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1. Primordial and Primary Prevention of Ischemic Stroke in Saudi Arabia: A Combination Approach and Evolving Concepts

Author

Hussein Algahtani, Bader Shirah, and Vladimir Hachinski

Subjects
ischemic stroke, primary prevention, risk factor, saudi arabia, Medicine
Abstract

Ischemic stroke is a considerable public health hazard and a significant cause of disability and mortality in Saudi Arabia. Primary prevention strategies in the country are currently limited. With the health sector transformation program that depends on the principles of value-based care and applying the new model of care in disease prevention, aggressive and serious steps for primary stroke prevention are expected to be implemented. This article reviews primordial and primary prevention of ischemic stroke in Saudi Arabia and suggests a combination approach and framework for implementation. We provide a pragmatic solution to implement primordial and primary stroke prevention in Saudi Arabia and specify the roles of the government, health professionals, policymakers, and the entire population. Currently, there are several key priorities for primordial and primary stroke prevention in Saudi Arabia that should target people at different levels of risk. These include an emphasis on a comprehensive approach that includes both individual and population-based strategies and establishing partnerships across health-care providers to share responsibility for developing and implementing both strategies. This is an urgent call for action to initiate different strategies suggested by experts for primary stroke prevention in Saudi Arabia.

Published
2024
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3. Inequalities in health-related quality of life and functional health of an aging population: A Canadian community perspective.

Author

Sarah Singh, Shane Goodwin, Shiran Zhong, Abolfazl Avan, Kem Rogers, Vladimir Hachinski, and Stephanie Frisbee

Subjects
Medicine, Science
Abstract

BackgroundReducing health inequalities among older adults is crucial to ensuring healthy aging is within reach for all. The current study provides a timely update on demographic- and geographic-related inequalities in healthy aging among older adults residing in Canadian communities.MethodsData was extracted from the Canadian Health Survey on Seniors [2019-2020] for ~6 million adults aged 65 years and older residing in 10 provinces of Canada. Healthy aging was defined by two indices: 1] health-related quality of life and 2] functional health. Poisson regression models and spatial mapping were used to demonstrate inequalities among age, race, and sex categories, and health regions.ResultsApproximately 90.3% of individuals reported less than perfect quality of life and 18.8% reported less than perfect functional health. The prevalence of less than perfect quality of life was higher for females [PR 1.14, 95% CI;1.02-1.29] and for older adults aged ≥80 years as compared to males and older adults aged ≤79 years [PR 1.66, 95% CI;1.49-1.85]. Similarly, the prevalence of less than perfect functional health was higher for females [PR 1.58, 95% CI;1.32-1.89] and for older adults aged ≥80 years [PR 2.71, 95% CI;2.59-2.84]. Spatial mapping showed that regions of lower quality of life were concentrated in the Prairies and Western Ontario, whereas regions of higher quality of life were concentrated in Quebec.ConclusionsAmongst older individuals residing in Canadian communities, less than perfect quality of life and functional health is unequally distributed among females, older adults aged ≥80 years, and those residing in the Prairie regions specifically. Newer policy should focus on interventions targeted at these subpopulations to ensure that healthy aging in within reach for all Canadians.

Published
2024
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4. Prioritizing determinants of cognitive function in healthy middle-aged and older adults: insights from a machine learning regression approach in the Canadian longitudinal study on aging

Author

Sarah Singh, Shiran Zhong, Kem Rogers, Vladimir Hachinski, and Stephanie Frisbee

Subjects
cognitive function, determinants of health, dementia prevention, machine learning, CLSA, Public aspects of medicine, RA1-1270
Abstract

IntroductionThe preservation of healthy cognitive function is a crucial step toward reducing the growing burden of cognitive decline and impairment. Our study aims to identify the characteristics of an individual that play the greatest roles in determining healthy cognitive function in mid to late life.MethodsData on the characteristics of an individual that influence their health, also known as determinants of health, were extracted from the baseline cohort of the Canadian Longitudinal Study of Aging (2015). Cognitive function was a normalized latent construct score summarizing eight cognitive tests administered as a neuropsychological battery by CLSA staff. A higher cognitive function score indicated better functioning. A penalized regression model was used to select and order determinants based on their strength of association with cognitive function. Forty determinants (40) were entered into the model including demographic and socioeconomic factors, lifestyle and health behaviors, clinical measures, chronic diseases, mental health status, social support and the living environment.ResultsThe study sample consisted mainly of White, married, men and women aged 45–64 years residing in urban Canada. Mean overall cognitive function score for the study sample was 99.5, with scores ranging from 36.6 to 169.2 (lowest to highest cognitive function). Thirty-five (35) determinants were retained in the final model as significantly associated with healthy cognitive functioning. The determinants demonstrating the strongest associations with healthy cognitive function, were race, immigrant status, nutritional risk, community belongingness, and satisfaction with life. The determinants demonstrating the weakest associations with healthy cognitive function, were physical activity, greenness and neighborhood deprivation.ConclusionGreater prioritization and integration of demographic and socioeconomic factors and lifestyle and health behaviors, such greater access to healthy foods and enhancing aid programs for low-income and immigrant families, into future health interventions and policies can produce the greatest gains in preserving healthy cognitive function in mid to late life.

Published
2023
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5. Blood pressure trajectories over 35 years and dementia risk: A retrospective study: The HUNT study

Author

Geir Selbaek, Josephine Stuebs, Knut Engedal, Vladimir Hachinski, Knut Hestad, Cathrine Selnes Trevino, Håvard Skjellegrind, Yehani Wedatilake, and Bjørn Heine Strand

Subjects
blood pressure, dementia, trajectory, cohort study, Alzheimer, vascular dementia, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

High blood pressure is a well-established risk factor of dementia. However, the timing of the risk remains controversial. The aim of the present study was to compare trajectories of systolic blood pressure (SBP) over a 35-year follow-up period in the Health Survey in Trøndelag (HUNT) from study wave 1 to 4 in people with and without a dementia diagnosis at wave 4 (HUNT4). This is a retrospective cohort study of participants aged ≥ 70 years in HUNT4, where 9,720 participants were assessed for dementia. In the HUNT study all residents aged ≥ 20 years have been invited to four surveys: HUNT1 1984–86, HUNT2 1995–97, HUNT3 2006–08 and HUNT4 2017–19. The study sample was aged 70–102 years (mean 77.6, SD 6.0) at HUNT4, 54% were women and 15.5% had dementia, 8.8% had Alzheimer’s disease (AD), 1.6% had vascular dementia (VaD) and 5.1% had other types of dementia. Compared to those without dementia at HUNT4, those with dementia at HUNT4 had higher SBP at HUNT1 and HUNT2, but lower SBP at HUNT4. These differences at HUNT1 and 2 were especially pronounced among women. Results did not differ across birth cohorts. For dementia subtypes at HUNT4, the VaD group had a higher SBP than the AD group at HUNT2 and 3. Age trajectories in SBP showed that the dementia group experienced a steady increase in SBP until 65 years of age and a decrease from 70 to 90 years. SBP in the no- dementia group increased until 80 years before it leveled off from 80 to 90 years. The present study confirms findings of higher midlife SBP and lower late-life SBP in people with dementia. This pattern may have several explanations and it highlights the need for close monitoring of BP treatment in older adults, with frequent reappraisal of treatment needs.

Published
2022
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6. The World Stroke Organization’s Declaration for worldwide primary stroke and dementia prevention

Author

Michael Brainin, Valery l Feigin, Bo Norrving, Sheila C.O. Martins, Graeme J. Hankey, and Vladimir Hachinski

Subjects
global disease prevention, stroke, dementia, cardiovascular disease, polypill, “stroke riskometer”, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Сurrent strategies of primary stroke and cardiovascular disease prevention are aimed at addressing the main risk factors primarily in patients with higher cardiovascular disease risk. Since the number of people with incident stroke and ischaemic heart disease cases is rapidly growing across all countries of the world, this preventive strategy appears to be not sufficiently effective. World Stroke Organization recently (2020) endorsed a different concept of stroke and dementia prevention based on a population-wide approach to dealing with risk factors, which involves all individuals regardless of their cardiovascular disease risk level. This article describes four main primary prevention strategies suggested by the World Stroke Organization to effectively reduce stroke and dementia incidence by 50% and 30% respectively. These strategies include (1) population-wide prevention; (2) polypill therapy; (3) free e-Health application Stroke Riskometer; and active engagement of community health workers.

Published
2020
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7. Measurement of carotid plaque burden: A tool for predicting and preventing dementia?

Author

John J. Shin, Vladimir Hachinski, M. Reza Azarpazhooh, Aidin Shariatzadeh, and J. David Spence

Subjects
Atherosclerosis, Cognition, Dementia, Carotid plaque burden, Prediction, Prevention, Specialties of internal medicine, RC581-951, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Introduction: Carotid plaque burden is a strong predictor of stroke risk, and preventing stroke reduces the risk of dementia. Treating carotid plaque burden markedly reduces the risk of stroke. Methods: Among patients age 65–80 years attending a stroke prevention clinic, we identified those with a carotid plaque burden in the top 20% of Total Plaque Area (High TPA) and the bottom 20% (Low TPA) and performed cognitive tests: The Montreal Cognitive Assessment test (MoCA), the WAIS-III Digit Symbol-Coding Test (DSST) and Trail-Making Test (TMT) part A and B. Results: There were 31 patients recruited; 11 Low TPA (5 men) and 20 High TPA (17 men), p = 0.04. TPA was 35 ± 25 mm2 in the Low TPA vs.392 ± 169 mm2 in the High TPA group (0.0001). Patients with a high plaque burden had significantly worse performance on all the cognitive tests, all p< 0.05 Discussion: A high carotid plaque burden identifies patients at risk of cognitive impairment. Because carotid plaque burden is treatable, and treating it markedly reduces the risk of stroke, we suggest that measurement of plaque burden is a useful tool for both prediction of cognitive impairment, and prevention of dementia.

Published
2021
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8. Hypertension and Pathogenic hAPP Independently Induce White Matter Astrocytosis and Cognitive Impairment in the Rat

Author

Alexander Levit, Sonny Cheng, Olivia Hough, Qingfan Liu, Yuksel Agca, Cansu Agca, Vladimir Hachinski, and Shawn N. Whitehead

Subjects
hypertension, amyloid, astrocytes, microglia, white matter, cognitive function, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Hypertension is recognized as a risk factor for Alzheimer disease, but the causal link remains undetermined. Although astrocytes and microglia play an important role in maintaining the neurovascular unit, astrocytes and microglia have been understudied in comorbid models of hypertension and Alzheimer disease. In this study, male transgenic Fischer 344 rats (TgAPP21) overexpressing a pathogenic human amyloid precursor protein received 8 weeks of Angiotensin II infusion to increase blood pressure, and the rats were evaluated for astrocytosis, microgliosis, and cognitive function. A linear relationship between astrocytosis and blood pressure was observed in the corpus callosum and cingulum of wildtype rats, with hypertensive wildtype rats matching the elevated baseline astrocytosis seen in normotensive transgenic rats. In contrast, hypertensive transgenic rats did not demonstrate a further increase of astrocytosis, suggesting a deficient response. Angiotensin II infusion did not affect activation of microglia, which were elevated in the white matter and hippocampus of transgenic rats. Angiotensin II infusion did impair both wildtype and transgenic rats’ executive functions in the Morris Water Maze. These results present important implications for the interaction between hypertension and pathogenic human amyloid precursor protein expression, as Angiotensin II infusion produced cognitive impairments in both genotypes, but transgenic rats were additionally impaired in developing a normal astrocytic response to elevated blood pressure.

