Vladimir Hachinski

Vladimir Hachinski
CM OOnt FRCPC FRSC
Personal details
BornZhytomyr, Ukrainian Soviet Socialist Republic, USSR
OccupationNeuroscientist

Vladimir Hachinski is a Canadian clinical neuroscientist and researcher based at the Schulich School of Medicine and Dentistry at Western University.[1] He is also a Senior Scientist at London's Robarts Research Institute.[2] His research pertains in the greatest part to stroke and dementia, the interactions between them and their joint prevention through holistic brain health promotion.[3] He and John W. Norris helped to establish the world's first successful stroke unit at Sunnybrook Hospital in Toronto,[4][5] and, by extension, helped cement stroke units as the standard of care for stroke patients everywhere.[6][7] He discovered that the control of the heart by the brain is asymmetric, the fight/flight (sympathetic) response being controlled by the right hemisphere and the rest and digest (parasympathetic) response being controlled by the left hemisphere and damage to one key component (the insula) can lead to heart irregularities and sudden death. This discovery has added fundamental knowledge to how the brain controls the heart and blood pressure and lays the foundation for helping prevent sudden death.[8]

Hachinski has held many prominent positions in the global neurology community, including editor-in-chief of the journal Stroke the leading publication in the field and president of the World Federation of Neurology and founder of World Brain Alliance. He is a Fellow of the Royal Society of Canada (FRSC) and the Canadian Academy of Health Sciences (FCAHS), a Member of the Orders of Ontario and Canada, and the recipient of several national and international awards and recognitions for his research and advocacy.

Early life, education, and early career

Hachinski was born in Zhytomyr, Ukraine, the eldest of three children. He moved with his family to Caripito, Venezuela as a child. The family moved to Port Perry, Ontario, Canada thereafter. He graduated from Port Perry High School a year later at the top of his class .[9]

Hachinski received his MD in 1966 from the University of Toronto,[10][11] and completed his residency in internal medicine and neurology in Toronto and Montreal, followed by a neurophysiology fellowship in Toronto. He received his formal accreditation in neurology as a Fellow of the Royal College of Physicians and Surgeons of Canada (FRCPC) in 1972.[10] From 1973-74, a research fellowship with the Ontario Department of Health brought him to a cerebrovascular laboratory at the National Hospital for Nervous Diseases in London, England, and then to the Department of Clinical Physiology at Bispebjerg Hospital in Copenhagen, Denmark.[9]

Following this, he returned to Toronto to take a staff position in the Department of Neurosciences at Sunnybrook Medical Centre, where he and Dr. John W. Norris established the MacLachlan Stroke Unit, Canada's first acute stroke unit.[4][11] Hachinski remained at Sunnybrook until 1980, when he moved to London, Ontario to act as a neurology consultant for its major health centres: University Hospital, Victoria Hospital, St. Joseph's Hospital, and the London Psychiatric Hospital. He was hired concurrently as a professor at Western University (then called the University of Western Ontario).[10] During this time (and until 1990), he also acted as Director of the Investigative Stroke Unit at London's University Hospital.

In 1987, he earned a Master of Science degree from McMaster University in Hamilton, Ontario, studying in the Department of Epidemiology and Biostatistics with a focus on design, measurement, and evaluation. The University of London’s highest earned degree, Doctor of Science (in Hachinski's case, in medicine), was conferred upon him in 1988 for his “contributions to migraine, stroke, and dementia.”[10]

Research

Vascular cognitive impairment

At the beginning of Hachinski's career, the view prevailed that most dementias were caused by hardened brain arteries (mental deterioration via cerebral atherosclerosis). Hachinski showed in 1975 that, in fact, only a small minority of dementias were so-caused, and that most were “multi-infarct dementias” — dementias caused by multiple, small, often imperceptible strokes.[12] The terms “vascular dementia” and “vascular cognitive impairment” would later be widely adopted to describe all cognitive impairments "with a vascular component" in order to distinguish them from primary degenerative dementia (i.e., Alzheimer disease and senile dementia) and to emphasize that they are preventable and treatable, insofar as their vascular causes (i.e., atherosclerosis, stroke, etc.) are treatable as well.[13] He has offered an explanation for the origin of some of these lesions and associated symptoms through his concept of ambibaric brain.  He postulates that the brain has two complementary blood pressure systems, one high and one low and disturbances in each lead to different types of preventable lesions.[14]

