Vascular Cognitive Disorders Research Articles

The role of oxidative stress in the development of vascular cognitive disorders

Vascular cognitive impairment (VCI) is one of the most serious problems of clinical neurology, being the second most common cause of dementia. VCI covers a range of disorders in which vascular factors cause or contribute to cognitive decline. Among the main risk factors for VCI are old age and vascular factors, which lead to endothelial dysfunction and damage, which, in turn, can cause neurovascular dysfunction, increased permeability of the blood-brain barrier, and microvascular thrombosis. Oxidative stress is one of the most important mechanisms for the development of VCI that indicates the need for the use of agents with antioxidant activity. One of these drugs is ethylmethylhydroxypyridine succinate (mexidol). Mexidol is a drug with marked antioxidant and antihypoxic activities. The clinical efficacy of mexidol in relation to VCI has been demonstrated in many studies.

Meta-Analysis of Risk Factors of Vascular Cognitive Disorder in Acute Cerebral Infarction Patients

Objectives: To identify the main risk factors of vascular cognitive impairment in patients with acute cerebral infarction by Meta-analysis, and provide references for the effective prevention of the cognitive impairment in stroke patients. Methods: To retrieve the observational research literatures that refer to the risk factors of vascular cognitive impairment in patients with ischemic stroke, which are published on China National Knowledge Infrastructure (CNKI), Wanfang and Weipu Chinese databases. The screening and data extraction of these literatures are independently completed by two researchers, who also give the quality evaluation of the literatures according to the evaluation criterion of the Australian JBI Evidence-Based Health Care Center. Then, Meta-analysis is conducted by using Revman5.3 software. Results: There are twenty-eight articles selected from 1507 literatures, with a total of 10,711 cases and 50 risk factors included. Among them, there are combined effects of ten factors which have statistical significance, such as infarction area, alcohol consumption, smoking, hyper homocysteinemia, hypertension, diabetes mellitus, age, history of cerebral infarction, hyperlipoidemia and education level. The relational merging OR value and 95% CI between the type-variable factors and cognitive impairment are 3.25 (1.84, 5.76); 2.98 (2.58, 3.45); 2.79 (1.69, 4.59); 2.35 (1.93, 2.85); 2.25 (1.86, 2.71); 2.14 (2.10, 2.18); 1.82 (1.62, 2.03); 1.54 (1.24, 1.92); 1.45 (1.34, 1.56); 0.83 (0.78, 0.89). Conclusion: Infarction area, alcohol consumption, smoking, hyper homocysteinemia, hypertension, diabetesmellitus, age, history of cerebral infarction, hyperlipoidemia and low education level are the main risk factors for vascular cognitive impairment in patients with acute cerebral infarction. Clinical nursing staff should include it into the routine assessment of patients with acute cerebral infarction and actively prevent and intervene.

Meta-Analysis of Risk Factors of Vascular Cognitive Disorder in Acute Cerebral Infarction Patients

Meta-Analysis of Risk Factors of Vascular Cognitive Disorder in Acute Cerebral Infarction Patients

WITHDRAWN: Comorbid amyloid- ß pathology affects clinical and imaging features in VCD

IntroductionTo date, the clinical relevance of comorbid amyloid-β (Aβ) pathology in patients with vascular cognitive disorders (VCD) is largely unknown. MethodsWe included 218 VCD patients with available cerebrospinal fluid Aβ42 levels. Patients were divided into Aβ+ mild-VCD (n = 84), Aβ− mild-VCD (n = 68), Aβ+ major-VCD (n = 31), and Aβ− major-VCD (n = 35). We measured depression with the Geriatric Depression Scale, cognition with a neuropsychological test battery and derived white matter hyperintensities (WMH) and gray matter atrophy from MRI. ResultsAβ− patients showed more depressive symptoms than Aβ+. In major-VCD group, Aβ− patients performed worse on attention (P = .02) and executive functioning (P = .008) than Aβ+. We found no cognitive differences in patients with mild VCD. In mild-VCD group, Aβ− patients had more WMH than Aβ+ patients, whereas conversely, in major-VCD group, Aβ+ patients had more WMH. Atrophy patterns did not differ between Aβ+ and Aβ− VCD group. DiscussionComorbid Aβ pathology affects the manifestation of VCD, but effects differ by severity of VCD.