Published
2020
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9. Canadian Consensus Conference on Diagnosis and Treatment of Dementia (CCCDTD)5: Guidelines for management of vascular cognitive impairment

Author

Eric E. Smith, Philip Barber, Thalia S. Field, Aravind Ganesh, Vladimir Hachinski, David B. Hogan, Krista L. Lanctôt, M. Patrice Lindsay, Mukul Sharma, Richard H. Swartz, Zahinoor Ismail, Serge Gauthier, and Sandra E. Black

Subjects
dementia, guidelines, vascular cognitive impairment, vascular dementia, Neurology. Diseases of the nervous system, RC346-429, Geriatrics, RC952-954.6
Abstract

Abstract Introduction Vascular disease is a common cause of dementia, and often coexists with other brain pathologies such as Alzheimer's disease to cause mixed dementia. Many of the risk factors for vascular disease are treatable. Our objective was to review evidence for diagnosis and treatment of vascular cognitive impairment (VCI) to issue recommendations to clinicians. Methods A subcommittee of the Canadian Consensus Conference on Diagnosis and Treatment of Dementia (CCCDTD) reviewed areas of emerging evidence. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used to assign the quality of the evidence and strength of the recommendations. Results Using standardized diagnostic criteria, managing hypertension to conventional blood pressure targets, and reducing risk for stroke are strongly recommended. Intensive blood pressure lowering in middle‐aged adults with vascular risk factors, using acetylsalicylic acid in persons with VCI and covert brain infarctions but not if only white matter lesions are present, and using cholinesterase inhibitors are weakly recommended. Conclusions The CCCDTD has provided evidence‐based recommendations for diagnosis and management of VCI for use nationally in Canada, that may also be of use worldwide.

Published
2020
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10. Predicted Brain Age After Stroke

Author

Natalia Egorova, Franziskus Liem, Vladimir Hachinski, and Amy Brodtmann

Subjects
age prediction, structural magnetic resonance imaging, stroke, chronological age, brain age, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Aging is a known non-modifiable risk factor for stroke. Usually, this refers to chronological rather than biological age. Biological brain age can be estimated based on cortical and subcortical brain measures. For stroke patients, it could serve as a more sensitive marker of brain health than chronological age. In this study, we investigated whether there is a difference in brain age between stroke survivors and control participants matched on chronological age. We estimated brain age at 3 months after stroke, and then followed the longitudinal trajectory over three time-points: within 6 weeks (baseline), at 3 and at 12 months following their clinical event. We found that brain age in stroke participants was higher compared to controls, with the mean difference between the groups varying between 3.9 and 8.7 years depending on the brain measure used for prediction. This difference in brain age was observed at 6 weeks after stroke and maintained at 3 and 12 months after stroke. The presence of group differences already at baseline suggests that stroke might be an ultimate manifestation of gradual cerebrovascular burden accumulation and brain degeneration. Brain age prediction, therefore, has the potential to be a useful biomarker for quantifying stroke risk.

Published
2019
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11. APP21 transgenic rats develop age-dependent cognitive impairment and microglia accumulation within white matter tracts

Author

Nina Weishaupt, Qingfan Liu, Sheojung Shin, Ramandeep Singh, Yuksel Agca, Cansu Agca, Vladimir Hachinski, and Shawn Narain Whitehead

Subjects
Microglia, White matter inflammation, APP21 transgenic rat, Cognitive impairment, Alzheimer’s disease, Rat model, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background Most of the animal models commonly used for preclinical research into Alzheimer’s disease (AD) largely fail to address the pathophysiology, including the impact of known risk factors, of the widely diagnosed sporadic form of the disease. Here, we use a transgenic rat (APP21) that does not develop AD-like pathology spontaneously with age, but does develop pathology following vascular stress. To further the potential of this novel rat model as a much-needed pre-clinical animal model of sporadic AD, we characterize APP21 transgenic rats behaviorally and histologically up to 19 months of age. Methods The open field test was used as a measure of activity; and the Morris water maze was used to assess learning, memory, and strategy shift. Neuronal loss and microglia activation were also assessed throughout the brain. Results APP21 transgenic rats showed deficits in working memory from an early age, yet memory recall performance after 24 and 72 h was equal to that of wildtype rats and did not deteriorate with age. A deficit in strategy shift was observed at 19 months of age in APP21 transgenic rats compared to Fischer wildtype rats. Histologically, APP21 transgenic rats demonstrated accelerated white matter inflammation compared to wildtype rats, but interestingly no differences in neuron loss were observed. Conclusions The combined presence of white matter pathology and executive function deficits mirrored what is often found in patients with mild cognitive impairment or early dementia, and suggests that this rat model will be useful for translationally meaningful studies into the development and prevention of sporadic AD. The presence of widespread white matter inflammation as the only observed pathological correlate for cognitive deficits raises new questions as to the role of neuroinflammation in cognitive decline.

Published
2018
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12. Blood pressure at age 60–65 versus age 70–75 and vascular dementia: a population based observational study

Author

Mingkai Peng, Guanmin Chen, Karen L. Tang, Hude Quan, Eric E. Smith, Peter Faris, Vladimir Hachinski, and Norm R. C. Campbell

Subjects
Population based observational study, Blood pressure, Vascular dementia, Pulse pressure, Geriatrics, RC952-954.6
Abstract

Abstract Background Vascular dementia (VaD) is the second most common form of dementia. However, there were mixed evidences about the association between blood pressure (BP) and risk of VaD in midlife and late life and limited evidence on the association between pulse pressure and VaD. Methods This is a population-based observational study. 265,897 individuals with at least one BP measurement between the ages of 60 to 65 years and 211,116 individuals with at least one BP measurement between the ages of 70 to 75 years were extracted from The Health Improvement Network in United Kingdom. Blood pressures were categorized into four groups: normal, prehypertension, stage 1 hypertension, and stage 2 hypertension. Cases of VaD were identified from the recorded clinical diagnoses. Multivariable survival analysis was used to adjust other confounders and competing risk of death. All the analysis were stratified based on antihypertensive drug use status. Multiple imputation was used to fill in missing values. Results After accounting for the competing risk of death and adjustment for potential confounders, there was an association between higher BP levels in the age 60–65 cohort with the risk of developing VaD (hazard ratio [HR] 1.53 (95% confidence interval: 1.04, 2.25) for prehypertension, 1.90 (1.30, 2.78) for stage 1 hypertension, and 2.19 (1.48, 3.26) for stage 2 hypertension) in the untreated group. There was no statistically significant association between BP levels and VaD in the treated group in the age 60–65 cohort and age 70–75 cohort. Analysis on Pulse Pressure (PP) stratified by blood pressure level showed that PP was not independently associated with VaD. Conclusion High BP between the ages of 60 to 65 years is a significant risk for VaD in late midlife. Greater efforts should be placed on early diagnosis of hypertension and tight control of BP for hypertensive patients for the prevention of VaD.

Published
2017
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13. Does left ventricular hypertrophy affect cognition and brain structural integrity in type 2 diabetes? Study design and rationale of the Diabetes and Dementia (D2) study

Author

Sheila K. Patel, Carolina Restrepo, Emilio Werden, Leonid Churilov, Elif I. Ekinci, Piyush M. Srivastava, Jay Ramchand, Bryan Wai, Brian Chambers, Christopher J. O’Callaghan, David Darby, Vladimir Hachinski, Toby Cumming, Geoff Donnan, Louise M. Burrell, and Amy Brodtmann

Subjects
Type 2 diabetes mellitus, Dementia, Alzheimer’s disease, Left ventricular hypertrophy, Cognition, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Abstract Background Cognitive impairment is common in type 2 diabetes mellitus, and there is a strong association between type 2 diabetes and Alzheimer’s disease. However, we do not know which type 2 diabetes patients will dement or which biomarkers predict cognitive decline. Left ventricular hypertrophy (LVH) is potentially such a marker. LVH is highly prevalent in type 2 diabetes and is a strong, independent predictor of cardiovascular events. To date, no studies have investigated the association between LVH and cognitive decline in type 2 diabetes. The Diabetes and Dementia (D2) study is designed to establish whether patients with type 2 diabetes and LVH have increased rates of brain atrophy and cognitive decline. Methods The D2 study is a single centre, observational, longitudinal case control study that will follow 168 adult patients aged >50 years with type 2 diabetes: 50% with LVH (case) and 50% without LVH (control). It will assess change in cardiovascular risk, brain imaging and neuropsychological testing between two time-points, baseline (0 months) and 24 months. The primary outcome is brain volume change at 24 months. The co-primary outcome is the presence of cognitive decline at 24 months. The secondary outcome is change in left ventricular mass associated with brain atrophy and cognitive decline at 24 months. Discussion The D2 study will test the hypothesis that patients with type 2 diabetes and LVH will exhibit greater brain atrophy than those without LVH. An understanding of whether LVH contributes to cognitive decline, and in which patients, will allow us to identify patients at particular risk. Trial registration Australian New Zealand Clinical Trials Registry ( ACTRN12616000546459 ), date registered, 28/04/2016

Published
2017
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14. Inhibition of the primary motor cortex and the upgoing thumb sign

Author

Antonia Nucera, Mahmoud Reza Azarpazhooh, Lucilla Cardinali, Rasha Alsubaie, Tzu-ching Chiang, Nina Weishaupt, and Vladimir Hachinski

Subjects
Neurology. Diseases of the nervous system, RC346-429
Abstract

Background: The upgoing thumb sign has been frequently observed in patients with minor strokes and transient ischemic attacks as an indicator of brain involvement. We assessed the effect of primary motor cortex (M1) inhibition in the development of the upgoing thumb sign. Methods: Used repetitive Transcranial Magnetic Stimulation (rTMS, 1Hz frequency for 15min, 1s ISI, 900 pulses) at 60% of resting motor threshold to inhibit the right or left primary motor cortex of 10 healthy individuals. Participants were examined before and after rTMS by a neurologist who was blind to the site of motor cortex inhibition. Results: 10 neurological intact participants (5 women/5 men) were recruited for this study. 2 cases were excluded due to pre-existing possible thumb signs. After the inhibition of the primary motor cortex, in 6 subjects out of 8, we observed a thumb sign contralateral to the site of primary motor cortex inhibition. In one subject an ipsilateral thumbs sign was noted. In another case, we did not find an upgoing thumb sign. Conclusion: The upgoing thumb sign is a subtle neurological finding that may be related to the primary motor cortex or corticospinal pathways involvements. Keywords: Corticospinal tract, Upper motor neuron lesions, Primary motor cortex, Transcranial magnetic stimulation

Published
2017
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15. Cognitive changes following multiple-modality exercise and mind-motor training in older adults with subjective cognitive complaints: The M4 study.

