Stroke and Vascular Cognitive Impairment: A Transdisciplinary, Translational and Transactional Approach

University of Western Ontario, London, Ontario, Canada.
Stroke (Impact Factor: 5.72). 05/2007; 38(4):1396. DOI: 10.1161/01.STR.0000260101.08944.e9
Source: PubMed


Advances 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 one's work is so exalted that it cannot be improved, nor so humble that it has no value. We can all make a difference.

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    • "Cognitive impairment was proposed as a prognostic index of stroke by the Hachinski group in 2007 [5]. Subclinical stroke and leukodystrophy may cause some cognitive changes in older patients, such as disturbances of thinking and reasoning, disturbances of memory and recall of recent events, and disorders of social behavior and depression [6,7]. "
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    ABSTRACT: Background Stroke is the second most common cause of mortality and the leading cause of neurological disability, cognitive impairment and dementia worldwide. Nimodipine is a dihydropyridinic calcium antagonist with a role in neuroprotection, making it a promising therapy for vascular cognitive impairment and dementia. Methods/design The NICE study is a multicenter, randomized, double-blind, placebo-controlled study being carried out in 23 centers in China. The study population includes patients aged 30–80 who have suffered an ischemic stroke (≤7 days). Participants are randomly allocated to nimodipine (90 mg/d) or placebo (90 mg/d). The primary efficacy is to evaluate the level of mild cognitive impairment following treatment of an ischemic stroke with nimodipine or placebo for 6 months. Safety is being assessed by observing side effects of nimodipine. Assuming a relative risk reduction of 22%, at least 656 patients are required in this study to obtain statistical power of 90%. The first patient was recruited in November 2010. Discussion Previous studies suggested that nimodipine could improve cognitive function in vascular dementia and Alzheimer’s disease dementia. It is unclear that at which time-point intervention with nimodipine should occur. Therefore, the NICE study is designed to evaluate the benefits and safety of nimodipine, which was adminstered within seven days, in preventing/treating mild cognitive impairment following ischemic stroke.
    BMC Neurology 09/2012; 12(1):88. DOI:10.1186/1471-2377-12-88 · 2.04 Impact Factor
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    • "It is being increasingly recognized that the prevalence of vascular cognitive impairment (VCI) is higher than originally thought. Since VCI is considered to develop under the influence of various cardiovascular risk factors, it is emerging as a potentially treatable and preventable form of dementing disorders.1 However, currently available therapeutic options for treatment of dementia, such as cholinesterase inhibitors, were originally devised for Alzheimer's disease (AD), and their application in vascular dementia (VaD) has produced limited and uncertain clinical benefit.2 "
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    ABSTRACT: It was recently reported that the prevalence of poststroke memory dysfunction might be higher than previously thought. Stroke may exist concomitantly with underlying Alzheimer's disease (AD), and so we determined whether post-stroke memory dysfunction indicates manifestation of underlying subclinical AD. Of 1201 patients in a prospective cognitive assessment database, we enrolled subjects with poststroke amnestic vascular cognitive impairment-no dementia (aVCIND; n=48), poststroke nonamnestic vascular cognitive impairment-no dementia (naVCIND; n=50), and nonstroke amnestic mild cognitive impairment (aMCI; n=65). All subjects had cognitive deficits, but did not meet the criteria for dementia. A standardized neuropsychological test battery and magnetic resonance imaging were performed at least 90 days after the index stroke (mean, 473 days). Visual assessment of medial temporal atrophy (MTA) was used as a measure of underlying AD pathology. The MTA score was significantly lower in the naVCIND group (0.64±0.85, mean±SD) than in the aVCIND (1.10±1.08) and aMCI (1.45±1.13; p<0.01) groups. Multivariable ordinal logistic regression analysis revealed that compared with naVCIND, aVCIND [odds ratio (OR)=2.69; 95% confidence interval (CI)=1.21-5.99] and aMCI (OR=5.20; 95% CI=2.41-11.23) were significantly associated with increasing severity of MTA. Our findings show that compared with poststroke naVCIND, the odds of having more-severe MTA were increased for poststroke aVCIND and nonstroke aMCI.
    Journal of Clinical Neurology 03/2012; 8(1):43-50. DOI:10.3988/jcn.2012.8.1.43 · 1.70 Impact Factor
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    • "The clinical variability of stroke, mainly in terms of duration, localization and severity of ischemia, as well as the patients’ age and coexisting systemic diseases, poses huge challenges for clinical research, as very large patient groups are needed to avoid the confounding effects of disease diversity. Although experimental longitudinal clinical studies are of major importance for understanding stroke, having provided strong evidence for the existence of genetic and environmental influence factors, they are seldom helpful in understanding disease mechanisms and their results can be misleading [4]. On the other hand, in vitro systems alone cannot thoroughly evaluate stroke and its consequences, given the importance of the brain vasculature to study the effects of abnormal brain perfusion and given the involvement of other systems as well [5]. "
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    ABSTRACT: Ischemic stroke is one of the leading causes of long-term disability and death in developed and developing countries. As emerging disease, stroke related mortality and morbidity is going to step up in the next decades. This is both due to the poor identification of risk factors and persistence of unhealthy habits, as well as to the aging of the population. To counteract the estimated increase in stroke incidence, it is of primary importance to identify risk factors, study their effects, to promote primary and secondary prevention, and to extend the therapeutic repertoire that is currently limited to the very first hours after stroke. While epidemiologic studies in the human population are essential to identify emerging risk factors, adequate animal models represent a fundamental tool to dissect stroke risk factors to their molecular mechanism and to find efficacious therapeutic strategies for this complex multi- factorial disorder. The present review is organized into two parts: the first part deals with the animal models that have been developed to study stroke and its related risk factors and the second part analyzes the specific stroke models. These models represent an indispensable tool to investigate the mechanisms of cerebral injury and to develop novel therapies.
    The Open Neurology Journal 06/2010; 4(2):26-33. DOI:10.2174/1874205X01004020026
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