At the time, the prevalent view that dementia ensued from the slow strangulation of the brain's blood supply by hardening of the arteries spawned a whole industry of brain vessel “vasodilators”. He showed that brain blood vessels in dementia were not “hardened” and that “vasodilators” were not only expensive but useless. He also developed an eponymic “ischemic score” that continues to be widely used to identify the vascular (treatable and preventable) component of dementia.[15] Successfully distinguishing between the two is tremendously important for patient prognosis, as treating the vascular causes of dementias can mitigate their effects. The scale is a prolifically cited tool, and has since been validated and optimized for use outside of clinical research settings.[16]

In 1986, the journal, Archives of Neurology published a series of papers by Hachinski, Harold Merskey and colleagues on the rarefaction of white matter in the brains of elderly people. These papers were among the first to recognize the importance of white matter lesions as risks for stroke and dementia. Rarefaction of white matter in the brain had already been shown to be correlated with a wide variety of health problems, but these papers were groundbreaking for two reasons especially: First, they introduced the term, “leukoaraiosis,” a word derived by Hachinski, Paul Potter and Harold Merskey to etymologically and Hippocratically describe the rarefaction; and second, they specifically highlighted a previously underappreciated relationship between vascular risk factors for cognitive impairment (i.e., treatable and preventable risk factors for both stroke and multi-infarct dementia) and leukoaraiosis. By coining “leukoaraiosis,” Hachinski drew medical practitioners’ attention to these white matter hypodensities in the brains of patients affected by small strokes.[17][18][19]

Hachinski continued to develop and promote his novel approach to dementia — viewing it as a product of preventable and treatable vascular problems, thus itself also amenable to prevention, delay, and mitigation — eventually coining it as the “vascular cognitive impairment approach” to dementias in 1994.[20][21] This proactive and preventative, rather than solely retroactive and treatment-based approach included other novel coinages, such as “brain at risk,” describing patients without cognitive impairment but with risk factors for it.[22][23][24]

Even with these developments, available diagnostic criteria for dementias continued to present a challenge, as they were not able to capture the complex, interactive, and adaptive nature of brain pathologies leading to dementia. For this reason, in 2006, Hachinski decided to lead (with Gabrielle LeBlanc) the development of core common standards to describe the clinical, neuropsychological, imaging, genetic, and neuropathological features of cognitive impairment. This standardization has allowed for ongoing improvement of the diagnostic criteria with new knowledge, comparison of results from different studies, and analysis & meta-analysis using “big data” techniques.[25]

Acute stroke

The MacLachlan Stroke Unit at Sunnybrook, Canada's first stroke unit (est. 1975), was almost 20 years ahead of its time; stroke units have been considered the most effective treatment for stroke patients of all ages, severities, and types only since the 1990s.[26][27] Hachinski and Norris' early work with that unit and others helped to cement the importance of dedicated wards for stroke patient monitoring and treatment, but his research over the next 17 years also shaped how those treatments and monitoring methods are executed.

In 1986, while he was Director of the Investigative Stroke Unit at University Hospital in London, he developed (with Robert Coté), the Canadian Neurological Scale – a simple but systematic tool, usable by non-physicians for evaluating and monitoring the neurological status of patients with acute stroke.[28] Later, in 1992, he (with collaborators David Cechetto and Stephen Oppenheimer) began work to explore possible mechanisms for observed increases in catecholamines, cardiac enzymes, arrhythmias, and sudden death following acute stroke. This would eventually lead to the discovery that the insula of the brain is the mediator of these various cardiac complications.[3][29][30][31][32] Knowing this alters doctors to monitor the heart closely, to prevent sudden death.