Author

Narlon Cassio Boa Sorte Silva, Dawn P Gill, Adrian M Owen, Teresa Liu-Ambrose, Vladimir Hachinski, Ryosuke Shigematsu, and Robert J Petrella

Subjects
Medicine, Science
Abstract

We investigated the effects of multiple-modality exercise with additional mind-motor training on cognition in community-dwelling older adults with subjective cognitive complaints.Participants (n = 127, mean age 67.5 [7.3] years, 71% women) were randomized to receive 45 minutes of multiple-modality exercise with additional 15 minutes of either mind-motor training (M4, n = 63) or control (balance, range of motion and breathing exercises [M2, n = 64]). In total, both groups exercised 60 minutes/day, 3 days/week, for 24 weeks. Standardized global cognitive functioning (GCF), concentration, reasoning, planning, and memory were assessed at 24 weeks and after a 28-week no-contact follow-up.There were no significant differences in the study primary outcomes. The M4 group, however, showed trends for greater improvements in GCF and memory (both, P = .07) compared to the M2 group at 24 weeks. Significant differences between group in GCF (P = .03) and memory (P = .02) were observed after the 28-week no-contact follow-up favouring the M4 group.Additional mind-motor training did not impart immediate greater benefits to cognition among the study participants.

Published
2018
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16. Therapeutic Strategies and Drug Development for Vascular Cognitive Impairment

Author

Eric E. Smith, Alicja Cieslak, Philip Barber, Jerry Chen, Yu‐Wei Chen, Ida Donnini, Jodi D. Edwards, Richard Frayne, Thalia S. Field, Janka Hegedus, Victoria Hanganu, Zahinoor Ismail, Jamila Kanji, Makoto Nakajima, Raza Noor, Stefano Peca, Demetrios Sahlas, Mukul Sharma, Luciano A. Sposato, Richard H. Swartz, Charlotte Zerna, Sandra E. Black, and Vladimir Hachinski

Subjects
cerebrovascular disease, clinical trials, cognitive impairment, stroke, systematic review, vascular dementia, Diseases of the circulatory (Cardiovascular) system, RC666-701
Published
2017
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17. Effects of pyrrolidine dithiocarbamate on beta-amyloid (25–35)-induced inflammatory responses and memory deficits in the rat

Author

Guanliang Cheng, Shawn N. Whitehead, Vladimir Hachinski, and David F. Cechetto

Subjects
Pyrrolidine dithiocarbamate, Beta-amyloid, Glial cell activation, Neuroinflammation, Learning and spatial memory deficits, Alzheimer disease, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

It has been well established that neuroinflammation is involved in Alzheimer disease (AD) pathogenesis. Accumulation and aggregation of beta-amyloid (Aβ) peptide in the brains of patients with AD result in activation of glial cells which, in turn, initiates neuroinflammatory responses that involve reactive oxygen intermediates and release of inflammatory cytokines. In this study, bilateral intracerebroventricular (icv) injections of Aβ (25–35) in the rat resulted in impairment in learning and spatial memory and increased immunoreactive staining of AD-related neuropathological markers (Aβ, APP) and inflammatory mediators (OX-6, COX-2) in CA1 and dentate gyrus regions of the hippocampus. Pyrrolidine dithiocarbamate (PDTC) given intraperitoneally 30 min before Aβ injection and daily for 7 days postsurgery significantly prevented Aβ-induced neuropathological and neuroinflammatory responses, as well as the learning and spatial memory deficits. The potential of PDTC for reducing cognitive and neuropathological deficits may provide preliminary evidence for a new approach of AD treatment.

Published
2006
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18. Vitamin D and caudal primary motor cortex: a magnetic resonance spectroscopy study.

Author

Cedric Annweiler, Olivier Beauchet, Robert Bartha, Vladimir Hachinski, Manuel Montero-Odasso, and WALK Team (Working group Angers-London for Knowledge)

Subjects
Medicine, Science
Abstract

Vitamin D is involved in brain physiology and lower-extremity function. We investigated spectroscopy in a cohort of older adults to explore the hypothesis that lower vitamin D status was associated with impaired neuronal function in caudal primary motor cortex (cPMC) measured by proton magnetic resonance spectroscopic imaging.Twenty Caucasian community-dwellers (mean±standard deviation, 74.6±6.2 years; 35.0% female) from the 'Gait and Brain Study' were included in this analysis. Ratio of N-acetyl-aspartate to creatine (NAA/Cr), a marker of neuronal function, was calculated in cPMC. Participants were categorized according to mean NAA/Cr. Lower vitamin D status was defined as serum 25-hydroxyvitamin D (25OHD) concentration

Published
2014
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19. Vascular cognitive impairment (VCI): Progress towards knowledge and treatment

Author

Silvia Di Legge and Vladimir Hachinski

Subjects
cerebrovascular disease, dementia, vascular cognitive impairment, diagnostic criteria, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Abstract Until recently, the study of cognitive impairment as a manifestation of cerebrovascular disease (CVD) has been hampered by the lack of common standards for assessment. The term vascular cognitive impairment (VCI) encompasses all levels of cognitive decline associated with CVD from mild deficits in one or more cognitive domains to crude dementia syndrome. VCI incorporates the complex interactions among classic vascular risk factors (i.e. arterial hypertension, high cholesterol, and diabetes), CVD subtypes, and Alzheimer's Disease (AD) pathology. VCI may be the earliest, commonest, and subtlest manifestation of CVD and can be regarded as a highly prevalent and preventable syndrome. However, cognition is not a standardized outcome measure in clinical trials assessing functional ability after stroke. Furthermore, with the exception of anti-hypertensive medications, the impact of either preventive or acute stroke treatments on cognitive outcome is not known. Although clinical, epidemiological, neuroimaging, and experimental data support the VCI concept, there is a lack of integrated knowledge on the role played by the most relevant pathophysiological mechanisms involved in several neurological conditions including stroke and cognitive impairment such as excitotoxicity, apoptosis, mitochondrial DNA damage, oxidative stress, disturbed neurotransmitter release, and inflammation. For this reason, in 2006 the National Institute of Neurological Disorders and Stroke (NINDS) and the Canadian Stroke Network (CSN) defined a set of data elements to be collected in future studies aimed at defining VCI etiology, clinical manifestations, predictive factors, and treatment. These recommendations represent the first step toward developing diagnostic criteria for VCI based on sound knowledge rather than on hypotheses. The second step will be to integrate all studies using the agreed methodologies. This is likely to accelerate the search for answers.

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20. The convergence of stroke and dementia

Author

Vladimir Hachinski

Subjects
acidente vascular cerebral, demência, prevenção, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

ABSTRACT Neurological disorders account for the most Disability Adjusted Life Years (DALY's) -of the Global Burden of Disease (10%). More than half of neurological DALY's result from the combination of stroke (42%) and dementia (10%). The two pose risk for each other and share the same predisposing factors. A stroke doubles the risk of dementia. The close interactions call for convergent approaches. Stroke and dementia also converge at the microscopic level. The neurovascular unit has emerged as a key organizational structure of the brain. Involvement of any of its elements affects all the others. Thus, neurodegeneration impairs the microcirculation and disturbances of the microcirculation accelerate neurodegeneration. Evolving technologies allow “in vivo” imaging of the usual mixture of vascular and neurodegenerative pathology of the elderly that makes them prone to stroke and dementia. Since they occur together, they should be prevented together with a multimodal approach of lifestyle changes and mechanistic therapeutic targets. The two fields are also converging at the policy level. The World Stroke Organization has updated its Proclamation to include potentially preventable dementias that has been endorsed by Alzheimer Disease International, The World Federation of Neurology, the American Academy of Neurology and 20 international, regional and national organizations. Those interested in stroke and those dealing with dementia should work together where they can, differ where they must, with the common aim of preventing jointly, both stroke and dementia.

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21. Frequency and Underlying Pathology of Pure Vascular Cognitive Impairment

Author

Shahram Oveisgharan, Robert J. Dawe, Lei Yu, Alifiya Kapasi, Konstantinos Arfanakis, Vladimir Hachinski, Julie A. Schneider, and David A. Bennett

Subjects
Aged, 80 and over, Male, Cerebrovascular Disorders, Alzheimer Disease, Humans, Brain, Female, Cognitive Dysfunction, Neurology (clinical), Neuropsychological Tests
Abstract

ImportanceIt is not clear how common pure vascular cognitive impairment (VCI) is in the absence of Alzheimer disease (AD) and/or other neurodegenerative pathologies.ObjectiveTo identify participants without AD and other neurodegenerative pathologies and determine the extent to which cerebrovascular disease pathologies were associated with cognitive impairment.Design, Setting, and ParticipantsThis clinical pathological study included participants from 2 ongoing community-based cohorts that began enrollment in 1994 and 1997. Prior to death, participants were observed for a mean (SD) of 8.4 (5.3) years with annual assessments. From 2096 participants who died, 1799 (85.8%) underwent autopsy and 1767 had complete postmortem pathological examination data at the time of data analyses. To identify participants without neurodegenerative pathologies, we categorized them in 3 subgroups. A vascular subgroup was composed of participants without significant levels of neurodegenerative brain pathologies. A neurodegenerative subgroup was composed of participants without significant levels of cerebrovascular disease pathologies. A mixed subgroup was composed of the rest of the participants. Data were analyzed from May 2021 to July 2022.ExposuresBrain pathology indices obtained by postmortem pathological assessments.Main Outcomes and MeasuresThe primary outcome was cognitive impairment defined by presence of mild cognitive impairment or dementia. The secondary outcome was cognition assessed by 19 neuropsychological tests.ResultsOf 1767 included participants, 1189 (67.3%) were women, and the mean (SD) age at death was 89.4 (6.6) years. In the vascular subgroup (n = 369), cognitive impairment was present in 156 participants (42.3%) and was associated with cerebrovascular disease pathologies (macroinfarcts: odds ratio [OR], 2.05; 95% CI, 1.49-2.82; P P = .03) but not AD or other neurodegenerative pathologies, an indication of pure VCI. In mixed-effects models including all the pathologies, only macroinfarcts were associated with a faster cognitive decline rate (estimate, −0.019; SE, 0.005; P Conclusions and RelevanceIn this study, pure VCI was not rare. Macroinfarcts, specifically in frontal white matter, were the main cerebrovascular disease pathologies associated with cognitive decline in pure VCI.

Published
2023

23. Use of multidimensional item response theory methods for dementia prevalence prediction: an example using the Health and Retirement Survey and the Aging, Demographics, and Memory Study.

