Stroke Medicine Research Articles

Is the TOAST Classification Suitable for Use in Personalized Medicine in Ischemic Stroke?

Pathophysiologic classification of ischemic stroke is essential to a personalized approach to stroke treatment. The Trial of Org 101072 in Acute Stroke Treatment (TOAST) classification is the most frequently used tool to classify index ischemic strokes. We aimed to assess presence of small and large vessel disease markers across the TOAST groups. In an observational study, 99 ischemic stroke patients were consecutively included and classified according to TOAST. The assessment was supplemented with cerebral small vessel disease (SVD) score, based on Magnetic Resonance Imaging (MRI), and tests for carotid atherosclerosis, ankle–brachial index (ABI), estimated glomerular filtration rate (eGFR), and peripheral reactive hyperemia index (RHI). Markers of small and large vessel disease were present in all TOAST groups. Carotid stenosis and atrial fibrillation were associated with their respective TOAST groups (p = 0.023 and p < 0.001, respectively). We found no association between the SVD score and the small vessel occlusion TOAST group (p = 0.59), and carotid atherosclerosis (p = 0.35), RHI (p = 0.39), ABI (p = 0.20), and eGFR (p = 0.79) were not associated with TOAST groups. The TOAST classification does not provide differential information on the pathophysiologies of the ischemic stroke. An operational classification that contains quantification of each vascular pathophysiology in the individual patient is pivotal for future research and development of personalized medicine.

Development of a Core Outcome Set in the Clinical Trials of Traditional Chinese Medicine for Stroke: A Study Protocol.

IntroductionStroke, an acute cerebrovascular disease, is mainly caused by the sudden rupture or occlusion of blood vessels, and is subdivided into ischemic stroke and hemorrhagic stroke. It has become the second leading cause of death worldwide. In Chinese clinical practice, traditional Chinese medicine (TCM)/Integrative Medicine has been widely used for the treatment of stroke. Numerous randomized controlled trials (RCTs) of TCM/Integrative Medicine for stroke have been conducted to improve the efficacy and safety outcomes. However, their conclusions should be treated with caution because of the methodological quality defects in the clinical research. Pervasive inconsistencies are present in the outcomes collected and reported across these studies, which may lead to the pooling of discrepant data and preclude meta-analysis. The issue could be addressed by developing a core outcome set (COS).AimThe aim of this study is to develop a COS in the clinical trials of TCM/Integrative Medicine in the treatment of stroke.Method and AnalysisA steering group will be set up to organize and guide the development of the COS. The study contains three phases: (I) development of an initial outcome list covering all relevant outcomes, via two steps: (i) systematic reviews of outcomes for clinical trials of TCM/ Integrative Medicine for stroke; (ii) semi-structured interviews with patients suffering from stroke; (II) conduction of three round of Delphi surveys with different stakeholder groups to prioritize important outcomes; (III) integration of outcomes into a core outcome set by a consensus meeting.Ethics and DisseminationThis study has been granted by the Ethics Committee of Tianjin University of Traditional Chinese Medicine (TJUTCM-EC20210003). When the COS is completed, we will publish it in an appropriate journal to promote further widespread use.RegistrationThis study has been registered at the Core Outcome Measures in Effectiveness Trials initiative, COMET database (Registration #1678).

Abstract TP76: The Impact Of Registries In Stroke Literature

Introduction: Registries represent a main source of data to the advances in medical literature. In stroke medicine, they serve as key points of discussion and elaboration for future clinical trials, as well as evaluation tools for several treatment modalities in different patient populations. We performed an analysis of recent stroke registries to evaluate their impact in literature. Methods: We performed PubMed and Google Scholar search using keywords with Boolean operators to identify studies deriving from stroke registries between January 2000 and June 2021. All registries identified were further characterized regarding study design, sample size, number of centers, number of peer reviewed articles or conference abstracts originating from it, with their respective number of citations and impact factor of journals. Results: A total of 51 registries were identified, comprising 43584 patients. Forty-three (84.3%) were prospective. Forty-five (88.2%) were multicenter. Sixteen (31.4%) focused in a specific device for mechanical thrombectomy. Twenty-seven (52.9%) were registered on clinicaltrials.gov. The most participating countries were United States in 16 (31.4%) and Germany in 8 (15.7%). Twenty-seven (52.9%) registries originated a total of 295 peer-reviewed articles, 6841 citations and a sum of impact factors of 1282.8. The median impact factor of journals publishing articles from registries was 5.51 (interquartile range, 3.27-7.91). The median number of citations per article was 13 (interquartile range, 4-37). Between registered and unregistered registries, there was no significant difference in the median number of publications (P=0.08), citations (P=0.158) or impact factor (P=0.124). Between registries specific and unspecific to a certain device, there was no significant difference in median number of publications (P=1.67), citations (P=0.631) or impact factor (P=0.509). Conclusions: Stroke registries provide a meaningful data source for literature regardless of registration or specificity to a certain device, and represent a key mechanism in the advances of stroke care. Contribution to stroke registries are key mechanism to elucidate clinical questions that require large sample size and should be incentivized.