Clinical Relevance of Cerebral Small Vessel Diseases.

Clinical Relevance of Cerebral Small Vessel Diseases.

Longer Term Effects of Diet and Exercise on Neurocognition: 1-Year Follow-up of the ENLIGHTEN Trial.

To evaluate the longer term changes in executive functioning among participants with cardiovascular disease (CVD) risk factors and cognitive impairments with no dementia (CIND) randomized to a diet and exercise intervention. A 2 (Exercise) × 2 (Dietary Approaches to Stop Hypertension [DASH] eating plan) factorial randomized clinical trial. Academic tertiary care medical center. Volunteer sample of 160 older sedentary adults with CIND and at least one additional CVD risk factor enrolled in the ENLIGHTEN trial between December 2011 and March 2016. Six months of aerobic exercise (AE), DASH diet counseling, combined AE + DASH, or health education (HE) controls. Neurocognitive battery recommended by the Neuropsychological Working Group for Vascular Cognitive Disorders including measures of executive function, memory, and language/verbal fluency. Secondary outcomes included the Clinical Dementia Rating-Sum of Boxes (CDR-SB), Six-Minute Walk Distance (6MWD), and CVD risk including blood pressure, body weight, and CVD medication burden. Despite discontinuation of lifestyle changes, participants in the exercise groups retained better executive function 1 year post-intervention (P = .041) compared with non-exercise groups, with a similar, albeit weaker, pattern in the DASH groups (P = .054), without variation over time (P's > .867). Participants in the exercise groups also achieved greater sustained improvements in 6MWD compared with non-Exercise participants (P < .001). Participants in the DASH groups exhibited lower CVD risk relative to non-DASH participants (P = .032); no differences in CVD risk were observed for participants in the Exercise groups compared with non-Exercise groups (P = .711). In post hoc analyses, the AE + DASH group had better performance on executive functioning (P < .001) and CDR-SB (P = .011) compared with HE controls. For participants with CIND and CVD risk factors, exercise for 6 months promoted better executive functioning compared with non-exercisers through 1-year post-intervention, although its clinical significance is uncertain. J Am Geriatr Soc 68:559-568, 2020.

Large-scale network dysfunction in vascular cognitive disorder supports connectional diaschisis in advanced arteriosclerosis.

Background and purposeThe interrelation of cognitive performance, cerebrovascular damage and brain functional connectivity (FC) in advanced arteriosclerosis remains unclear. Our aim was to investigate the associations between FC, white matter damage and cognitive impairment in carotid artery disease.MethodsSeventy‐one participants with a recent cerebrovascular event and with written informed consent underwent resting‐state functional magnetic resonance imaging and the Addenbrooke's Cognitive Examination – Revised (ACE‐R). Network and inter‐hemispheric FC metrics were compared between cognitively normal and impaired subjects, and interrelated with cognition. In order to explore the nature of FC changes, their associations with microstructural damage of related white matter tracts and cognitive performance were investigated, followed by mediation analysis.ResultsParticipants with global cognitive impairment showed reduced FC compared to the cognitively intact subjects within the central executive network (CEN), and between hemispheres. Patients with executive dysfunction had decreased CEN FC whilst patients with memory loss demonstrated low FC in both the CEN and the default mode network (DMN). Global performance correlated with connectivity metrics of the CEN hub with DMN nodes, and between hemispheres. Cingulum mean diffusivity (MD) was negatively correlated with ACE‐R and CEN–DMN FC. The cingulum MD–cognition association was partially mediated by CEN–DMN FC.ConclusionsLong‐range functional disconnection of the CEN with DMN nodes is the main feature of cognitive impairment in elderly subjects with symptomatic carotid artery disease. Our findings provide further support for the connectional diaschisis concept of vascular cognitive disorder, and highlight a mediation role of functional disconnection to explain associations between microstructural white matter tract damage and cognitive impairment.

