A of genius

With over 600 scholarly articles and 23,000 citations to his name, Professor Vladimir Hachinski has been at the forefront of stroke, sudden death and vascular cognitive impairment research for the last 40 years PROFESSOR VLADIMIR PROFESSOR HACHINSKI In reality, vascular disease does not involve the and grow after the occurrence of stroke. brain to such an extent, and when Similarly, inflammation is greater and flares. occurs it is often on the background of already Experimental treatment can suppress brain existing Alzheimer’s disease (AD). Thus, it is the changes and the cognitive consequences. co-occurrence and interaction of vascular disease and AD that is most commonly responsible for If we confirm this clinically, it will allow cognitive impairment in the elderly. Moreover, clinicians worldwide to use a joint the term vascular cognitive impairment can be treatment of anti-amyloid and anti- defined as any cognitive impairment caused by, or inflammatory agents to reduce the impact associated with, vascular factors. and mitigate the effects of stroke. It will also delay AD in those who might have This approach is promising as it emphasises become prone to it by the infarct. This has the one component that we can now treat and tremendous implications given that by the prevent, which is the vascular one. age of 73 around 50 per cent of the general population will have amyloid accumulations Another key area of your research is the within the brain. incidence of sudden death following stroke. Firstly, why does this occur, and secondly, why Our plans include a multidisciplinary attack are right-handed individuals more susceptible? on the problem. We are undertaking an Your earliest publication as a first- epidemiological study in collaboration with year resident in was on the The incidence of sudden death after stroke varies the Karolinska Institute in Stockholm and visual symptoms of . Why did according to the severity. The more severe the are collaborating with a number of centres you decide to have children draw their stroke, the more likely it is to happen. With that on both the clinical and experimental side. experience of migraine? said, it can also occur in individuals with mild stroke and those who are recovering from stroke. Finally, could you highlight your work on I decided to have the children draw their own stroke prevention? symptoms because a picture is worth a thousand As for the higher incidence for right-handed words. Since the experience was visual it made individuals, we are not entirely certain of the My colleague Dr Richard Chan and I lead a sense that they express it visually. Creating a reason. The likelihood is that in strongly right- Canada-wide study on stroke prevention. catalogue of different visual symptoms meant handed individuals the dominance of the right It is based on the premise that in order to that patients were able to point out which of the insula of the brain for sympathetic activities control blood pressure, weight reduction symptoms corresponded to their own experience. is probably greater than that in left-handers and other risk factors we need to change (and ambidextrous individuals), where the human behaviour. We believe that the most You were the first to coin the term ‘vascular dominance is more distributed between the powerful agent in accomplishing this is cognitive impairment’. Why was it important two insulas. Thus, if one insula is then damaged, another caring human being. to categorise certain cognitive disorders in the imbalance is much greater if sympathetic this way? function is largely one-sided. From this, we A preliminary study has shown that a have hypothesised that the origin of the fatal layperson working with the patient is often I suggested the term vascular cognitive arrhythmias is an imbalance between the a more effective strategy for reducing impairment because the expression ‘vascular sympathetic and parasympathetic systems. high blood pressure and body weight than dementia’ is seldom appropriate. In order to have the usual care provided by a doctor or one must have an inherited Your more recent research concerns AD and, nurse. The Canada-wide study will provide condition such as CADASIL (cerebral autosomal in particular, its relationship with stroke. definitive answers to the question and, if dominant arteriopathy with subcortical infarcts What are the implications of this study? positive, could lead to an effective, low- and leukoencephalopathy – the most common cost intervention that might be applied form of hereditary stroke disorder), or multiple We have shown experimentally that worldwide, helping to not only prevent cerebral infarcts that are extensive enough to compared to control animals amyloid stroke and cognitive deterioration, but heart involve several domains of cognition. deposits (a hallmark of AD) are larger attacks and renal failure.