The scientific bases for preventing stroke and dementia together have been summarized by an international panel of experts.[33][34]

Since stroke, heart disease and dementia represent risks for each other and share the same risk and protective factors, he advocates preventing this “Triple Threat” together.[35]

He leads a multidisciplinary team studying for the first time together environmental, socioeconomic and individual risk and protective factors in the joint prevention of stroke, heart disease and dementia.

He is a participant in an initiative to make brain health the top priority.  He has offered a definition of brain health based on the World Health Organization definition of health” “A state of complete physical, mental and social well-being through a full, balanced, continuous development and exercise of the brain[36] or in lay terms "Brain health is when thinking, feeling and connecting are the best that they can be in a sage, healthy environment."

Stroke prevention

In addition to his interest in the mechanisms of stroke and best practices for treatment, Hachinski also has a keen research interest in stroke prevention. He acted as the principal neurological investigator on several seminal, multicentre studies, beginning with the Canadian-American Ticlopidine study (1983–88)[37][38] and the Extracranial/Intracranial Arterial Bypass Surgery trial (1983–87). The former showed a preventative advantage to the drug Ticlopidine over commonly-prescribed Aspirin, while the latter showed that the increasingly popular and very expensive EC/IC arterial bypass procedure did not significantly reduce the risk of ischemic stroke.[39]

In 2003, alongside several other researchers, Hachinski began a proof of principle study through the Canadian Stroke Network on secondary stroke prevention. The study aimed to explore the efficacy of stroke risk-factor counselling and monitoring in effecting lifestyle changes and prescription adherence in patients, as well as exploring barriers and testing possible solutions to effective stroke risk-factor management.[40] The preliminary results were extremely promising, showing that the addition of non-medical personnel to usual stroke care results in far better outcomes and reduced risk-factors. That initial study led to the creation of a multi-centre study in 2009 under the direction of Richard Chan.[41]

Population health

Hachinski's home province of Ontario, Canada introduced a formal Provincial Stroke System in 2000.[42] Hachinski advocates a strategy of preventing some dementias through the prevention of stroke.[43] With his colleagues, he showed, for the first time, a concomitant decrease in the incidence of stroke and dementia at a whole-population level.[44] He is leading a team from 5 Western University faculties, 5 provinces and 4 countries, to find out how and help apply the lessons widely.

He advocates and will help implement a new approach to the joint prevention of stroke, ischemic heart disease and dementia (the terrible three).

The new approach is based on these premises:

1. The “terrible three” inflict the highest number of death and disability adjusted life years (DALY’s) globally. However, they share the same treatable and preventable risk factors and represent risks for each other. Consequently, conditions that occur together should be prevented together.

2. To be effective prevention has to occur in “actionable units” small enough that their members have or can develop a sense of community.

3. The approach has to be:

  a. Comprehensive – meaning that all relevant factors need to be considered: Environment, socio-economic factors and individual risk and protective factors

  b. Customized – to address the main and manageable problems

  c. Cost-effective – to justify why it should be done ahead of other priorities

This approach is known as the CCCAP or the 3C’s approach.[45]

Additionally, he advocates a change in strategy. Instead of using fear, warning people that if they don’t lead a healthy lifestyle they will suffer a stroke, heart disease or dementia decades later, the aim is to achieve brain/mental health now.[46]

Key administrative positions and advocacy

  • 2015 led the development of a Proclamation about the joint prevention of stroke and dementia, endorsed by all the major international organizations dealing with both.[47] Since then leading the effort to implement the Proclamation on behalf of the World Stroke Organization.
  • 2011–2013: Founding chair, World Brain Alliance, a collection of international organizations promoting brain/mental health and reducing brain/mental health disorders,[3][48][49] founded on three premises:[50]
    1. There is no health without brain health
    2. Brain health begins with the mother's and the child's education
    3. Our brains are our future
    4. Knowledge accrues in pieces but is understood in patterns
    5. God may forgive our sins, but our bodies hold grudges
    6. We need fewer watch dogs and more hunting dogs
    7. We need not only rising stars, but North Stars
  • 2010-13 : President, World Federation of Neurology (WFN; international body representing world neurology); first Canadian in its six decades history[3][51]
  • 2006-10: Vice President (North America), WFN[52]
  • 2000-10: Editor-in-Chief, Stroke[3][11] He introduced 9 international editions and a mentorship program for authors from developing countries.
  • 2008-12 : Vice President, World Stroke Organization[3][53]
  • 2004-06: Led working group to develop World Stroke Agenda (2004, Vancouver) and World Stroke Day Proclamation (2006, Cape Town), observed every October 29.[54][55]