Nontraumatic Pediatric Intracerebral Hemorrhage.

Nontraumatic Pediatric Intracerebral Hemorrhage.

Idiopathic Normal-Pressure Hydrocephalus: Diagnostic Accuracy of Automated Sulcal Morphometry in Patients With Ventriculomegaly.

Idiopathic normal-pressure hydrocephalus (iNPH) is a treatable cause of gait and cognitive impairment. iNPH should be differentiated from ventriculomegaly secondary to brain atrophy to choose the best therapeutic option (ventriculoperitoneal shunt vs medical management). To determine the diagnostic accuracy of automated sulcal morphometry to differentiate patients with iNPH from patients with ventriculomegaly of neurodegenerative origin. Thirty-eight consecutive patients with iNPH (shunt responsive n=31, nonresponsive n=7), 35 with vascular cognitive disorder, and 25 age- and sex-matched healthy controls were prospectively included and underwent cognitive evaluation and 3T brain magnetic resonance imaging. Sulcal opening of 10 sulci of interest was retrospectively measured using an automated surface-based approach from the 3-dimensional T1-weighted images. Receiver-operating characteristic curve analyses determined the best parameter to identify iNPH patients. The best parameter to discriminate shunt-responsive iNPH from patients with vascular cognitive disorder and healthy controls was the ratio between calcarine sulcus and cingulate sulcus opening with an area under the curve of 0.94 (95% CI: 0.89, 0.99). A cut-off value of 0.95 provided the highest sensitivity (96.8%) and specificity (83.3%). This preliminary study showed that automated sulcal morphometry may help the neurosurgeon to identify iNPH patients and to exclude other causes of ventriculomegaly.

The Diagnostic Value Of Mattis Dementia Rating Scale- Initiation Perseveration Subscale In Vascular Cognitive Disorders

Vascular cognitive disorder (VCD)2 comprises a heterogeneous group of cerebrovascular disorders, leading to a continuum of cognitive impairment, ranging from the level of mild cognitive impairment or mild vascular cognitive disorder (VCDM) to full-blown vascular dementia or major vascular cognitive disorder (VCDD).

The role of arterial and venous blood flow and cerebrospinal fluid flow disturbances in the development of cognitive impairments in cerebral microangiopathy

Cerebral microangiopathy (CMA) is the main cause of vascular cognitive disorders, the leading cause of mixed dementia, and the main modifiable risk factor in Alzheimer’s disease. Study objective. To investigate the role of arterial and venous blood flow and cerebrospinal fluid flow, as well as their interrelation in the development of cognitive disorders in patients with CMA. Materials and methods. Ninety-six patients (32 men and 64 women, mean age 60.6±6.3 years) with cognitive complaints and CMA, diagnosed according to the STRIVE international MRI criteria, were examined. The severity of cognitive disturbance was assessed based on the overall cognitive level (MoCA scale and independence in daily life), the results of memory tests (10 words memory test) and executive brain function tests (TMT B-A). Phase contrast MRI was used to measure blood flow in the internal carotid and vertebral arteries (total arterial blood flow), the internal jugular veins and the straight and superior sagittal sinuses, as well as the aqueductal cerebrospinal fluid flow. Arterial pulsation and intracranial compliance indices were calculated. Results. Dementia and severe memory impairment were statistically significantly associated with an increase in the arterial pulsation index, intracranial compliance index and the aqueductal CSF stroke volume. Significant disturbances in brain executive function were also associated with a decrease in the total arterial blood flow, as well as the venous blood flow in the straight and superior sagittal sinuses. The characteristics of blood flow and cerebrospinal fluid are closely related, and the arterial pulsation index affects all the studied parameters. Conclusion. The severity of cognitive disturbance in CMA is determined by an increase in the arterial pulsation index, the intracranial compliance index and the aqueductal CSF stroke volume, while the severity of dysregulation disorders is determined by a concurrent decrease in the total arterial blood flow and venous blood flow in the straight and superior sagittal sinuses. The specific changes in blood flow and CSF flow and their interrelation in patients with cognitive impairment due to CMA suggest the pathogenetic importance of cerebral hydrodynamic disturbances in the aetiology of brain damage and the development of cognitive impairment in CMA.