Abstract WP83: The Challenges Of Stroke Prevention Following Intracerebral Haemorrhage; A Qualitative Study Exploring Physicians’ Decision Making.

Introduction: Initiating long-term oral anticoagulation (OAC) therapy in intracerebral haemorrhage (ICH) survivors who have atrial fibrillation (AF) has clinical equipoise for stroke physicians internationally, given the lack of clinical trial evidence. Understanding how physicians make decisions about stroke prevention in these patients will support and improve current decision-making practice and inform future guidelines. Aim: To explore physicians’ decision-making around prescription of long-term OAC for stroke prevention in patients with AF following an ICH. Methods: Qualitative sub-study of the PREvention of STroke in Intracerebral haemorrhaGE survivors with Atrial Fibrillation (PRESTIGE-AF) trial [NCT NCT03996772]. Semi-structured interviews with data analysed using Framework analysis. Results: Twenty stroke physicians (women n = 6 (30%), consultant in stroke medicine n =10, head of stroke department n = 6, geriatrician working in stroke n = 2, residents in neurology n = 2) across five European countries (Spain, France, Germany, Austria, UK) participated. The overarching theme ‘Managing Uncertainty’ highlights the difficulties faced by physicians. It draws together three sub-themes: ‘Computing the risks’, focusing on how physicians weigh-up the risks and benefits of long-term OAC; ‘The patient perspective’, which considers patients’ experiences and preferences; ‘Making the decision together’, which focuses on issues of communication between physicians and patients. Conclusion: The need to balance risks/benefits in the absence of data from randomised controlled trials and the uncertainty surrounding long-term outcomes of OAC were key challenges for physicians. Physicians rely on past personal clinical experience and collegiate advice to aid decision making. Physicians strive to ensure that patients understand the decision-making process. Future practice should support physicians in communicating clinical uncertainty to patients and encourage patients and physicians to work together to understand individual patients’ needs. Funding: This project has received funding from the European Union’s Horizon 2020 research and innovation programme under Grant Agreement No. 754517.

Interpretable CNN for ischemic stroke subtype classification with active model adaptation

BackgroundTOAST subtype classification is important for diagnosis and research of ischemic stroke. Limited by experience of neurologist and time-consuming manual adjudication, it is a big challenge to finish TOAST classification effectively. We propose a novel active deep learning architecture to classify TOAST.MethodsTo simulate the diagnosis process of neurologists, we drop the valueless features by XGB algorithm and rank the remaining ones. Utilizing active learning framework, we propose a novel causal CNN, in which it combines with a mixed active selection criterion to optimize the uncertainty of samples adaptively. Meanwhile, KL-focal loss derived from the enhancement of Focal loss by KL regularization is introduced to accelerate the iterative fine-tuning of the model.ResultsTo evaluate the proposed method, we construct a dataset which consists of totally 2310 patients. In a series of sequential experiments, we verify the effectiveness of each contribution by different evaluation metrics. Experimental results show that the proposed method achieves competitive results on each evaluation metric. In this task, the improvement of AUC is the most obvious, reaching 77.4.ConclusionsWe construct a backbone causal CNN to simulate the neurologist process of that could enhance the internal interpretability. The research on clinical data also indicates the potential application value of this model in stroke medicine. Future work we would consider various data types and more comprehensive patient types to achieve fully automated subtype classification.

Neurologists in stroke medicine

Neurologists in stroke medicine

Influence of the coronavirus disease 2019 (COVID-19) pandemic on the incidence of heat stroke and heat exhaustion in Japan: a nationwide observational study based on the Heatstroke STUDY 2019 (without COVID-19) and 2020 (with COVID-19).