Author

Emma Nichols, Foad Abd-Allah, Amir Abdoli, Ahmed Abualhasan, Eman Abu-Gharbieh, Ashkan Afshin, Rufus Akinyemi, Fahad Mashhour Alanezi, Vahid Alipour, Amir Almasi-Hashiani, Jalal Arabloo, Amir Ashraf-Ganjouei, Getinet Ayano, José Luis Ayuso-Mateos, Atif Amin Baig, Maciej Banach, Miguel A. Barboza, Suzanne Lyn Barker-Collo, Bernhard T. Baune, Akshaya Srikanth Bhagavathula, Krittika Bhattacharyya, Ali Bijani, Atanu Biswas, Archith Boloor, Carol Brayne, Hermann Brenner, Katrin Burkart, Sharath Burugina Nagaraja, Felix Carvalho, Luis F. S. Castro-de-Araujo, Ferrán Catalá-López, Ester Cerin, Nicolas Cherbuin, Dinh-Toi Chu, Xiaochen Dai, Antonio Reis de Sá-Junior, Shirin Djalalinia, Abdel Douiri, David Edvardsson, Shaimaa I. El-Jaafary, Sharareh Eskandarieh, Andre Faro, Farshad Farzadfar, Valery Feigin, Seyed-Mohammad Fereshtehnejad, Eduarda Fernandes, Pietro Ferrara 0002, Irina Filip, Florian Fischer, Shilpa Gaidhane, Lucia Galluzzo, Gebreamlak Gebremedhn Gebremeskel, Ahmad Ghashghaee, Alessandro Gialluisi, Elena V. Gnedovskaya, Mahaveer Golechha, Rajeev Gupta, Vladimir Hachinski, Mohammad R. Haider, Teklehaimanot Gereziher Haile, Mohammad Hamiduzzaman, Graeme J. Hankey, Simon I. Hay, Golnaz Heidari, Reza Heidari-Soureshjani, Hung Chak Ho, Mowafa S. Househ, Bing-Fang Hwang, Licia Iacoviello, Olayinka Stephen Ilesanmi, Irena M. Ilic, Milena D. Ilic, Seyed Sina Naghibi Irvani, Masao Iwagami, Ihoghosa Osamuyi Iyamu, Ravi Prakash Jha, Rizwan Kalani, André Karch, Ayele Semachew Kasa, Yousef S. Khader, Ejaz Ahmad Khan, Mahalaqua Nazli Khatib, Yun Jin Kim, Sezer Kisa, Adnan Kisa, Mika Kivimäki, Ai Koyanagi, Manasi Kumar, Iván Landires, Savita Lasrado, Bingyu Li, Stephen S. Lim, Xuefeng Liu, Shilpashree Madhava Kunjathur, Azeem Majeed, Preeti Malik, Man Mohan Mehndiratta, Ritesh G. Menezes, Yousef Mohammad, Salahuddin Mohammed, Ali H. Mokdad, Mohammad Ali Moni, Gabriele Nagel, Muhammad Naveed 0005, Vinod C. Nayak, Cuong Tat Nguyen, Thi Lan Huong Nguyen, Virginia Nunez-Samudio, Andrew T. Olagunju, Samuel M. Ostroff, Nikita Otstavnov, Mayowa Owolabi, Fatemeh Pashazadeh Kan, Urvish K. Patel, Michael R. Phillips, Michael A. Piradov, Constance Dimity Pond, Faheem Hyder Pottoo, Sergio I. Prada, Amir Radfar, Fakher Rahim, Juwel Rana, Vahid Rashedi, Salman Rawaf, David Laith Rawaf, Nickolas Reinig, Andre M. N. Renzaho, Nima Rezaei, Aziz Rezapour, Michele Romoli, Gholamreza Roshandel, Perminder S. Sachdev, Amirhossein Sahebkar, Mohammad Ali Sahraian, Mehrnoosh Samaei, Mete Saylan, Feng Sha, Masood Ali Shaikh, Kenji Shibuya, Mika Shigematsu, Jae Il Shin, Rahman Shiri, Diego Augusto Santos Silva, Jasvinder A. Singh, Deepika Singhal, Valentin Yurievich Skryabin, Anna Aleksandrovna Skryabina, Amin Soheili, Houman Sotoudeh, Emma Elizabeth Spurlock, Cassandra E. I. Szoeke, Rafael Tabarés-Seisdedos, Biruk Wogayehu Taddele, Marcos Roberto Tovani-Palone, Gebiyaw Wudie Tsegaye, Marco Vacante, Narayanaswamy Venketasubramanian, Simone Vidale, Vasily Vlassov, Giang Thu Vu, Yuan-Pang Wang, Jordan Weiss, Abrha Hailay Weldemariam, Ronny Westerman, Anders Wimo, Andrea Sylvia Winkler, Chenkai Wu, Ali Yadollahpour, Metin Yesiltepe, Naohiro Yonemoto, Chuanhua Yu, Mikhail Sergeevich Zastrozhin, Anasthasia Zastrozhina, Zhi-Jiang Zhang, Christopher J. L. Murray, and Theo Vos

Published
2021
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25. The Brain Research Africa Initiative (BRAIN)

Author

Alfred K Njamnshi, Leonard Ngarka, Wepnyu Y Njamnshi, Nene Ahidjo, Joelle N Chabwine, Vladimir Hachinski, Jean Marie Annoni, Joelle Nsimire Chabwine, Alfred Kongnyu Njamnshi, Wepnyu Yembe Njamnshi, Stephen Perrig, and Roman Sztajzel

Subjects
Neurology (clinical)
Published
2023

26. Expanding the horizon of research into the pathogenesis of the white matter diseases: Proceedings of the 2021 Annual Workshop of the Albert Research Institute for White Matter and Cognition

Author

Askiel Bruno, Kai Hei Tse, Farzaneh A. Sorond, Jodi D. Edwards, Giuseppe Faraco, Anna Csiszar, Donna M. Wilcock, Zoltan Ungvari, Andy Y. Shih, Shawn N. Whitehead, S. Thomas Carmichael, Vladimir Hachinski, Deborah Gustafson, Gary A. Rosenberg, Frank C. Barone, Jeffrey M. Burns, Fanny M. Elahi, Douglas B. Gould, and Kristen L. Zuloaga

Subjects
Neurodegenerative disease/injury, Aging, Geroscience, Dementia, Vascular, White matter, Academies and Institutes, Library science, AD, Cognition, VCID, Prevention of dementia, medicine.anatomical_structure, Leukoencephalopathies, White Matter Diseases, White matter degeneration, medicine, Humans, Original Article, Geriatrics and Gerontology, Health risk, Cognitive impairment
Abstract

White matter pathologies are critically involved in the etiology of vascular cognitive impairment-dementia (VCID), Alzheimer's disease (AD), and Alzheimer's disease and related diseases (ADRD), and therefore need to be considered a treatable target ( Roseborough A, Hachinski V, Whitehead S. White matter degeneration - a treatable target? Roseborough et al. JAMA Neurol [Internet]. 2020 Apr 27;77(7):793-4, [1] . To help address this often-missed area of research, several workshops have been sponsored by the Leo and Anne Albert Charitable Trust since 2015, resulting in the incorporation of "The Albert Research Institute for White Matter and Cognition" in 2020. The first annual "Institute" meeting was held virtually on March 3-4, 2021. The Institute provides a forum and workspace for communication and support of the advancement of white matter science and research to better understand the evolution and prevention of dementia. It serves as a platform for young investigator development, to introduce new data and debate biology mechanisms and new ideas, and to encourage and support new research collaborations and directions to clarify how white matter changes, with other genetic and health risk factors, contribute to cognitive impairment. Similar to previous Albert Trust-sponsored workshops (Barone et al. in J Transl Med 14:1-14, [2]; Sorond et al. in GeroScience 42:81-96, [3]), established expert investigators were identified and invited to present. Opportunities to attend and present were also extended by invitation to talented research fellows and younger scientists. Also, updates on institute-funded research collaborations were provided and discussed. The summary that follows is a synopsis of topics and discussion covered in the workshop.

Published
2021

28. The Association between Multimorbidity and Cognitive Decline: A Systematic Review

Author

Juan‐Camilo Vargas‐González, Saverio Stranges, Mark R. Speechley, Mark J. Daley, Jason Were, Ishor Sharma, and Vladimir Hachinski

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published
2022

29. Precocious White Matter Inflammation and Behavioural Inflexibility Precede Learning and Memory Impairment in the TgAPP21 Rat Model of Alzheimer Disease

Author

Cansu Agca, Youngkyung Jung, Olivia Hough, Shawn N. Whitehead, Vladimir Hachinski, Yuksel Agca, Brian L. Allman, Andrew Gibson, and Alexander Levit

Subjects
Male, Aging, medicine.medical_specialty, Neuroscience (miscellaneous), Morris water navigation task, Corpus callosum, Corpus Callosum, Discrimination Learning, White matter, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Alzheimer Disease, Internal medicine, medicine, Animals, Memory impairment, Maze Learning, Neuroinflammation, 030304 developmental biology, Memory Disorders, 0303 health sciences, Microglia, business.industry, medicine.disease, White Matter, Rats, Inbred F344, Rats, Disease Models, Animal, Endocrinology, medicine.anatomical_structure, Neurology, Ageing, Rats, Transgenic, Alzheimer's disease, business, 030217 neurology & neurosurgery
Abstract

Neuroinflammation and behavioural inflexibility are both common in late adulthood but far more profound in Alzheimer disease (AD). To investigate the relationship between ageing, AD, neuroinflammation, and behavioural flexibility, male wild-type Fischer 344 (Wt) and the transgenic APP21 (TgAPP21) rats were aged to 4, 8, 13, and 22 months and evaluated for neuroinflammation and cognitive impairment. TgAPP21 rats overexpress a pathogenic variant of the human amyloid precursor protein (hAPP; Swedish and Indiana mutations) but do not spontaneously develop overt pathology related to AD. In both genotypes, learning and memory were similarly impaired in older rats. However, at 8 months of age, TgAPP21 rats demonstrated behavioural inflexibility in set shifting, reversal, and the Morris water maze, while Wt rats showed inflexibility at 13 and 22 months of age. This early inflexibility in TgAPP21 rats was accompanied by a precocious increase in microglia activation within the corpus callosum; 8- and 13-month-old TgAPP21 rats had similar levels of microglia activation as 13- and 22-month-old Wt rats, respectively. However, while neuroinflammation within the white matter continued to progress with age, behavioural inflexibility peaked in 8-month-old TgAPP21 rats; in older TgAPP21 rats, memory and learning impairments masked inflexibility. These findings suggest that the behavioural inflexibility and white matter inflammation seen in normal ageing are accelerated in AD and may precede impairments of learning and memory.