The Vascular Behavioral and Cognitive Disorders criteria for vascular cognitive disorders: a validation study.

The Vascular Behavioral and Cognitive Disorders (VASCOG) criteria for vascular cognitive disorders were published in 2014, but their concurrent and predictive validity have not been examined. Participants (N=165, aged 49-86years) were from Sydney Stroke Study, a longitudinal study of post-stroke cognitive impairment and dementia. Diagnoses using the National Institute of Neurological Disorders and Stroke - Association Internationale pour la Recherché et l'Enseignement en Neurosciences (NINDS-AIREN), the Alzheimer's Disease Diagnostic and Treatment Centers (ADDTC) and the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), criteria for vascular dementia (VaD) were made by consensus at multidisciplinary case conferences. Diagnoses for mild vascular cognitive disorder (mVCD) and VaD using VASCOG, DSM-5 and the Vascular Impairment of Cognition Classification Consensus Study (VICCCS) criteria were made by two study authors. Agreement levels between criteria sets were examined using Cohen's kappa (κ). The ability of VaD diagnoses to predict mortality over 10years and of mVCD to predict dementia over 5years was investigated. The VASCOG criteria yielded rates of mVCD slightly lower than for DSM-5 and VICCCS. VaD rates were similar for all criteria, although slightly lower for DSM-IV. Agreement between the VASCOG, VICCCS and DSM-5 criteria was excellent for VaD and mVCD (κ=0.83-1.0), but lower for VaD between VASCOG and the other criteria (κ=0.47-0.63). VaD-based mortality predictions were similar for the VASCOG, VICCCS and DSM-5 criteria, and higher than those for other criteria. The prediction of incident dementia within 5years from mVCD was slightly lower with VASCOG criteria than with DSM-5 and VICCCS criteria. The VASCOG criteria have greater sensitivity, modest concurrent validity and better predictive validity than older criteria for VaD, but are comparable to DSM-5 and VICCCS criteria. Their operationalization and inclusion of a mild VCD category make them useful for clinical and research applications.

Vascular Cognitive Disorder.

The term vascular cognitive disorder (VCD) refers to a heterogeneous group of disorders in which the primary feature is cognitive impairment attributable to cerebrovascular disease (CVD). This includes not only vascular dementia (VaD) but also cognitive impairment of insufficient severity to meet diagnostic criteria for dementia. VCD is recognized as the second most common cause of dementia after Alzheimer's disease (AD), but prevalence rates vary widely according to the diagnostic criteria employed. There have been recent attempts to standardize diagnostic criteria. VCD incorporates a range of neuropathological mechanisms including poststroke impairment, small and large vessel disease, and cases of mixed-pathology, with CVD interacting with AD and other neuropathologies. Recent neuroimaging data have improved our understanding of the etiology of VCD. Symptomatic treatments for VaD have modest benefit and there is increased focus on the primary and secondary preventative benefits of vascular risk factor control.

