buffeted by external
forces affecting their productivity, they can also become
obstacles to progress by favoring a particular approach. John
Dick, the recent discoverer of cancer stem-cells, recalls how
difficult it was to get funding for his investigations from 1975
to 1995 because the research world was captivated by the
wonder of genes and molecular biology. Cell biology had
fallen by the wayside and stem-cell research was carried
on by a fairly small club of people . . . . laboring in the sha-
dows.32 Stem-cell research itself may become the new hot
thing that could starve funds from other approaches.
It could be argued that in times of scarcity, different
approaches should not be tried, because we know that
focused, specialized methods yield results. We may need to
do the opposite. Precisely because of the rising threat of
stroke and vascular cognitive impairment, we must stem the
tendency for knowledge to grow in increasingly subspecial-
ized areas where further contributions risk becoming part of
a circling pool of limited ideas.
The precise model that would achieve the espoused aims
would need to be piloted and tested empirically, but it could
begin with a center that had at least three components: (1) a
transdisciplinary focus on a promising area of stroke or
vascular cognitive impairment; (2) a team of individuals with
a track record of synergistic collaboration; (3) an educational
program that would educate individuals to focus on problem
solving and to become familiar with the many approaches so
that they can become facilitators and leaders of knowledge
integration.
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Hachinski The 2005 Thomas Willis Lecture 1401
It would take major motivation and considerable incentives
to have successful researchers in one area venture beyond
their expertise, grant and publication success. A legitimate
debate between how much funding agencies should invest in
large-scale, integrated projects, compared with individually
generated research, needs to continue.21 The potential advan-
tages of a Triple T approach is that it is voluntary. Industry
and other users or investors would see faster and better results
from their investments. They may fuel the system with the
most powerful of motives: self-interest. Much knowledge
already exists behind the conceptual and semantic barriers of
subspecialties that seldom talk to each other, and when they
try, often do so from different premises, concepts and
vocabularies. Complementary knowledge is held in thought-
tight compartments within the same subspecialty. If we only
knew what we already know!
A structure for transactional research needs to be set up,
availing itself of the latest information technology and exper-
tise from other fields where some integration has been
successful. The focus should not be so much on acquiring
new bits of information, but integrating what is known, across
disciplines, across methodologies, and formulated in dynamic
and logically sound concepts, with specific formulation of
questions that then can be addressed systematically. The
mere formulation of a problem is far more often essential than
its solution, which may be merely a matter of mathematical or
experimental skill. To raise new questions, new possibilities,
to regard old problems from a new angle requires creative
imagination and marks real advances in science. Albert
Einstein (1879 1955). This may apply most obviously to
the physical sciences, but the principle of formulating a
specific, feasible goal and then finding the best means to
attain applies universally. If you do not know to which port
you are sailing, no wind is favorable Lucius Annaeus Seneca
(5 BC 65 AD).
Enhancing the Availability of Knowledge
The technology for linking and integrating data proceeds
apace. Soon we will have a semantic web. However, data
integration still requires common data formats and identifi-
able vocabularies.33 That remains the task of those who know
the most about the subject matter. The study of cognition as
a manifestation of cerebrovascular disease has been ham-
pered by the lack of common standards of assessment. Now
that these have been recommended,4 existing technology
could allow access of the results and integrate all studies
using the agreed methodologies, accelerating the search for
answers.
While technology will facilitate research, it also can
enhance accessibility. Information should be available in
usable form, preferably integrated, graded and ranked, where
and when it is needed. This is far from the usual situation.
Information grows with profligate ease, knowledge slowly
and wisdom painfully.
Sometimes we suffer not from a scarcity of information but
from a surfeit. For the busy clinician, recommendations may
come packaged in a glut of guidelines more suitable for
specialized centers than the vast majority of settings where
1402 Stroke April 2007
stroke patients are seen. Recommendations need to be prior-
itized34 and their cost effectiveness evaluated.