Published
2021

30. The apathy, gait impairment, and executive dysfunction (AGED) triad vascular variant

Author

Vladimir Hachinski, Elizabeth Finger, Frederico Pieruccini‐Faria, and Manuel Montero‐Odasso

Subjects
hypertension, Epidemiology, Health Policy, Apathy, Executive dysfunction, Brain, apathy, Basal Ganglia, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, gait impairment, prevention, Perspective, Humans, Cognitive Dysfunction, Neurology (clinical), Geriatrics and Gerontology, ambibaric brain, Gait, Aged
Abstract

Apathy, gait disturbances, and executive dysfunction (AGED) often occur together. Although they can arise independently, the presence of one might portend another. This recognition suggests the possible etiology. We focus on the most common, the vascular. We explain the AGED vascular mechanism through the ambibaric brain concept. The brain contains two complementary blood pressure systems: One high in the primitive brain (brainstem, basal ganglia, and thalamus) and a low-pressure system in the Homo sapiens brain (cerebral hemispheres). Hypertension inflicts the most damage on the primitive brain. The frontal systems connect to the basal ganglia, then the thalamus and back to the cortex. Many connections converge on the primitive brain where they are damaged by vascular disease. We need methods of determining optimal, individual blood pressures. Although the AGED triad can result from other causes, it should first signal a vascular etiology, the most prevalent, treatable, and preventable one.

Published
2022

31. We are preventing some dementias now-But how? The Potamkin lecture

Author

Vladimir, Hachinski

Abstract

Most dementias are untreatable and their prevalence is increasing around the world. However, the incidence of dementia is declining in some countries. We need to find out urgently why and how and apply the lessons promptly and widely. Given the multiplicity and variability of environmental, socioeconomic, and individual risk and protective factors, the approach needs to be comprehensive, customized to work in a particular setting, and cost effective, to justify the needed funding. Stroke, heart disease, and dementia share the same major preventable risk and protective factors and pose risks for each other. Preventing them together might result in efficiencies and economies of scale. Prevention can best occur in existing actionable population health units through established leaders in government, non-governmental organizations, and the community, around a positive message of promoting brain health as the key to health, productivity, and well-being.

Published
2022

32. A new definition of brain reserve

Author

Vladimir Hachinski and Abolfazl Avan

Subjects
Aging, Epidemiology, Health Policy, Brain, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Cognition, Cognitive Reserve, Developmental Neuroscience, Humans, Cognitive Dysfunction, Neurology (clinical), Geriatrics and Gerontology, Exercise
Abstract

Brain reserve definitions foster debate and disagreements. A consensus definition of brain reserve would fill gaps in converging ongoing research and action plans to promote brain health. Different terms are used for the capacity to adapt to life hardships and cognitive and social compliance and to neutralize or compensate for age-related neurological degeneration to prevent impaired cognition. Brain reserve, resilience, cognitive reserve, and brain maintenance have been used usually in isolation, but at times interchangeably. However, the need remains for a simplified overarching definition of brain reserve. Brain health is a continuous development and exercise of the brain, and thus the brain reserve requires a definition encompassing this continuum. We propose for discussion a new definition of brain reserve that incorporates available definitions and emphasizes the dynamic and interactive nature of a healthy brain. Brain reserve is the lifelong, dynamic, interactive, accumulating capacity to resist physical, emotional, and/or social harms.

Published
2022

33. Brain Health—Curbing Stroke, Heart Disease, and Dementia

Author

Vladimir Hachinski

Subjects
Gerontology, medicine.medical_specialty, Neurology, Heart Diseases, Heart disease, business.industry, media_common.quotation_subject, Disease, medicine.disease, Stroke, Health care, Humans, Medicine, Dementia, Neurology (clinical), Psychological resilience, Alzheimer's disease, business, media_common
Abstract

There is no health without brain health, which is threatened by rising curves of stroke, ischemic heart disease, and dementia (the triple threat). The fastest growing and intractable threat has been dementia. Focusing on finding a drug to stop Alzheimer disease has yielded growing knowledge but no treatments, partly because in the elderly, cognitive impairment results from multiple interactive pathologies aggravated by fragility and tempered by resilience on the advancing background of aging. The concept of vascular cognitive impairment (VCI) cuts pragmatically through this complexity. VCI is any cognitive impairment caused by or associated with vascular factors. It spans the spectrum of undetected cognitive impairment to full-blown dementia. The vascular component represents the only major current, treatable, and preventable contributor to dementia and offers the possibility of delaying, mitigating, or preventing more dementias in the near future. The triple threat conditions share the same protective and treatable risk factors and can be prevented together. The approach needs to be comprehensive, identifying all relevant environmental, socioeconomic, health care, and individual factors; targeted, as risks and protective factors differ among populations and individuals; and and investment valued, yielding worthwhile returns in terms of money, effort, or time. The World Stroke Organization's proclamation calling for the joint prevention of stroke and potentially preventable dementias has been endorsed by 23 international, regional, and national brain and heart organizations, including the American Academy of Neurology. We need to develop joint prevention programs to curb the triple threat. Millions of brains depend on it.

Published
2021

34. Global, regional, and national trends of dementia incidence and risk factors, 1990-2019: A Global Burden of Disease study

Author

Abolfazl Avan and Vladimir Hachinski

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Abstract

An ample literature documents the growing prevalence of dementia and associated costs. Less attention has been paid to decreased dementia incidence in some countries.We analyzed trends in age-standardized dementia, stroke, and ischemic heart disease (the triple threat) incidence rates and population attributable fraction of death and disability attributable to 12 risk factors in 204 countries and territories and 51 regions using Global Burden of Disease 2019 data.During 1990 to 2019, dementia incidence declined in 71 countries; 18 showed statistically significant declines, ranging from -12.1% (95% uncertainty intervals -16.9 to -6.8) to -2.4% (-4.6 to -0.5). During 2010 to 2019, 16 countries showed non-significant declines. Globally, the burden of the triple threat attributable to air pollution, dietary risks, non-optimal temperature, lead exposure, and tobacco use decreased from 1990 to 2019.The declining incidence of dementia in some countries, despite growing prevalence, is encouraging and urges further investigation.

Published
2022

35. The New Brain Age

Author

Vladimir Hachinski

Subjects
Post-Acute COVID-19 Syndrome, Artificial Intelligence, Brain, COVID-19, Humans, Neurology (clinical), Pandemics
Abstract

The pandemic is transforming neurology. Long COVID will linger, neurologic diseases will increase, and technology, artificial intelligence, and new virtual worlds will usher a new age of the brain and new roles for neurologists. The pandemic has compelled international collaboration, greatly increased communications, and accelerated drug and vaccines approvals. It also dramatized the close interconnection of cognitive, mental, and social health and their relevance to building back better health, education, work, and leisure. Brain health is the key to health, productivity, and well-being. Neurologists are best placed to lead brain knowledge integration and application through the unifying theme of brain health by becoming advocates, healers, and guardians of the brain.

Published
2022

36. From Dementia to Eumentia: A New Approach to Dementia Prevention

Author

Vladimir Hachinski and Abolfazl Avan

Subjects
Stroke, Heart Diseases, Epidemiology, Alzheimer Disease, Humans, Cognitive Dysfunction, Neurology (clinical), Life Style, Aged
Abstract

Background: During the past 40 years, dementia prevention approaches have ranged from searching for a drug to prevent progression to Alzheimer’s disease to preventing dementia through multidomain lifestyle interventions. Current Approaches: The search for a silver bullet has yielded good science but no clinical results. The multi-model lifestyle intervention approach has shown encouraging results. The largest proportion of resources in prevention have been devoted to finding a drug to prevent, mitigate, or delay what is being called “Alzheimer’s disease of late onset.” The reality is that Alzheimer’s pathology is common among the elderly, but it seldom only occurs alone. The only treatable and preventable pathology currently is vascular. Hence arose the concept of “vascular cognitive impairment” meaning any vascular cause or risk factor associated with cognitive impairment. The majority of cases of cognitive impairment in the elderly have a vascular component that is treatable and preventable and identifiable by several means, including a simple ischemic score. Conclusion: Since environmental, socioeconomic, and individual risk factors contribute to dementia, we proposed a Comprehensive, Customized, Cost-effective APProach (the CCC-APP) implemented in actionable units with the focus on promoting brain health (eumentia). Key Messages: We should implement dementia prevention approaches in actionable units around optimal brain health or eumentia. Heart disease, stroke, and dementia share mostly the same risk and protective factors; thus, their joint prevention is desirable. We need a comprehensive, customized, and cost-effective approach to joint prevention of stroke, heart disease, and dementia. We call for literal and virtual meetings of researchers of all the relevant disciplines to work on operational definitions and interdisciplinary collaborations.

Published
2022

37. Brain, heart, and sudden death

Author

Shahram Oveisgharan, Fariborz Ghaffarpasand, Peter Sörös, Mustafa Toma, Nizal Sarrafzadegan, and Vladimir Hachinski

Subjects
Heart Failure, Stroke, Sudden Death, Epilepsy, Neurology, Takotsubo Cardiomyopathy, Psychological Stress, Neurology (clinical), Nervous System Diseases
Abstract

During the past 30 years, rate of coronary artery disease (CAD), as the main cause of sudden death (SD), has decreased more than rate of SD. Likewise, cause of SD remains elusive in not a trivial portion of its victims. One possible reason is attention to only one organ, the heart, as the cause of SD. In fact, SD literature focuses more on the heart, less on the brain, and seldom on both. A change is required. In this paper, we first review the pathological findings seen in heart autopsies of SD victims after psychological stressors such as physical assault victims without internal injuries. Then, we summarize new studies investigating brain areas, like the insula, whose malfunctions and injuries are related to SD. Next, we review prototypes of neurological diseases and psychological stressors associated with SD and look at heart failure (HF)-related SD providing evidence for the brain-heart connection. Finally, we propose a new look at SD risk factors considering both brain and heart in their association with SD, and review strategies for prevention of SD from this perspective.