A multicenter observation study of the efficacy of cortexin and recognan (citicoline) in the treatment of cognitive impairments in chronic cerebrovascular pathology

To make a critical assessment of the therapeutic effect of complex therapy with cortexin and recognan (citicoline) for cognitive impairments in patients with chronic cerebrovascular pathology. Presented is an analysis of results of the multicenter observation program to assess the efficacy of cortexin and recognan (citicoline) in the treatment of cognitive impairments in patients with chronic cerebrovascular pathology. Three hundred and nine patients with chronic cerebrovascular pathology, including 134 (43.4%) men and 175 (56.6%) women, aged from 30 to 80, average age 63.4±9.4 years, with confirmed cognitive deficit were examined. The diagnosis was established on the basis of complaints, case reports, the results of CT/MRI studies, as well as assessments of the neurological status and cognitive functions. Cognitive impairments were confirmed by the number of points on the Mini-mental state examination (MMSE) and the Clock drawing test. The assessment of depression was made with the Mini Geriatric Depression Scale (MGDS). All patients received cortexin and recognan (citicoline) ('Geropharm', Russia) at doses 10 mg/day for 10 days and 1000 mg/day for 1 month, respectively. Complex therapy with cortexin and recognan (citicoline) showed high efficacy in the treatment of vascular cognitive disorders. The results of the study allow us to recommend the complex administration of cortexin and recognan (citicoline) ('Geropharm', Russia) in doses of 10 mg/day for 10 days and 1000 mg/day for 1 month, respectively, for chronic cerebrovascular pathology.

The 2018 Stockport Vascular Neuro Cognitive Disorder Investigation, Treatment and Annual Review Guidelines (Including the Spectrum from Mild Vascular Cognitive Impairment to Vascular Dementia) Supporting Primary and Secondary Care Physicians

The 2018 Stockport Vascular Neuro Cognitive Disorder Investigation, Treatment and Annual Review Guidelines (Including the Spectrum from Mild Vascular Cognitive Impairment to Vascular Dementia) Supporting Primary and Secondary Care Physicians

EEG and Clinical Factors Associated with Mild Cognitive Impairment in Coronary Artery Disease Patients

Background: Although an impaired cognitive status in patients with coronary artery disease (CAD) is not rare, the neurophysiological and clinical indicators of mild cognitive impairment (MCI) have been insufficiently investigated so far. Methods: EEG and neuropsychological testing as well as clinical examination were performed on 122 patients with CAD, who were divided into two groups, those with MCI (n = 60; mean age 57.4 ± 5.81 years) and those without MCI (n = 62; mean age 57.0 ± 5.04 years). Binary logistic regression was used to identify the relationship between EEG and clinical variables and the probability of MCI. Results: Higher theta/alpha ratios, theta1 rhythm power with closed eyes in the frontal and occipital areas of the left hemisphere, and alpha2 rhythm power with eyes open in the frontal areas of the right hemisphere were associated with an increased risk for MCI in CAD patients. A low educational level, type 2 diabetes mellitus, and severe coronary lesions according to the SYNTAX Score (≥23 points) increased the risk for MCI as well. Conclusions: The findings of our study show that a theta activity increase in frontal and occipital sites, as well as high theta/alpha ratios, may be considered as the earliest EEG markers of vascular cognitive disorders.

Diagnosis and treatment of chronic cerebral ischemia. DIAMANT study results

The diagnosis of chronic cerebral ischemia (CHI) is based on the presence of vascular cognitive disorders (CD). Many patients diagnosed with CHI have other neurological or mental illnesses (primary headaches, vestibulopathies, anxiety and depressive disorders), which, unfortunately, are not diagnosed. Prevention of stroke, which is based on the correction of risk factors (smoking, alcohol abuse, low physical activity, and obesity), the treatment of hypertension, diabetes and other diseases is of major importance in the management of patients with CHI. Inhibitors of central acetyl cholinesterase and akatinol memantine showed efficacy in the management of significant vascular CD. The article discusses the issues of use of Divaza for the management of CHI, provides the results of DIAMANT multicentre observational study.

A Role for New Brain Magnetic Resonance Imaging Modalities in Daily Clinical Practice: Protocol of the Prediction of Cognitive Recovery After Stroke (PROCRAS) Study.