110 INTERNATIONAL INNOVATION PROFESSOR VLADIMIR HACHINSKI

Understanding vascular mechanisms

The world of age-related is expanding and now, more than ever, there is a need for novel treatment, prevention and management strategies. Pioneering research undertaken in Canada and Sweden seeks to prevent stroke, delay Alzheimer’s disease and enhance brain health

ACCORDING TO THE World Heart Federation, An international leader, his career spans more location. This results in close interactions with 15 million people suffer stroke worldwide each than 40 years and his contributions to the all those concerned and leads to expertise being year. In the US alone, more than 140,000 fields of stroke, vascular cognitive impairments shared within the same environment”. people die annually from stroke. Not always and brain-heart interactions have seen him fatal, it is the second leading cause of serious indirectly save and improve millions of lives on a STROKE-RELATED RESEARCH long-term disability, after dementia. While the worldwide scale. incidence of stroke is declining in developed describes the changes observed in countries, largely due to efforts to reduce blood seen in the brain scans of elderly VASCULAR MECHANISMS pressure and smoking, the ageing population patients. These abnormalities are detected means that overall rates remain high. Indeed, Hachinski began his career researching more frequently among patients with studies show that the risk of stroke doubles for , publishing detailed descriptions and vascular dementia, and the term was coined each decade between the ages of 55 and 85. of the visual symptoms experienced by 100 by Hachinski in a 1986 paper to emphasise that children who were prone to the condition. At both the clinical relevance and pathogenesis A stroke is a sudden loss of brain function. It is the time, it was thought that migraine pain was of the condition were unknown at the time. caused by the interruption of flow of blood to caused by dilation of the brain’s blood vessels, The origins of the word are Greek, namely the the brain (ischaemic stroke) or the rupture of but Hachinski – along with Professor John W combination of leuko- (meaning ‘white’) and blood vessels in the brain (haemorrhagic stroke). Norris and Drs Perry Cooper and John Edmeads araios (meaning diminution of density). The The interruption of blood flow or the rupture of – demonstrated that pain could be relieved by many causes include small vessel infarcts in the blood vessels causes brain cells (neurons) in the ergotamine without changing the calibre of sub-cortical white matter. affected area to die. After a stroke, it is known the brain’s blood vessels. These findings led the that there is an increase in the production of migraine research community to refocus on the Following this work, Hachinski focused much the toxic amyloid beta (Aβ) peptides that are extracranial circulation. of his research on a phenomenon known as believed to cause Alzheimer’s disease. Certainly, cerebrogenic sudden death (CSD). Caused by neuroscientists are aware of the escalated risk Having studied the vascular mechanisms of fatal cardiac arrhythmias, it has long been of Alzheimer’s disease (AD) in people who have migraine, Hachinski turned his attention to the noted that stroke can lead to an increased risk had a stroke. treatment of stroke patients. Alarmed by the lack of developing CSD and this was something of emphasis on urgency, he introduced the term Hachinski and his fellow collaborators were Dr Vladimir Hachinski is Professor of Neurology ‘brain attack’. Now in common usage, the term keen to examine further. Indeed, the group – and , and Distinguished reflects the need to act swiftly, mobilising both which included Norris, and Drs Martin Myers, University Professor at Western University medical professionals and, more importantly, Gordon Froggat and Michael Sole – observed in Ontario, Canada. His primary objectives the general public. that some patients recovered from stroke only are to prevent stroke, delay AD and enhance to die suddenly for no apparent reason. brain health through integrated, synergetic, Moreover, his collaboration with Norris led population, experimental and clinical studies. to the establishment of the world’s first In an important study undertaken in 1992 with successful acute stroke unit in in the Drs David Cechetto and , 1970s and later in , Ontario. Their acute Hachinski identified the role of a specialised stroke units contain dedicated and specialised brain region, known as the insula, in stroke- healthcare workers that benefit the patients induced cardiovascular disturbances. These on multiple levels and ultimately save lives, as disturbances included electrocardiographic Hachinski explains: “The key to stroke units is changes, a known arrhythmia associated with concentrating stroke patients in one physical CSD. This breakthrough study has meant that the efforts of researchers in the field who are examining post-infarction CSD have now

WWW.RESEARCHMEDIA.EU 111 INTELLIGENCE POPULATION, CLINICAL AND EXPERIMENTAL STUDIES IN THE PREVENTION AND DELAY OF STROKE AND The key to successful stroke units is ALZHEIMER’S DISEASE concentrating stroke patients in one OBJECTIVES physical location To prevent stroke, delay Alzheimer’s disease and enhance brain health through integrated, synergetic, population, experimental and clinical studies. KEY COLLABORATORS Western University, Canada: Dr David Cechetto; Dr Daniel Hackam; Dr Manuel Montero Odasso; Dr Anne Snowdon; Dr Shawn Whitehead , Canada: Dr Moira Kapral Karolinska Institute, Sweden: Dr Miia Kivipelto McGill University, Canada: Dr Alexander Thiel shifted from the the brain stem to the insula hypothesised that these mechanisms might FUNDING and amygdala. play a meditative role between AD and stroke.