Non-scientific publications

Hachinski's primary popular medicine contributions have been publications in cooperation with his son, Vladimir, and daughter, Larissa. With Vladimir, he published an article in the Journal of the Canadian Medical Association called, "Music and the Brain" in August 1994.[56] With Larissa, he published the book, Stroke: A Comprehensive Guide to Brain Attack in 2003. Coining and employing the term “brain attack,” the book was written to increase public awareness of the importance of adequate stroke care and early intervention.[3][11][57]

Medical historical

An interest in the history of medicine has led Hachinski to publish several articles on the subject over the course of his career:

  • Hachinski, V (March 1999). "Stalin's last years: delusions or dementia?". European Journal of Neurology. 6 (2): 129–132. doi:10.1111/j.1468-1331.1999.tb00004.x. PMID 10053223. S2CID 44833937.
  • Hachinski, Vladimir (1997). "Kos (A poem about Hippocrates)". The Lancet. 349 (9064): 1561. doi:10.1016/S0140-6736(05)62150-2. S2CID 208790603.
  • Gasecki, Andrew P.; Hachinski, Vladimir (1996). "On the names of Babinski". Canadian Journal of Neurological Sciences. 23 (1): 76–79. doi:10.1017/s0317167100039226. PMID 8673967.
  • Hachinski, Vladimir (1993). "Neurology in Islamic Spain: a call for further research". Journal of the History of the Neurosciences. 2 (1): 45–51. doi:10.1080/09647049309525551. PMID 11618443.
  • "Cajal: crossroads to greatness". Annals of the Royal College of Physicians and Surgeons of Canada. 25: 290–292. 1992.
  • Hachinski, Vladimir (1986). "H.J.M Barnett: a biographical sketch". Surgical Neurology. 26 (6): 529–531. doi:10.1016/0090-3019(86)90334-4. PMID 3535140.
  • "H.J.M Barnett: a biographical sketch." "Modern Neurosurgical Giants" Ed: Bucy PC. Elsevier, New York, pp. 35–38, 1986.
  • "Transient cerebral ischemia: a historical sketch." In: Historical Aspects of the Neurosciences. (Eds) Rose FC, Bynum WF. Raven Press, New York, pp. 185–193, 1982.

Arts and humanities

He possesses an honours degree in history from the University of London, UK, is a Corresponding Member of the North American Academy of the Spanish Language (a corresponding academy of the Royal Spanish Academy)[58] and has published a poetry anthology, Resonancias,[59] in Spanish under the pen name Alejandro Aranda.[11] In addition, "Dream Waltz," composed by Hachinski and orchestrated by Jason Stanford (Professor of Theory and Composition at Western University), premiered at the Musikverein in Vienna, Austria by the Brno Philharmoniker on September 24, 2013.[60][61]

Honours and recognition

Awards/recognitions

Over the course of his career, Hachinski has been the recipient of many awards and recognitions in his field. The most notable and significant are outlined below.

Honorary degrees

Hachinski holds four honorary doctorates. The first, Doctor of Medicine honoris causa from the University of Salamanca, Spain (the oldest university of the Spanish speaking world) was awarded in 2000.[79] This was followed by Doctor of the University honoris causa from the University of Buenos Aires, Argentina (2005),[80][81] Doctor of Medicine honoris causa from the University of Cordoba, Argentina (2007),[82] and Doctor honoris causa from the Russian Academy of Medical Sciences (2012).[3][83]