Published
2022

38. Dual decline in gait speed and cognition is associated with future dementia: evidence for a phenotype

Author

Frederico Pieruccini-Faria, Susan W. Muir-Hunter, Amit X. Garg, Jennie Wells, Michael Borrie, Louis Bherer, Yanina Sarquis-Adamson, Manuel Montero-Odasso, Richard Camicioli, Nick W. Bray, Mark Speechley, Qu Tian, Vladimir Hachinski, Joel Mahon, Stephanie Cullen, Josh Titus, and Luigi Ferrucci

Subjects
Male, Gerontology, Aging, 03 medical and health sciences, Cognition, 0302 clinical medicine, medicine, Humans, Dementia, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Gait, Aged, Proportional hazards model, business.industry, General Medicine, medicine.disease, Explained variation, Walking Speed, Preferred walking speed, Phenotype, Female, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, Dyslipidemia, Cohort study
Abstract

Background concurrent declines in gait speed and cognition have been associated with future dementia. However, the clinical profile of ‘dual decliners’, those with concomitant decline in both gait speed and cognition, has not been yet described. We aimed to describe the phenotype and the risk for incident dementia of those who present with dual decline in comparison with non-dual decliners. Methods prospective cohort of community-dwelling older adults free of dementia at baseline. We evaluated participants’ gait speed, cognition, medical status, functionality, incidence of adverse events and dementia, biannually over 7 years. Gait speed was assessed with a 6-m electronic walkway and global cognition using the MoCA test. We compared characteristics between dual decliners and non-dual decliners using t-test, chi-square and hierarchical regression models. We estimated incident dementia using Cox models. Results among 144 participants (mean age 74.23 ± 6.72 years, 54% women), 17% progressed to dementia. Dual decliners had a 3-fold risk (HR: 3.12, 95%CI: 1.23–7.93, P = 0.017) of progression to dementia compared with non-dual decliners. Dual decliners were significantly older with a higher prevalence of hypertension and dyslipidemia (P = 0.002). Hierarchical regression models show that age and sex alone explained 3% of the variation in the dual decliners group. Adding hypertension and dyslipidemia increased the explained variation by 8 and 10%, respectively. The risk of becoming a dual decliner was 4-fold higher if hypertension was present. Conclusion older adults with a concurrent decline in gait speed and cognition represent a group at the highest risk of progression to dementia. Older adults with dual decline have a distinct phenotype with a higher prevalence of hypertension, a treatable condition.

Published
2020

39. Stroke : The Essential Journal

Author

Vladimir Hachinski

Subjects
Advanced and Specialized Nursing, medicine.medical_specialty, business.industry, medicine, MEDLINE, Historical Article, Neurology (clinical), Cardiology and Cardiovascular Medicine, medicine.disease, Intensive care medicine, business, Stroke
Published
2020

40. Intravenous Thrombolysis After First-Ever Ischemic Stroke and Reduced Incident Dementia Rate

Author

Joshua O. Cerasuolo, Jennifer Mandzia, Lauren E. Cipriano, Moira K. Kapral, Jiming Fang, Vladimir Hachinski, and Luciano A. Sposato

Subjects
Advanced and Specialized Nursing, Aged, 80 and over, Male, Middle Aged, Brain Ischemia, Cohort Studies, Stroke, Treatment Outcome, Fibrinolytic Agents, Tissue Plasminogen Activator, Humans, Dementia, Female, Thrombolytic Therapy, Neurology (clinical), Cardiology and Cardiovascular Medicine, Aged, Ischemic Stroke
Abstract

Background: The use of intravenous thrombolysis is associated with improved clinical outcomes. Whether thrombolysis is associated with reduced incidence of poststroke dementia remains uncertain. We sought to estimate if the use of thrombolysis following first-ever ischemic stroke was associated with a reduced rate of incident dementia using a pragmatic observational design. Methods: We included first-ever ischemic stroke patients from the Ontario Stroke Registry who had not previously been diagnosed with dementia. The primary outcome was incident dementia ascertained by a validated diagnostic algorithm. We employed inverse probability of treatment-weighted Cox proportional hazard models to estimate the cause-specific hazard ratio for the association of thrombolysis and incident dementia at 1 and 5 years following stroke. Results: From July 2003 to March 2013, 7072 patients with ischemic stroke were included, 3276 (46.3%) were female and mean age was 71.0 (SD, 12.8) years. Overall, 38.2% of the cohort (n=2705) received thrombolysis, 77.2% (n=2087) of which was administered within 3 hours of stroke onset. In the first year following stroke, thrombolysis administration was associated with a 24% relative reduction in the rate of developing dementia (cause-specific hazard ratio, 0.76 [95% CI, 0.58–0.97]). This association remained significant at 5 years (cause-specific hazard ratio, 0.79 [95% CI, 0.66–0.91]) and at the end of follow-up (median 6.3 years; cause-specific hazard ratio, 0.79 [95% CI, 0.68–0.89]). Conclusions: Thrombolysis administration following first-ever ischemic stroke was independently associated with a reduced rate of dementia. Incident dementia should be considered as a relevant outcome when evaluating risk/benefit of thrombolysis in ischemic stroke patients.

Published
2021

41. The comprehensive, customized, cost-effective approach (CCCAP) to prevention of dementia

Author

Vladimir, Hachinski

Subjects
Stroke, Alzheimer Disease, Cost-Benefit Analysis, Humans, Cognitive Dysfunction, Dementia
Abstract

The Food and Drug Administration's controversial approval of aducanumab has sounded a wake-up call. Is the search of a silver bullet to stop Alzheimer's disease the only way to prevent dementia? The controversies and costs have opened minds to alternative approaches, the most promising being that we are already preventing some dementias in some high-income countries but do not know yet how. This article proposes one way. It requires that the approach be (1) comprehensive, taking into account all relevant environmental, socioeconomic, and individual risk and protective factors; (2) customized, because contributing factors vary by region and among individuals; and (3) cost effective, implemented in actionable units. Savings of scale could occur by preventing stroke, heart disease, and dementia together. They share the same risk factors and pose risks for each other. Brain health could be the unifying, motivating, and actionable key to health, productivity, and well-being.

Published
2021

42. Air Pollution and Incidence of Dementia: A Systematic Review and Meta-analysis

Author

Ehsan Abolhasani, Vladimir Hachinski, Nargess Ghazaleh, Mahmoud Reza Azarpazhooh, Naghmeh Mokhber, and Janet Martin

Subjects
Neurology (clinical)
Abstract

Background and ObjectivesStudies of association between air pollution and incidence of dementia have shown discrepant results. The aim of this study was to evaluate the association between air pollution and dementia.MethodsIn this systematic review and meta-analysis, PubMed, MEDLINE, EMBASE, PsycINFO, Scopus, and Web of Science were searched and updated in August 2021. Population-based cohort studies that reported on hazard ratio (HR) of dementia in association with exposure to fine particulate matter (PM2·5), nitrogen oxides (NOX), nitrogen dioxide (NO2), or ozone (O3) in those aged >40 years were included. Data were extracted by 2 independent investigators. The main outcome was the pooled HR for dementia per increment of pollutant, calculated using a random-effects model. Results were reported in accordance with PRISMA guidelines. The protocol was registered in PROSPERO (registration number: CRD42020219036).ResultsA total of 20 studies were included in the systematic review, and 17 provided data for the meta-analysis. The total included population was 91,391,296, with 5,521,111 (6%) being diagnosed with dementia. A total of 12, 5, 6, and 4 studies were included in the meta-analyses of PM2·5, NOX, NO2, and O3, respectively. The risk of dementia increased by 3% per 1 μg/m3increment in PM2·5(HR, 1.03; 95% CI [1.02–1.05]; I2= 100%). The association between dementia per 10 μg/m3increment in NOX(HR, 1.05; 95% CI [0.99–1.13]; I2= 61%), NO2(HR, 1.03; 95% CI [1.00–1.07]; I2= 94%), and O3levels (HR, 1.01; 95% CI [0.91–1.11]; I2= 82%) was less clear, although a significant association could not be ruled out, and there was high heterogeneity across studies.DiscussionExisting evidence suggests a significant association between exposure to PM2·5and incidence of dementia and nonsignificant association between dementia and NOX, NO2, and O3exposure. However, results should be interpreted in light of the small number of studies and high heterogeneity of effects across studies.

Published
2021

44. Developments in NEW triad research

Author

Shawn N. Whitehead, Vladimir Hachinski, and Alexander Levit

Subjects
Aging, executive function, Blood-Brain Barrier, Brain, Cell Biology, blood-brain barrier, neurovascular unit, white matter, White Matter, dementia
Published
2022