AimTo assess heat stroke and heat exhaustion occurrence and response during the coronavirus disease 2019 pandemic in Japan.MethodsThis retrospective, multicenter, registry‐based study describes and compares the characteristics of patients between the months of July and September in 2019 and 2020. Factors affecting heat stroke and heat exhaustion were statistically analyzed. Cramér’s V was calculated to determine the effect size for group comparisons. We also investigated the prevalence of mask wearing and details of different cooling methods.ResultsNo significant differences were observed between 2019 and 2020. In both years, in‐hospital mortality rates just exceeded 8%. Individuals >65 years old comprised 50% of cases and non‐exertional onset (office work and everyday life) comprised 60%–70%, respectively. The recommendations from the Working Group on Heat Stroke Medicine given during the coronavirus disease pandemic in 2019 had a significant impact on the choice of cooling methods. The percentage of cases, for which intravascular temperature management was performed and cooling blankets were used increased, whereas the percentage of cases in which evaporative plus convective cooling was performed decreased. A total of 49 cases of heat stroke in mask wearing were reported.ConclusionEpidemiological assessments of heat stroke and heat exhaustion did not reveal significant changes between 2019 and 2020. The findings suggest that awareness campaigns regarding heat stroke prevention among the elderly in daily life should be continued in the coronavirus disease 2019 pandemic. In the future, it is also necessary to validate the recommendations of the Working Group on Heatstroke Medicine.

Diagnostic and prognostic utility of brain collaterals in acute ischaemic stroke: Current knowledge and insights on treatment decision-making

Stroke is a leading cause of death and disability worldwide. The advent of acute reperfusion therapy, intravenous thrombolysis and endovascular thrombectomy, has revolutionized the field of stroke medicine, and neurology in general. Recent studies have implicated a major role of cerebral collaterals in the trajectory of acute ischemic stroke patients receiving reperfusion therapy. Collaterals sustain blood supply to the tissue in the setting of acute ischemia which prevents further expansion of the hypo perfused tissue, playing an important role in determining outcomes after acute ischemic stroke. The use of collateral assessment in routine practice in acute ischemic stroke, let alone in reperfusion therapy, is far from universal and limited. Future work in embedding collateral assessment in standards of care in acute stroke and management is warranted. This article provides a comprehensive update on the diagnostic and prognostic utility of collaterals in acute ischemic stroke and recommendations on collateral-based decision making in acute stroke and steps that can be taken for its rapid uptake in clinical practice.

Precision medicine in stroke: towards personalized outcome predictions using artificial intelligence.

Stroke ranks among the leading causes for morbidity and mortality worldwide. New and continuously improving treatment options such as thrombolysis and thrombectomy have revolutionized acute stroke treatment in recent years. Following modern rhythms, the next revolution might well be the strategic use of the steadily increasing amounts of patient-related data for generating models enabling individualized outcome predictions. Milestones have already been achieved in several health care domains, as big data and artificial intelligence have entered everyday life.The aim of this review is to synoptically illustrate and discuss how artificial intelligence approaches may help to compute single-patient predictions in stroke outcome research in the acute, subacute and chronic stage. We will present approaches considering demographic, clinical and electrophysiological data, as well as data originating from various imaging modalities and combinations thereof. We will outline their advantages, disadvantages, their potential pitfalls and the promises they hold with a special focus on a clinical audience. Throughout the review we will highlight methodological aspects of novel machine-learning approaches as they are particularly crucial to realize precision medicine. We will finally provide an outlook on how artificial intelligence approaches might contribute to enhancing favourable outcomes after stroke.

Cerebral microbleeds and stroke: more questions than answers

With the widespread availability of MRI scanning, cerebral microbleeds (CMBs) are being increasingly recognised in patients with stroke and in healthy individuals. As CMBs are commonly viewed as markers of increased risk of intracerebral haemorrhage (ICH), there are concerns regarding the use of antithrombotic agents (antiplatelets, and especially anticoagulants) in the presence of CMBs, even in patients at high risk of ischaemic events. The use of antiplatelet or anticoagulant therapy in the presence of CMBs, balancing the risk of recurrent ischaemic stroke against the risk of possible intracranial bleeding, is one of the most contentious contemporary issues in stroke medicine.