References

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  2. ^ "Vladimir Hachinski, CM, MD, DSc, FRCPC, Doctor honoris causaX4". www.robarts.ca. Retrieved 2022-08-16.
  3. ^ a b c d e f g h i j "Department of Clinical Neurological Sciences at Western University - Vladimir Hachinski Faculty Profile". www.cnsuwo.ca. Retrieved 2016-05-31.
  4. ^ a b "Order of Canada Citation". Retrieved 2016-05-31.
  5. ^ "A stroke of genius" (PDF). Dementia Action Alliance. researchmedia.eu. Retrieved 2016-06-13.
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  7. ^ Langhorne, Peter; Ramachandra, Samantha; Stroke Unit Trialists' Collaboration (23 April 2020). "Organised inpatient (stroke unit) care for stroke: network meta-analysis". The Cochrane Database of Systematic Reviews. 4 (4): CD000197. doi:10.1002/14651858.CD000197.pub4. ISSN 1469-493X. PMC 7197653. PMID 32324916.
  8. ^ Sörös P, Hachinski V (2012). "Cardiovascular and neurological causes of sudden death after ischaemic stroke". Lancet Neurol. 11 (2): 179–88. doi:10.1016/S1474-4422(11)70291-5. PMID 22265213. S2CID 661118.
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  12. ^ Hachinski, VC; Lassen, NA; Marshall, J (27 July 1974). "Multi-infarct dementia. A cause of mental deterioration in the elderly". Lancet. 2 (7874): 207–10. doi:10.1016/s0140-6736(74)91496-2. PMID 4135618.
  13. ^ Alagiakrishnan, Kannayiram; Memon, Mohammed A. "Vascular Dementia". MedScape. Background. Retrieved 2016-05-31.
  14. ^ Hachinski, Vladimir; Østergaard, Leif (June 2021). "The Ambibaric Brain: Pathophysiological and Clinical Implications". Stroke. 52 (6): e259–e262. doi:10.1161/STROKEAHA.120.033492. PMID 33940956. S2CID 233719602.
  15. ^ Hachinski, V. C.; Iliff, L. D.; Zilhka, E.; Du Boulay, G. H.; McAllister, V. L.; Marshall, J.; Russell, R. W. R.; Symon, L. (1 September 1975). "Cerebral Blood Flow in Dementia". Archives of Neurology. 32 (9): 632–637. doi:10.1001/archneur.1975.00490510088009. PMID 1164215.
  16. ^ Hachinski, Vladimir; Oveisgharan, S; Romney, AK; Shankle, WR (1 February 2012). "Optimizing the Hachinski Ischemic Scale". Archives of Neurology. 69 (2): 169–75. doi:10.1001/archneurol.2011.1698. PMID 21987392.
  17. ^ Steingart, A.; Hachinski, V. C.; Lau, C.; Fox, A. J.; Diaz, F.; Cape, R.; Lee, D.; Inzitari, D.; Merskey, H. (1 January 1987). "Cognitive and Neurologic Findings in Subjects With Diffuse White Matter Lucencies on Computed Tomographic Scan (Leuko-Araiosis)". Archives of Neurology. 44 (1): 32–35. doi:10.1001/archneur.1987.00520130024012. PMID 3800719.
  18. ^ Aminoff, Michael Jeffrey (2008-01-01). Neurology and General Medicine. Elsevier Health Sciences. p. 128. ISBN 978-0443067075.
  19. ^ Hachinski, V. C.; Potter, P.; Merskey, H. (1 January 1987). "Leuko-Araiosis". Archives of Neurology. 44 (1): 21–23. doi:10.1001/archneur.1987.00520130013009. PMID 3800716.
  20. ^ Hachinski, Vladimir (1994). "Vascular Dementia: A Radical Redefinition". Dementia and Geriatric Cognitive Disorders. 5 (3–4): 130–132. doi:10.1159/000106709. PMID 8087166.
  21. ^ Bowler, JV; Hachinski, V (August 1995). "Vascular cognitive impairment: a new approach to vascular dementia". Baillière's Clinical Neurology. 4 (2): 357–76. PMID 7496625.