45. Global Burden of Cardiovascular Diseases and Risk Factors, 1990–2019: Update From the GBD 2019 Study

Author

Roth, Gregory A, Mensah, George A, Johnson, Catherine O, Addolorato, Giovanni, Ammirati, Enrico, Baddour, Larry M, Barengo, Noël C, Beaton, Andrea Z, Benjamin, Emelia J, Benziger, Catherine P, Bonny, Aimé, Brauer, Michael, Brodmann, Marianne, Cahill, Thomas J, Carapetis, Jonathan, Catapano, Alberico L, Chugh, Sumeet S, Cooper, Leslie T, Coresh, Josef, Criqui, Michael, DeCleene, Nicole, Eagle, Kim A, Emmons-Bell, Sophia, Feigin, Valery L, Fernández-Solà, Joaquim, Fowkes, Gerry, Gakidou, Emmanuela, Grundy, Scott M, He, Feng J, Howard, George, Hu, Frank, Inker, Lesley, Karthikeyan, Ganesan, Kassebaum, Nicholas, Koroshetz, Walter, Lavie, Carl, Lloyd-Jones, Donald, Lu, Hong S, Mirijello, Antonio, Temesgen, Awoke Misganaw, Mokdad, Ali, Moran, Andrew E, Muntner, Paul, Narula, Jagat, Neal, Bruce, Ntsekhe, Mpiko, Moraes de Oliveira, Glaucia, Otto, Catherine, Owolabi, Mayowa, Pratt, Michael, Rajagopalan, Sanjay, Reitsma, Marissa, Ribeiro, Antonio Luiz P, Rigotti, Nancy, Rodgers, Anthony, Sable, Craig, Shakil, Saate, Sliwa-Hahnle, Karen, Stark, Benjamin, Sundström, Johan, Timpel, Patrick, Tleyjeh, Imad M, Valgimigli, Marco, Vos, Theo, Whelton, Paul K, Yacoub, Magdi, Zuhlke, Liesl, Murray, Christopher, Fuster, Valentin, GBD-NHLBI-JACC Global, Burden of, Cardiovascular Diseases, Writing Group, Gregory A, Roth George, A Mensah, Catherine O, Johnson, Giovanni, Addolorato, Enrico, Ammirati, Larry M, Baddour Noel, C Barengo, Andrea, Beaton, Emelia J, Benjamin Catherine, P Benziger, Aime, Bonny, Michael, Brauer, Marianne, Brodmann, Thomas J, Cahill Jonathan, R Carapetis, Alberico L, Catapano, Sumeet, Chugh, Leslie T, Cooper, Josef, Coresh, Michael H, Criqui Nicole, K DeCleene, Kim A, Eagle, Sophia, Emmons-Bell, Valery L, Feigin, Joaquim, Fernández-Sola, F Gerry, R Fowkes, Emmanuela, Gakidou, Scott M, Grundy Feng, J He, George, Howard, Frank, Hu, Lesley, Inker, Ganesan, Karthikeyan, Nicholas J, Kassebaum Walter, J Koroshetz, Carl, Lavie, Donald, Lloyd-Jones, Hong S, Antonio, Mirijello, Awoke T, Misganaw Ali, H Mokdad, Andrew E, Moran, Paul, Muntner, Jagat, Narula, Bruce, Neal, Mpiko, Ntsekhe, Gláucia M, M Oliveira, Catherine M, Otto Mayowa, O Owolabi, Michael, Pratt, Sanjay, Rajagopalan, Marissa B, Reitsma Antonio, Luiz P, Ribeiro Nancy, A Rigotti, Anthony, Rodgers, Craig A, Sable Saate, S Shakil, Karen, Sliwa, Benjamin A, Stark, Johan, Sundström, Patrick, Timpel, Imad I, Tleyjeh, Marco, Valgimigli, Theo, Vos, Paul K, Whelton, Magdi, Yacoub, Liesl J, Zuhlke, Mohsen, Abbasi-Kangevari, Alireza, Abdi, Aidin, Abedi, Victor, Aboyans, Woldu A, Abrha, Eman, Abu-Gharbieh, Abdelrahman I, Abushouk, Dilaram, Acharya, Tim, Adair, Oladimeji M, Adebayo, Zanfina, Ademi, Shailesh M, Advani, Khashayar, Afshari, Ashkan, Afshin, Gina, Agarwal, Pradyumna, Agasthi, Sohail, Ahmad, Sepideh, Ahmadi, Muktar B, Ahmed, Budi, Aji, Yonas, Akalu, Wuraola, Akande-Sholabi, Addis, Aklilu, Chisom J, Akunna, Fares, Alahdab, Ayman, Al-Eyadhy, Khalid F, Alhabib Sheikh, M Alif, Vahid, Alipour, Syed M, Aljunid, François, Alla, Amir, Almasi-Hashiani, Sami, Almustanyir, Rajaa M, Al-Raddadi Adeladza, K Amegah, Saeed, Amini, Arya, Aminorroaya, Hubert, Amu, Dickson A, Amugsi, Robert, Ancuceanu, Deanna, Anderlini, Tudorel, Andrei, Catalina Liliana, Andrei, Alireza, Ansari-Moghaddam, Zelalem A, Anteneh Ippazio, Cosimo Antonazzo, Benny, Antony, Razique, Anwer, Lambert T, Appiah, Jalal, Arabloo, Johan, Ärnlöv, Kurnia D, Artanti, Zerihun, Ataro, Marcel, Ausloos, Leticia, Avila-Burgos, Asma T, Awan Mamaru, A Awoke, Henok T, Ayele Muluken, A Ayza, Samad, Azari, Darshan B, B, Nafiseh, Baheiraei, Atif A, Baig, Ahad, Bakhtiari, Maciej, Banach, Palash C, Banik Emerson, A Baptista, Miguel A, Barboza, Lingkan, Barua, Sanjay, Basu, Neeraj, Bedi, Yannick, Béjot, Derrick A, Bennett Isabela, M Bensenor, Adam E, Berman Yihienew, M Bezabih, Akshaya S, Bhagavathula, Sonu, Bhaskar, Krittika, Bhattacharyya, Ali, Bijani, Boris, Bikbov, Mulugeta M, Birhanu, Archith, Boloor, Luisa C, Brant, Hermann, Brenner, Nikolay I, Briko Zahid, A Butt, Florentino Luciano, Caetano Dos, Santos Leah, E Cahill, Lucero, Cahuana-Hurtado, Luis A, Cámera Ismael, R Campos-Nonato, Carlos, Cantu-Brito, Josip, Car, Juan J, Carrero, Felix, Carvalho, Carlos A, Castañeda-Orjuela, Ferrán, Catalá-López, Ester, Cerin, Jaykaran, Charan, Vijay Kumar, Chattu, Simiao, Chen, Ken L, Chin Jee-Young, J Choi, Dinh-Toi, Chu, Sheng-Chia, Chung, Cirillo, Massimo, Sean, Coffey, Sara, Conti, Vera M, Costa David, K Cundiff, Omid, Dadras, Baye, Dagnew, Xiaochen, Dai, Albertino A, M Damasceno, Lalit, Dandona, Rakhi, Dandona, Kairat, Davletov, Vanessa De, la Cruz-Góngora, Fernando P, De la, Hoz Jan-Walter, De Neve, Edgar, Denova-Gutiérrez, Meseret Derbew, Molla Behailu, T Derseh, Rupak, Desai, Günther, Deuschl, Samath D, Dharmaratne, Meghnath, Dhimal, Raja Ram, Dhungana, Mostafa, Dianatinasab, Daniel, Diaz, Shirin, Djalalinia, Klara, Dokova, Abdel, Douiri, Bruce B, Duncan Andre, R Duraes, Arielle W, Eagan, Sanam, Ebtehaj, Aziz, Eftekhari, Sahar, Eftekharzadeh, Michael, Ekholuenetale, Nevine El, Nahas Islam, Y Elgendy, Muhammed, Elhadi, Shaimaa I, El-Jaafary, Sadaf, Esteghamati, Atkilt E, Etisso, Oghenowede, Eyawo, Ibtihal, Fadhil, Emerito Jose, A Faraon, Pawan S, Faris, Medhat, Farwati, Farshad, Farzadfar, Eduarda, Fernandes, Carlota Fernandez, Prendes, Pietro, Ferrara, Irina, Filip, Florian, Fischer, David, Flood, Takeshi, Fukumoto, Mohamed M, Gad, Shilpa, Gaidhane, Morsaleh, Ganji, Jalaj, Garg, Abadi K, Gebre Birhan, G Gebregiorgis, Kidane Z, Gebregzabiher Gebreamlak, G Gebremeskel, Lemma, Getacher, Abera Getachew, Obsa, Alireza, Ghajar, Ahmad, Ghashghaee, Nermin, Ghith, Simona, Giampaoli, Syed Amir, Gilani Paramjit, S Gill, Richard F, Gillum Ekaterina, V Glushkova, Elena V, Gnedovskaya, Mahaveer, Golechha, Kebebe B, Gonfa Amir, Hossein Goudarzian, Alessandra C, Goulart Jenny, S Guadamuz, Avirup, Guha, Yuming, Guo, Rajeev, Gupta, Vladimir, Hachinski, Nima, Hafezi-Nejad, Teklehaimanot G, Haile Randah, R Hamadeh, Samer, Hamidi, Graeme J, Hankey, Arief, Hargono, Risky K, Hartono, Maryam, Hashemian, Abdiwahab, Hashi, Shoaib, Hassan, Hamid Y, Hassen Rasmus, J Havmoeller, Simon I, Hay, Khezar, Hayat, Golnaz, Heidari, Claudiu, Herteliu, Ramesh, Holla, Mostafa, Hosseini, Mehdi, Hosseinzadeh, Mihaela, Hostiuc, Sorin, Hostiuc, Mowafa, Househ, Junjie, Huang, Ayesha, Humayun, Ivo, Iavicoli, Charles U, Ibeneme Segun, E Ibitoye, Olayinka S, Ilesanmi Irena, M Ilic, Milena D, Ilic, Usman, Iqbal, Seyed Sina, N Irvani, Sheikh Mohammed, Shariful Islam, Rakibul M, Islam, Hiroyasu, Iso, Masao, Iwagami, Vardhmaan, Jain, Tahereh, Javaheri, Sathish Kumar, Jayapal, Shubha, Jayaram, Ranil, Jayawardena, Panniyammakal, Jeemon, Ravi P, Jha Jost, B Jonas, Jitendra, Jonnagaddala, Farahnaz, Joukar, Jacek J, Jozwiak, Mikk, Jürisson, Ali, Kabir, Tanvir, Kahlon, Rizwan, Kalani, Rohollah, Kalhor, Ashwin, Kamath, Ibrahim, Kamel, Himal, Kandel, Amit, Kandel, André, Karch, Ayele Semachew, Kasa Patrick, D M, C Katoto, Gbenga A, Kayode Yousef, S Khader, Mohammad, Khammarnia, Muhammad S, Khan Md, Nuruzzaman Khan, Maseer, Khan, Ejaz A, Khan, Khaled, Khatab, Gulam M, A Kibria, Yun Jin, Kim Gyu, Ri Kim, Ruth W, Kimokoti, Sezer, Kisa, Adnan, Kisa, Mika, Kivimäki, Dhaval, Kolte, Ali, Koolivand, Vladimir A, Korshunov Sindhura, Lakshmi Koulmane, Laxminarayana, Ai, Koyanagi, Kewal, Krishan, Vijay, Krishnamoorthy, Barthelemy Kuate, Defo Burcu, Kucuk Bicer, Vaman, Kulkarni, G Anil, Kumar, Nithin, Kumar, Om P, Kurmi, Dian, Kusuma, Gene F, Kwan Carlo, La Vecchia, Ben, Lacey, Tea, Lallukka, Qing, Lan, Savita, Lasrado, Zohra S, Lassi, Paolo, Lauriola, Wayne R, Lawrence, Avula, Laxmaiah, Kate E, LeGrand, Ming-Chieh, Li, Bingyu, Li, Shanshan, Li, Stephen S, Lim, Lee-Ling, Lim, Hualiang, Lin, Ziqiang, Lin, Ro-Ting, Lin, Xuefeng, Liu, Alan D, Lopez, Stefan, Lorkowski, Paulo A, Lotufo, Alessandra, Lugo, Nirmal K, M, Fabiana, Madotto, Morteza, Mahmoudi, Azeem, Majeed, Reza, Malekzadeh, Ahmad A, Malik Abdullah, A Mamun, Navid, Manafi, Mohammad Ali, Mansournia Lorenzo, G Mantovani, Santi, Martini, Manu R, Mathur, Giampiero, Mazzaglia, Suresh, Mehata, Man Mohan, Mehndiratta, Toni, Meier, Ritesh G, Menezes, Atte, Meretoja, Tomislav, Mestrovic, Bartosz, Miazgowski, Tomasz, Miazgowski, Irmina Maria, Michalek Ted, R Miller, Erkin M, Mirrakhimov, Hamed, Mirzaei, Babak, Moazen, Masoud, Moghadaszadeh, Yousef, Mohammad, Dara K, Mohammad, Shafiu, Mohammed, Mohammed A, Mohammed, Yaser, Mokhayeri, Mariam, Molokhia, Ahmed A, Montasir, Ghobad, Moradi, Rahmatollah, Moradzadeh, Paula, Moraga, Lidia, Morawska, Ilais Moreno, Velásquez, Jakub, Morze, Sumaira, Mubarik, Walter, Muruet, Kamarul Imran, Musa Ahamarshan, J Nagarajan, Mahdi, Nalini, Vinay, Nangia, Atta Abbas, Naqvi Sreenivas, Narasimha Swamy, Bruno R, Nascimento Vinod, C Nayak, Javad, Nazari, Milad, Nazarzadeh, Ruxandra I, Negoi Sandhya, Neupane Kandel, Huong L, T Nguyen, Molly R, Nixon, Bo, Norrving, Jean Jacques, Noubiap Brice, E Nouthe, Christoph, Nowak, Oluwakemi O, Odukoya Felix, A Ogbo, Andrew T, Olagunju, Hans, Orru, Alberto, Ortiz, Samuel M, Ostroff Jagadish, Rao Padubidri, Raffaele, Palladino, Adrian, Pana, Songhomitra, Panda-Jonas, Utsav, Parekh, Eun-Cheol, Park, Mojtaba, Parvizi, Fatemeh Pashazadeh, Kan Urvish, K Patel, Mona, Pathak, Rajan, Paudel, Veincent Christian, F Pepito, Arokiasamy, Perianayagam, Norberto, Perico, Hai Q, Pham, Thomas, Pilgrim, Michael A, Piradov, Farhad, Pishgar, Vivek, Podder, Roman V, Polibin, Akram, Pourshams, Dimas R, A Pribadi, Navid, Rabiee, Mohammad, Rabiee, Amir, Radfar, Alireza, Rafiei, Fakher, Rahim, Vafa, Rahimi-Movaghar, Mohammad Hifz, Ur Rahman, Muhammad Aziz, Rahman Amir, Masoud Rahmani, Ivo, Rakovac, Pradhum, Ram, Sudha, Ramalingam, Juwel, Rana, Priyanga, Ranasinghe, Sowmya J, Rao, Priya, Rathi, Lal, Rawal, Wasiq F, Rawasia, Reza, Rawassizadeh, Giuseppe, Remuzzi, Andre M, N Renzaho, Aziz, Rezapour, Seyed Mohammad, Riahi Ross, L Roberts-Thomson, Leonardo, Roever, Peter, Rohloff, Michele, Romoli, Gholamreza, Roshandel, Godfrey M, Rwegerera, Seyedmohammad, Saadatagah, Maha M, Saber-Ayad, Siamak, Sabour, Simona, Sacco, Masoumeh, Sadeghi, Sahar Saeedi, Moghaddam, Saeed, Safari, Amirhossein, Sahebkar, Sana, Salehi, Hamideh, Salimzadeh, Mehrnoosh, Samaei, Abdallah M, Samy Itamar, S Santos, Milena M, Santric-Milicevic, Nizal, Sarrafzadegan, Arash, Sarveazad, Thirunavukkarasu, Sathish, Monika, Sawhney, Mete, Saylan, Maria I, Schmidt Aletta, E Schutte, Subramanian, Senthilkumaran, Sadaf G, Sepanlou, Feng, Sha, Saeed, Shahabi, Izza, Shahid, Masood A, Shaikh, Mahdi, Shamali, Morteza, Shamsizadeh, Md Shajedur, Rahman Shawon, Aziz, Sheikh, Mika, Shigematsu, Min-Jeong, Shin, Jae Il, Shin, Rahman, Shiri, Ivy, Shiue, Kerem, Shuval, Soraya, Siabani, Tariq J, Siddiqi Diego, A S, Silva Jasvinder, A Singh, Ambrish Singh, Mtech Valentin, Y Skryabin, Anna A, Skryabina, Amin, Soheili, Emma E, Spurlock, Leo, Stockfelt, Stefan, Stortecky, Saverio, Stranges, Rizwan Suliankatchi, Abdulkader, 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Yatsuya, Tomas Y, Yeheyis, Yigizie, Yeshaw, Christopher S, Yilgwan, Naohiro, Yonemoto, Chuanhua, Yu, Hasan, Yusefzadeh, Geevar, Zachariah, Sojib Bin, Zaman Muhammed, S Zaman, Maryam, Zamanian, Ramin, Zand, Alireza, Zandifar, Afshin, Zarghi, Mikhail S, Zastrozhin, Anasthasia, Zastrozhina, Zhi-Jiang, Zhang, Yunquan, Zhang, Wangjian, Zhang, Chenwen, Zhong, Zhiyong, Zou, Yves Miel, H Zuniga, Christopher J, L Murray, Valentin, Fuster, Roth, G, Mensah, G, Johnson, C, Addolorato, G, Ammirati, E, Baddour, L, Barengo, N, Beaton, A, Benjamin, E, Benziger, C, Bonny, A, Brauer, M, Brodmann, M, Cahill, T, Carapetis, J, Catapano, A, Chugh, S, Cooper, L, Coresh, J, Criqui, M, Decleene, N, Eagle, K, Emmons-Bell, S, Feigin, V, Fernandez-Sola, J, Fowkes, G, Gakidou, E, Grundy, S, He, F, Howard, G, Hu, F, Inker, L, Karthikeyan, G, Kassebaum, N, Koroshetz, W, Lavie, C, Lloyd-Jones, D, Lu, H, Mirijello, A, Temesgen, A, Mokdad, A, Moran, A, Muntner, P, Narula, J, Neal, B, Ntsekhe, M, Moraes de Oliveira, G, 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Wubishet, Gelin, Xu, Ali, Yadollahpour, Kazumasa, Yamagishi, Lijing, L, Yan, Srikanth, Yandrapalli, Yuichiro, Yano, Hiroshi, Yatsuya, Tomas, Y, Yeheyis, Yigizie, Yeshaw, Christopher, S, Yilgwan, Naohiro, Yonemoto, Chuanhua, Yu, Hasan, Yusefzadeh, Geevar, Zachariah, Sojib, Bin, Zaman, Muhammed, Maryam, Zamanian, Ramin, Zand, Alireza, Zandifar, Afshin, Zarghi, Mikhail, S, Zastrozhin, Anasthasia, Zastrozhina, Zhi-Jiang, Zhang, Yunquan, Zhang, Wangjian, Zhang, Chenwen, Zhong, Zhiyong, Zou, Yves, Miel, Zuniga, H, Christopher, J, Murray, L, and Valentin, Fuster