254 OPTIMISING COMMUNICATION WITH FAMILIES OF PATIENTS ON ACUTE STROKE AND GERIATRIC MEDICINE WARDS IN A LARGE TERTIARY HOSPITAL

Abstract Background Good communication with patients and families is important for older adults admitted to acute stroke or geriatric medicine wards, particularly with COVID19-related restricted visiting. These patients often have communication difficulties including aphasia, delirium, cognitive or hearing impairment, limiting their own communication with relatives. Using the Plan, Do, Study, Act (PDSA) approach we undertook a quality improvement project to optimise communication with families of patients on above wards in a large tertiary hospital. Methods PDSA cycle 1: Staff were surveyed to identify satisfaction level with communication and ways to optimise communication. Inpatients on study wards were identified, we recorded demographic and clinical details and prevalence of communication difficulties. We created a designated folder with individual ‘communication sheets’ in conjunction with ward doctors and the nurse manager. PDSA cycle 2: We performed a rapid interval audit of the communication folder use. ‘Outlier’ patients were excluded as their teams did not receive education about folder use. Results PDSA cycle 1: A total of 90 inpatients on three wards were included, mean age 78y (SD ±14.4y), 47% were male. Three-quarters (73%) had a communication difficulty noted, reported by nursing staff. Two patients were intubated and six had stroke-related aphasia. Half of surveyed staff reported communication with families was suboptimal. Most (86%) suggested a centrally-located communication logbook would be helpful. PDSA cycle 2: Over two weeks, communication sheets were reviewed for all included patients. Median frequency of calls to families was 4 days (range 0–14). Most (79%) had the name of the primary contact clearly documented. Many (52%) included no contact number. Only 9% had secondary contact information documented. Conclusion Communication with families of patients on acute stroke and geriatric medicine wards was suboptimal. Over a short interval this improved with regular phone calls using specific centrally-located communication folders. Further optimisation of their use is needed.

박태기나무 씨 에탄올 추출물의 아세틸콜린에스테라제 억제 활성과 항아밀로이드 효과

Background: The root and bark of Cercis chinensis Bunge have been used as Chinese herbal medicines for stroke, hypertension, and gynecological diseases. The seed of C. chinensis is classified as a food ingredient in the Food Public Code. In this study, the inhibitory activities of Cercis chinensis Bunge seed against beta-amyloid (Aβ) secretion and acetylcholinesterase (AChE) were investigated.<BR>Methods and Results: The effect of 50% ethanolic extract of C. chinensis Bunge seed (CCS) on Aβ secretion in APPswe cells was analyzed by Aβ enzyme-linked immunosorbent assay (ELISA). CCS dose-dependently decreased Aβ1-42 secretion at 50 and 100 ㎍/㎖. The half-maximal inhibitory concentration (IC50) values of CCS were 45.02 ㎍/㎖ in Aβ1-40 and 43.48 ㎍/㎖ in Aβ1-42. To analyze the metabolism of amyloid precursor protein (APP) via β-secretase, the beta-carboxyl-terminal fragment (β-CTF) level was measured via ELISA and was found to be dose-dependently increased upon CSS treatment. Additionally, western blot analysis was performed to check the protein expression level of APP, soluble alpha (sAPPα), and CTF. The APP protein level did not change upon CCS treatment but sAPPα secretion level increased, indicating a tendency to increase both α- and β-CTF. These results suggest that CCS reduces Aβ secretion by targeting γ-secretase. Additionally, CCS showed a strong AChE inhibitory activity at an IC50 value of 8.37 ㎍/㎖.<BR>Conclusions: CCS exhibited Aβ reduction via γ-secretase and AChE inhibition and may be used as a material to develop healthy functional foods and medicine for Alzheimer

Imaging Acute Stroke: From One-Size-Fit-All to Biomarkers.

In acute stroke management, time window has been rigidly used as a guide for decades and the reperfusion treatment is only available in the first few limited hours. Recently, imaging-based selection of patients has successfully expanded the treatment window out to 16 and even 24 h in the DEFUSE 3 and DAWN trials, respectively. Recent guidelines recommend the use of imaging techniques to guide therapeutic decision-making and expanded eligibility in acute ischemic stroke. A tissue window is proposed to replace the time window and serve as the surrogate marker for potentially salvageable tissue. This article reviews the evolution of time window, addresses the advantage of a tissue window in precision medicine for ischemic stroke, and discusses both the established and emerging techniques of neuroimaging and their roles in defining a tissue window. We also emphasize the metabolic imaging and molecular imaging of brain pathophysiology, and highlight its potential in patient selection and treatment response prediction in ischemic stroke.

Stroke in Africa: profile, progress, prospects and priorities.