Premier’s Discovery Award in The Life Sciences The team used a rat model of cerebral STROKE-RELATED DEMENTIA and Medicine for ‘groundbreaking research on ischaemia, along with histochemical and the relationship between stroke and Alzheimer’s Approximately 30 per cent of stroke patients immunohistochemical analyses which disease’ • Canadian Institutes of Health Research meet the diagnostic criteria for dementia are employed to examine the chemical CONTACT three months after infarction. In light of composition of the cells and tissues. Hachinski this, Hachinski is now focusing much of his and his colleagues demonstrated that there Professor Vladimir Hachinski, MD DSc work on these interactions between stroke was an enhanced inflammatory response in Western University and dementia. An imprint that he has left animals with amyloid-beta (a component London Health Sciences Centre on this specific field of research is one that of AD ) toxicity and ischaemia. Department of CNS bears his own name: the Hachinski Ischemic This critical finding holds much promise in 339 Windermere Road Score (HIS). This commonly used tool allows a clinical setting as an anti-inflammatory London, Ontario, Canada clinicians to differentiate vascular dementia and anti-amyloid treatment that might N6A 5A5 from neurodegenerative forms. Vascular mitigate deficits associated with this deadly dementia is the second most common form combination of pathologies. T +1 519 663 3624 of dementia after AD, and is caused by F +1 519 663 3910 problems in the supply of blood to the brain. AN EXEMPLAR E [email protected] The HIS is important because it means that healthcare specialists are able to identify the These are just a few examples of Hachinski’s www.youtube.com/watch?v=e_Tnau55AGs vascular components of cognitive impairment, studies that have made substantial www.chrcrm.org/en/rotm/dr-vladimir- which are highly treatable compared to their contributions to the field of vascular hachinski-cm-md-frcpc-dsc degenerative counterparts. research and associated pathologies. Over the course of his career, his work on vascular PROFESSOR VLADIMIR HACHINSKI is a Interestingly, Hachinski first developed the HIS cognitive impairment, stroke and brain-heart Distinguished Professor and past Richard and for different reasons: “I developed it in order to interactions has helped to delay or avoid Beryl Ivey Chair of the Department of Clinical define patients that I was studying for cerebral cerebral vascular disease. Neurological Sciences at Western University, blood flow investigations,” he reflects: “It turns Canada. Together with Professor John W Norris, out that these sophisticated studies are hardly Further to this, Hachinski’s collaborative research he established the world’s first successful acute ever quoted and it was the very simple way of has changed the way the public and clinicians stroke unit. He also discovered, in collaboration identifying the vascular component of cognitive approach stroke. It is now understood that swift impairment that has really taken off”. action must be taken at the onset of stroke with Dr David Cechetto, the brain’s insula role symptoms to prevent serious damage, and this in sudden death and a link between Alzheimer’s With AD being the most common form of urgency has been widely publicised in public disease and stroke, paving the way for new dementia, and stroke affecting so many people health initiatives. Similarly, Hachinski’s studies treatments. Hachinski is the first Canadian worldwide, studies into the interactions into age-related diseases and their interactions President of the World Federation of Neurology, between stroke and AD are suprisingly rare. have focused almost entirely on vascular the Founding Chair of the Working Group, World Epidemiological research by Hachinski and components and it is these components that are Brain Alliance, and a recipient of the Order of others have found that these two pathologies treatable and preventable. Canada. Formerly, he was also the Editor-in-Chief occur together and pose reciprocal risks. of the journal Stroke, the leading publication in In 2005, Hachinski, in collaboration with The steady shift in demographics in the last the field. Drs Shawn Whitehead and David Cechetto, few decades now means that humans are living presented an attractive, synergistic theory for longer than ever before. Thus, understanding this using a rat model of cerebral ischemia. It is and preventing pathologies associated with well known that inflammatory mechanisms are ageing is becoming more relevant for healthcare involved in AD pathology and the investigators services and individuals alike. 112 INTERNATIONAL INNOVATION