The knowledge that we do have needs to be ranked much
more pragmatically and its application evaluated much more
systematically.
The Role of Journals
Medicine is not the only field bedeviled by too much spe-
cialized information and not enough creative synthesis. Over
a decade ago, the American Historical Review was seeking
articles that were new in content and interpretation and make
a fresh contribution to historical knowledge . . . . that reach
beyond the specialities that have enlivened yet also frag-
mented the discipline in recent years.35
Peer-reviewed journals play pivotal roles in evaluating,
publishing and publicizing knowledge. They may also en-
courage integration and interaction among different disci-
plines. An annual feature of the journal Stroke, Advances in
Stroke often carries articles coauthored by a clinician and a
basic scientist. Likewise, this was a noteworthy feature
introduced at the last Princeton Conference on Cerebrovas-
cular Diseases,36 where sessions were cochaired by a clinician
and a basic scientist and the relevant disciplines were pre-
sented and had their article discussed in the same session. The
proceedings of that conference were subsequently published
in Stroke.
Stroke offered a symposium on Cerebrovascular Disor-
ders: Opportunities for Transdisciplinary Progress at the
2007 International Stroke Conference, a theme likely to
continue in future conferences. The journal Stroke encourages
not only the acquisition, integration and application of knowl-
edge, but the evaluation of how this translates into the real
world.37 Stroke is the leading publication of articles in
outcomes research in the field and is appointing two section
editors to further promote this aspect.
Application of Knowledge
The more knowledge grows, the greater the gap between the
known and what is being applied. Several factors contribute
to this.
The emphasis of our research is on producing knowledge,
not in applying it. Many of the factors that influence patients
adherence to treatment regimes are beyond the scope of the
clinical approach and in competition with an environment
that promotes physical inactivity, over-consumption, and
unhealthy habits. We have too many guidelines but too few
guides. A more concentrated effort needs to occur among
government and organizations that deal with the different
diseases resulting from common vascular risk factors and a
better balance achieved between acute and chronic care and
prevention. Most healthcare systems are geared to recompense
costly, high-tech procedures. According to the Organization for
Economic Co-operation and Development (OECD), on average
most countries spend only around 3% of their health dollars in
prevention, the most cost-effective strategy of all (http://www.
oecd.org/document/11/0,2340,en_2649_33929_16502667_1_1_
1_1,00.html).
Novelty, marketing and techs appeal rather than cost-
effectiveness drive our healthcare systems. In the province of
Downloaded from stroke.ahajournals.org by on July 28, 2007
Ontario, Canada, the number of MRI units has become a
surrogate for quality of care, without any data on their
cost-effectiveness compared with other approaches or to less
expensive imaging modalities.
One way to assure that we get value for the money is that
all funding for activities related to stroke have a built-in
systematic requirement for evaluation. It will take effort and
resources to set up reliable mechanisms of evaluation, edu-
cation and dissemination. Whatever the price, it will be a
fraction of the daily, uncalculated costs of applying unsub-
stantiated opinions and unproven practices. Regretfully, that
represents most of what we do.
Almost certainly, whatever we do can be improved. The
only way to know whether we are improving is to evaluate
what we do. Research is not only an activity, it is an attitude.
Evaluation fosters the law of reciprocal enhancement: the
more we know, the more we can do, and the more we do, the
more we will know, and so on. Contributions can be made in
the most sophisticated laboratories and in the most modest of
stroke-care settings. Many people making small improve-
ments can have as much impact as a few people making big
advances. We need both.
Conclusion
Scientific and technological advances generate knowledge at
accelerating rates. The more knowledge grows, the greater
the gap between the known and its application.
We probably can improve both knowledge acquisition and
application by systematically integrating what we know and
evaluating what we do. This would apply to all aspects of
stroke and to all concerned.
There is no comparison between that which is lost by not
succeeding and that which is lost by not trying. Sir Francis
Bacon (15611626).
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