Stroke is a leading cause of disability, dementia and death worldwide. Approximately 70% of deaths from stroke and 87% of stroke-related disability occur in low-income and middle-income countries. At the turn of the century, the most common diseases in Africa were communicable diseases, whereas non-communicable diseases, including stroke, were considered rare, particularly in sub-Saharan Africa. However, evidence indicates that, today, Africa could have up to 2–3-fold greater rates of stroke incidence and higher stroke prevalence than western Europe and the USA. In Africa, data published within the past decade show that stroke has an annual incidence rate of up to 316 per 100,000, a prevalence of up to 1,460 per 100,000 and a 3-year fatality rate greater than 80%. Moreover, many Africans have a stroke within the fourth to sixth decades of life, with serious implications for the individual, their family and society. This age profile is particularly important as strokes in younger people tend to result in a greater loss of self-worth and socioeconomic productivity than in older individuals. Emerging insights from research into stroke epidemiology, genetics, prevention, care and outcomes offer great prospects for tackling the growing burden of stroke on the continent. In this article, we review the unique profile of stroke in Africa and summarize current knowledge on stroke epidemiology, genetics, prevention, acute care, rehabilitation, outcomes, cost of care and awareness. We also discuss knowledge gaps, emerging priorities and future directions of stroke medicine for the more than 1 billion people who live in Africa.

The neuroprotective effect of pretreatment with carbon dots from Crinis Carbonisatus (carbonized human hair) against cerebral ischemia reperfusion injury

BackgroundCerebral infarction and cerebral hemorrhage, also known as “stroke”, is one of the leading cause of death. At present, there is no real specific medicine for stroke. Crinis Carbonisatus (named Xue-yu-tan in Chinese), produced from carbonized hair of healthy human, and has been widely applied to relieve pain and treat epilepsy, stroke and other diseases in China for thousands of years.ResultsIn this work, a new species of carbon dots derived from Crinis Carbonisatus (CrCi-CDs) were separated and identified. And the neuroprotective effect of carbon dots from CrCi were evaluated using the middle cerebral artery occlusion (MCAO) model. Neurological deficit score and infarction volume was assessed, evans blue content of ischemic hemispheres was measured, the concentrations of inflammatory factors, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) in the cortex were measured, and the levels of neurotransmitters in the brain were determined. Preconditioning of CrCi-CDs significantly reduced ischemic lesion volume and blood–brain-barrier (BBB) permeability, improved neurologic deficits, decreased the level of TNF-α and IL-6 in MCAO rats, inhibited excitatory neurotransmitters aspartate (Asp) and glutamate (Glu), and increased the level of 5-hydroxytryptamine (5-HT). The RNA-Sequencing results reveal that further potential mechanisms behind the activities may be related to the anti-inflammation effects and inhibition of neuroexcitatory toxicity.ConclusionCrCi-CDs performs neuroprotective effect on cerebral ischemia and reperfusion injury, and the mechanisms may correlate with its anti-inflammatory action, which suggested that CrCi-CDs have potential value in clinical therapy on the acute apoplexy cases in combination with thrombolytic drugs.Graphic abstract

Current State of Stroke Care in the Philippines.

Stroke remains the leading cause of disability and death in the Philippines. Evaluating the current state of stroke care, the needed resources, and the gaps in health policies and programs is crucial to decrease stroke-related mortality and morbidity effectively. This paper aims to characterize the Philippines' stroke system of care and network using the World Health Organization health system building blocks framework. To integrate existing national laws and policies governing stroke and its risk factors dispersed across many general policies, the Philippine Department of Health (DOH) institutionalized a national policy framework for preventing and managing stroke. Despite policy reforms, government financing coverage remains limited. In terms of access to medicines, the government launched its stroke medicine access program (MAP) in 2016, providing more than 1,000 vials of recombinant tissue plasminogen activator (rTPA) or alteplase subsidized to selected government hospitals across the country. However, DOH discontinued the program due to the lack of neuroimaging machines and organized system of care to support the provision of the said medicine. Despite limited resources, stroke diagnostics and treatment facilities are more concentrated in urban settings, mostly in private hospitals, where out-of-pocket expenditures prevail. These barriers to access are also reflective of the current state of human resource on stroke where medical specialists (e.g., neurologists) serve in the few tertiary and training hospitals situated in urban settings. Meanwhile, there is no established unified national stroke registry thus, determining the local burden of stroke remains a challenge. The lack of centralization and fragmentation of the stroke cases reporting system leads to reliance on data from hospital records or community-based stroke surveys, which may inaccurately depict the country's actual stroke incidence and prevalence. Based on these gaps, specific recommendations geared toward systems approach - governance, financing, information system, human resources for health, and medicines were identified.