  22. ^ Cappa, S. F. (2008). Cognitive Neurology: A Clinical Textbook. Oxford University Press. p. 258. ISBN 9780198569275.
  23. ^ Hachinski, V (12 September 1992). "Preventable senility: a call for action against the vascular dementias". Lancet. 340 (8820): 645–8. doi:10.1016/0140-6736(92)92177-h. PMID 1355217. S2CID 30957302.
  24. ^ Hachinski, V. C.; Bowler, J. V.; Loeb, C. (1 October 1993). "Vascular dementia". Neurology. 43 (10): 2159–60, author reply 2160–1. doi:10.1212/wnl.43.10.2159-a. PMID 8414002. S2CID 40803369.
  25. ^ Hachinski, Vladimir; Iadecola, Costantino; Petersen, Ron C.; Breteler, Monique M.; Nyenhuis, David L.; Black, Sandra E.; Powers, William J.; DeCarli, Charles; Merino, Jose G.; Kalaria, Raj N.; Vinters, Harry V.; Holtzman, David M.; Rosenberg, Gary A.; Wallin, Anders; Dichgans, Martin; Marler, John R.; Leblanc, Gabrielle G. (September 2006). "National Institute of Neurological Disorders and Stroke–Canadian Stroke Network Vascular Cognitive Impairment Harmonization Standards". Stroke. 37 (9): 2220–2241. doi:10.1161/01.STR.0000237236.88823.47. PMID 16917086. S2CID 10272849.
  26. ^ Langhorne, P.; Williams, B.O.; Gilchrist, W.; Howie, K. (August 1993). "Do stroke units save lives?". The Lancet. 342 (8868): 395–398. doi:10.1016/0140-6736(93)92813-9. PMID 8101901. S2CID 1756294.
  27. ^ Sinha, S.; Warburton, E.A. (September 2000). "The evolution of stroke units—towards a more intensive approach?". QJM. 93 (9): 633–638. doi:10.1093/qjmed/93.9.633. PMID 10984558.
  28. ^ Côté, R; Hachinski, V C; Shurvell, B L; Norris, J W; Wolfson, C (July 1986). "The Canadian Neurological Scale: a preliminary study in acute stroke". Stroke. 17 (4): 731–737. doi:10.1161/01.str.17.4.731. PMID 3738958.
  29. ^ Oppenheimer, SM; Hachinski, VC (February 1992). "The cardiac consequences of stroke". Neurologic Clinics. 10 (1): 167–76. doi:10.1016/S0733-8619(18)30239-1. PMID 1557001.
  30. ^ Oppenheimer, Stephen M.; Cechetto, DF; Hachinski, VC (1 May 1990). "Cerebrogenic Cardiac Arrhythmias". Archives of Neurology. 47 (5): 513–9. doi:10.1001/archneur.1990.00530050029008. PMID 2185720.
  31. ^ Oppenheimer, S. M.; Gelb, A.; Girvin, J. P.; Hachinski, V. C. (1 September 1992). "Cardiovascular effects of human insular cortex stimulation". Neurology. 42 (9): 1727–32. doi:10.1212/wnl.42.9.1727. PMID 1513461. S2CID 32371468.
  32. ^ "A stroke of genius" (PDF). Understanding vascular mechanisms > Stroke Related Research > par. 3. Retrieved 2016-05-31.
  33. ^ Hachinski, Vladimir; Einhäupl, Karl; Ganten, Detlev; Alladi, Suvarna; Brayne, Carol; Stephan, Blossom C. M.; Sweeney, Melanie D.; Zlokovic, Berislav; Iturria-Medina, Yasser; Iadecola, Costantino; Nishimura, Nozomi; Schaffer, Chris B.; Whitehead, Shawn N.; Black, Sandra E.; Østergaard, Leif (2019-09-22). "Special topic section: linkages among cerebrovascular, cardiovascular, and cognitive disorders: Preventing dementia by preventing stroke: The Berlin Manifesto". International Journal of Stroke: 174749301987191. doi:10.1177/1747493019871915. ISSN 1747-4930. PMID 31543058. S2CID 202732274.