Subjects
cardiovascular disease, global health, health policy, population health
Abstract

Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability. This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019. GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019. Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019. The global trends for disability-adjusted life years (DALYs) and years of life lost also increased significantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period. The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019. The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019. Cardiovascular diseases remain the leading cause of disease burden in the world. CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high-income countries. There is an urgent need to focus on implementing existing cost-effective policies and interventions if the world is to meet the targets for Sustainable Development Goal 3 and achieve a 30% reduction in premature mortality due to noncommunicable diseases.

Published
2020

46. The Ambibaric Brain:Pathophysiological and Clinical Implications

Author

Vladimir Hachinski and Leif Østergaard

Subjects
brain, perfusion, 03 medical and health sciences, 0302 clinical medicine, Animals, Humans, Medicine, Cerebral Hemorrhage, 030304 developmental biology, Advanced and Specialized Nursing, 0303 health sciences, Amyloid beta-Peptides, business.industry, Brain, blood pressure, cerebral blood volume, Pathophysiology, Blood pressure, Cerebral blood volume, Cerebrovascular Circulation, Hypertension, basal ganglia, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Neuroscience, 030217 neurology & neurosurgery
Abstract

We propose a new evolutionary interpretation of the brain’s circulation that has physiological, pathophysiological, and clinical implications. We review the evidence for the concept, discuss clinical implications, and suggest techniques to address outstanding questions. We conclude that the brain circulation contains complementary low-pressure and high-pressure system that must be kept in balance for optimal brain health.

Published
2021

47. A new definition of brain health

Author

Shahram Oveisgharan, Jason A. Gilliland, Abolfazl Avan, and Vladimir Hachinski

Subjects
Ontario, medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), business.industry, Incidence (epidemiology), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Health Status, Incidence, MEDLINE, Brain, Mental health, Stroke, Mental Health, medicine, Humans, Neurology (clinical), Intensive care medicine, business
Published
2021

48. John W. Norris

Author

Vladimir Hachinski, Natan M. Bornstein, and Hugh S. Markus

Subjects
Advanced and Specialized Nursing, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), MEDLINE, medicine.disease, Virology, Pneumonia, Pandemic, medicine, Neurology (clinical), Cardiology and Cardiovascular Medicine, business
Published
2020

49. IN MEMORIAM JOHN W NORRIS (1933–2020)

Author

Hugh S. Markus, Vladimir Hachinski, and Natan M. Bornstein

Subjects
Neurology, business.industry, In Memoriam, MEDLINE, Medicine, Neurology (clinical), business, Cardiology and Cardiovascular Medicine, Classics
Published
2020

50. Impaired behavioural flexibility related to white matter microgliosis in the TgAPP21 rat model of Alzheimer disease

Author

Olivia Hough, Aaron M. Regis, Shawn N. Whitehead, Cansu Agca, Brian L. Allman, Alexander Levit, Vladimir Hachinski, Andrew Gibson, Shikhar Maheshwari, and Yuksel Agca

Subjects
Male, 0301 basic medicine, Neuroimmunomodulation, Immunology, Morris water navigation task, Plaque, Amyloid, Corpus callosum, law.invention, White matter, Amyloid beta-Protein Precursor, Executive Function, 03 medical and health sciences, Behavioral Neuroscience, Cognition, 0302 clinical medicine, Operant conditioning chamber, Alzheimer Disease, law, medicine, Animals, Maze Learning, Endocrine and Autonomic Systems, business.industry, Cognitive flexibility, Brain, medicine.disease, Executive functions, White Matter, Rats, Inbred F344, Rats, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, Conditioning, Operant, Microglia, Rats, Transgenic, Alzheimer's disease, business, Neuroscience, 030217 neurology & neurosurgery, Executive dysfunction
Abstract

Executive dysfunction and white matter inflammation continue to be relatively understudied in rodent models of Alzheimer’s disease (AD). Behavioural inflexibility is an important component of executive dysfunction that can be further categorized as perseverative or regressive, which respectively specify whether maladaptive persistence occurs early or late during a behavioural change. Previous studies of the TgAPP21 rat model of AD (expressing pathogenic hAPP) suggested a potentially spontaneous increase of regressive behavioral inflexibility. In this study, 7–8-month-old male TgAPP21 rats were tested for behavioral flexibility, learning, and memory using an operant conditioning chamber and the Morris Water Maze (MWM). TgAPP21 rats demonstrated a regressive behavioral inflexibility during set shifting in an operant conditioning chamber (regressive errors η2 = 0.32 and number of errors after criterion η2 = 0.33). Regressive behavior was also demonstrated in the MWM probe test, wherein TgAPP21 rats significantly increased their swim time in the target quadrant during the last third of the probe test (43% vs 33% in the first 2 thirds of the probe test or the Wt rats’ 29%–32%); this behavioral phenotype has not been previously described in the MWM. TgAPP21 demonstrated further impairment of behavioural inflexibility as they committed a greater number of reversal errors in the operant conditioning chamber (η2 = 0.30). Diffuse microglia activation was increased in the white matter tracts of TgAPP21 (corpus callosum, cingulum, and internal capsule; η2 = 0.59–0.62), which was found to correlate with the number of reversal errors in the operant conditioning chamber (R2 = 0.42). As TgAPP21 rats do not spontaneously develop amyloid plaques but have been shown in previous studies to be vulnerable to the development of plaques, these rats demonstrate an important onset of cognitive change and inflammation in the pre-plaque phase of AD. TgAPP21 rats are also an instrumental model for studying the role and mechanism of white matter microglial activation in executive functioning. This is pertinent to clinical research of prodromal AD which has suggested that white matter inflammation may underlie impairment of executive functions such as behavioral flexibility.

Published
2019

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