The dawn of precision medicine in stroke.

In the last decades, knowledge regarding stroke pathophysiology greatly increased. Information regarding mechanism and pathogenesis of brain ischemia derived from basic, translational and clinical studies allowed the design of randomized clinical trials (RCT) that by using advanced brain imaging methods evaluated the role of individual patterns of penumbra and perfusion in the extension of therapeutic windows for reperfusion treatments [1,2].

Frailty and cerebrovascular disease: Concepts and clinical implications for stroke medicine.

Frailty is a distinctive health state in which the ability of older people to cope with acute stressors is compromised by an increased vulnerability brought by age-associated declines in physiological reserve and function across multiple organ systems. Although closely associated with age, multimorbidity, and disability, frailty is a discrete syndrome that is associated with poorer outcomes across a range of medical conditions. However, its role in cerebrovascular disease and stroke has received limited attention. The estimated rise in the prevalence of frailty associated with changing demographics over the coming decades makes it an important issue for stroke practitioners, cerebrovascular research, clinical service provision, and stroke survivors alike. This review will consider the concept and models of frailty, how frailty is common in cerebrovascular disease, the impact of frailty on stroke risk factors, acute treatments, and rehabilitation, and considerations for future applications in both cerebrovascular clinical and research settings.

Deep Learning-Based Functional Independence Measure Score Prediction After Stroke in Kaifukuki (Convalescent) Rehabilitation Ward Annexed to Acute Care Hospital.

IntroductionPrediction models of functional independent measure (FIM) score after kaifukuki (convalescent) rehabilitation ward (KRW) are needed to decide the treatment strategies and save medical resources. Statistical models were reported, but their accuracies were not satisfactory. We made such prediction models using the deep learning (DL) framework, Prediction One (Sony Network Communications Inc., Tokyo, Japan).MethodsOf the 559 consecutive stroke patients, 122 patients were transferred to our KRW. We divided our 122 patients’ data randomly into halves of training and validation datasets. Prediction One made three prediction models from the training dataset using (1) variables at the acute care ward admission, (2) those at the KRW admission, and (3) those combined (1) and (2). The models’ determination coefficients (R2), correlation coefficients (rs), and residuals were calculated using the validation dataset.ResultsOf the 122 patients, the median age was 71, length of stay (LOS) in acute care ward 23 (17-30) days, LOS in KRW 53 days, total FIM scores at the admission of KRW 85, those at discharge 108. The mean FIM gain and FIM efficiency were 19 and 0.417. All patients were discharged home. Model (1), (2), and (3)’s R2 were 0.794, 0.970, and 0.972. Their mean residuals between the predicted and actual total FIM scores were -1.56±24.6, -4.49±17.1, and -2.69±15.7.ConclusionOur FIM gain and efficiency were better than national averages of FIM gain 17.1 and FIM efficiency 0.187. We made DL-based total FIM score prediction models, and their accuracies were superior to those of previous statistically calculated ones. The DL-based FIM score prediction models would save medical costs and perform efficient stroke and rehabilitation medicine.

Association between use of cardiovascular medicines and risk of mild cognitive function impairment and dementia amongst people living with cardiovascular diseases: a systematic review protocol.

The objective of this review is to investigate the association between the use of cardiovascular medicines and the risk of mild cognitive function impairment and dementia in people with cardiovascular disease. Cardiovascular disease is one of the most important modifiable factors for mild cognitive function impairment and dementia. The current evidence about the effectiveness of cardiovascular disease medicine on the risk of dementia is inconclusive; hence, it is imperative to conduct a comprehensive investigation on the effect of cardiovascular disease medicine on the risk of mild cognitive function impairment and dementia. This review will include studies involving participants (age ≥18 years) who were using cardiovascular medicine for hypertension, myocardial infarction, atrial fibrillation, stroke, or heart failure. The eligible studies will include observational studies and randomized controlled trials. MEDLINE (Ovid), Embase (Ovid), and PsycINFO (Ovid) will be searched from 2000 to the present. We will only include studies published in English. Titles, abstracts, and full texts will be screened by authors independently. The methodological quality of included studies will be assessed using the JBI critical appraisal checklist for observational studies and randomized controlled trials. The data to be extracted will include the basic study characteristics, populations, drug groups, clinical indicators, and outcomes. Studies will be pooled using statistical meta-analysis, where possible. Alternatively, the findings will be presented in narrative form where statistical pooling is not possible. PROSPERO CRD42020175386.