  34. ^ Hachinski, Vladimir; Ganten, Detlev; Lackland, Daniel; Kreutz, Reinhold; Tsioufis, Konstantinos; Hacke, Werner (2018-10-17). "Implementing the Proclamation of Stroke and Potentially Preventable Dementias". International Journal of Stroke. 13 (8): 780–786. doi:10.1177/1747493018799965. ISSN 1747-4930. PMID 30328803. S2CID 53528721.
  35. ^ Hachinski, Vladimir (2021-08-10). "Brain Health—Curbing Stroke, Heart Disease, and Dementia: The 2020 Wartenberg Lecture". Neurology. 97 (6): 273–279. doi:10.1212/WNL.0000000000012103. ISSN 0028-3878. PMID 33883239. S2CID 233349756.
  36. ^ Hachinski, Vladimir; Avan, Abolfazl; Gilliland, Jason; Oveisgharan, Shahram (May 2021). "A new definition of brain health". The Lancet Neurology. 20 (5): 335–336. doi:10.1016/s1474-4422(21)00102-2. ISSN 1474-4422. PMID 33894188. S2CID 233328835.
  37. ^ Gent, M; Blakely, J A; Easton, J D; Ellis, D J; Hachinski, V C; Harbison, J W; Panak, E; Roberts, R S; Sicurella, J; Turpie, A G (October 1988). "The Canadian American Ticlopidine Study (CATS) in thromboembolic stroke. Design, organization, and baseline results". Stroke. 19 (10): 1203–1210. doi:10.1161/01.str.19.10.1203. PMID 3051529.
  38. ^ Gent, Michael; Donald Easton, J.; Hachinski, VladimirC.; Panak, Edouard; Sicurella, Jane; Blakely, JohnA.; Ellis, DavidJ.; Harbison, JohnW.; Roberts, RobinS.; Turpie, AlexanderG.G. (June 1989). "The Canadian American Ticlopidine Study (Cats) in Thromboembolic Stroke". The Lancet. 333 (8649): 1215–1220. doi:10.1016/s0140-6736(89)92327-1. PMID 2566778. S2CID 22484643.
  39. ^ EC/IC Bypass Study, Group. (7 November 1985). "Failure of Extracranial–Intracranial Arterial Bypass to Reduce the Risk of Ischemic Stroke". New England Journal of Medicine. 313 (19): 1191–1200. doi:10.1056/NEJM198511073131904. PMID 2865674.
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  41. ^ Chan, Richard. "Promoting Adherence to a Regimen of risk factor modification by Trained Non-medical personnel Evaluated against Regular practice Study". International Standard Randomised Controlled Trial Number (ISRCTN) Registry. doi:10.1186/isrctn07607027.
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  44. ^ Sposato, Luciano A.; Kapral, Moira K.; Fang, Jiming; Gill, Sudeep S.; Hackam, Daniel G.; Cipriano, Lauren E.; Hachinski, Vladimir (1 December 2015). "Declining Incidence of Stroke and Dementia: Coincidence or Prevention Opportunity?". JAMA Neurology. 72 (12): 1529–31. doi:10.1001/jamaneurol.2015.2816. PMID 26658969.
  45. ^ Hachinski, Vladimir; the Dementia Prevention Initiative (2022-02-01). "The comprehensive, customized, cost-effective approach (CCCAP) to prevention of dementia". Alzheimer's & Dementia. 18 (8): 1565–1568. doi:10.1002/alz.12586. ISSN 1552-5260. PMID 35103397. S2CID 246444750.
  46. ^ Avan, Abolfazl; Hachinski, Vladimir; Brain Health Learn and Act Group (2021-09-27). "Brain health: Key to health, productivity, and well-being". Alzheimer's & Dementia. 18 (7): 1396–1407. doi:10.1002/alz.12478. ISSN 1552-5260. PMID 34569702. S2CID 237942165.
  47. ^ Hachinski, Vladimir (2015). "Stroke and potentially preventable dementias proclamation: updated World Stroke Day proclamation". Stroke. 46 (11): 3039–3040. doi:10.1161/strokeaha.115.011237. PMID 26504189. S2CID 36897508.
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