BackgroundCognitive impairment is common after acute ischemic stroke, affecting up to 75% of the patients. About half of the patients will show recovery, whereas the others will remain cognitively impaired or deteriorate. It is difficult to predict these different cognitive outcomes.ObjectiveThe objective of this study is to investigate whether diffusion tensor imaging–based measures of brain connectivity predict cognitive recovery after 1 year, in addition to patient characteristics and stroke severity. A specific premise of the Prediction of Cognitive Recovery After Stroke (PROCRAS) study is that it is conducted in a daily practice setting.MethodsThe PROCRAS study is a prospective, mono-center cohort study conducted in a large teaching hospital in the Netherlands. A total of 350 patients suffering from an ischemic stroke who screen positive for cognitive impairment on the Montreal Cognitive Assessment (MoCA<26) in the acute stage will undergo a 3Tesla-Magnetic Resonance Imaging (3T-MRI) with a diffusion-weighted sequence and a neuropsychological assessment. Patients will be classified as being unimpaired, as having a mild vascular cognitive disorder, or as having a major vascular cognitive disorder. One year after stroke, patients will undergo follow-up neuropsychological assessment. The primary endpoint is recovery of cognitive function 1 year after stroke in patients with a confirmed poststroke cognitive disorder. The secondary endpoint is deterioration of cognitive function in the first year after stroke.ResultsThe study is already ongoing for 1.5 years, and thus far, 252 patients have provided written informed consent. Final results are expected in June 2019.ConclusionsThe PROCRAS study will show the additional predictive value of diffusion tensor imaging-based measures of brain connectivity for cognitive outcome at 1 year in patients with a poststroke cognitive disorder in a daily clinical practice setting.Registered Report IdentifierRR1-10.2196/9431

Prevalence of Poststroke Neurocognitive Disorders Using National Institute of Neurological Disorders and Stroke-Canadian Stroke Network, VASCOG Criteria (Vascular Behavioral and Cognitive Disorders), and Optimized Criteria of Cognitive Deficit.

The prevalence of poststroke neurocognitive disorder (NCD) has yet to be accurately determined. The primary objective of the present study was to optimize operationalization of the criterion for NCD by using an external validity criterion. The GRECOG-VASC cohort (Groupe de Réflexion pour l'Évaluation Cognitive Vasculaire) of 404 stroke patients with cerebral infarct (91.3%) or hemorrhage (18.7%) was assessed 6 months poststroke and 1003 healthy controls, with the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network standardized battery. Three dimensions of the criterion for cognitive impairment were systematically examined by using the false-positive rate as an external validity criterion. Diagnosis of mild and major NCD was based on the VASCOG criteria (Vascular Behavioral and Cognitive Disorders). The mechanisms of functional decline were systematically assessed. The optimal criterion for cognitive impairment was the shortened summary score (ie, averaged performance for action speed, executive functions, and language) because it was associated with the highest (P=0.0001) corrected true-positive rate (43.5%) and a false-positive rate ≤5%. Using this criterion, the mean (95% confidence interval) prevalence of poststroke NCD was 49.5% (44.6-54.4), most of which corresponded to mild NCD (39.1%; 95% confidence interval, 34.4-43.9) rather than dementia (10.4%; 95% confidence interval, 7.4-13.4). This study is the first to have optimized the operationalization of the criterion for poststroke cognitive impairment. It documented the prevalence of poststroke NCD in the GRECOG-VASC cohort and showed that mild cognitive impairment accounts for 80% of the affected patients. Finally, the method developed in the present study offers a means of harmonizing the diagnosis of NCD. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01339195.

Preparation and Regeneration of Protoplasts from the Ethyl Vincamine Producing Fungus CH1 (Geomyces sp.)

Vinpocetine, a semi-synthetic compound derived from the alkaloid vincamine, exhibits effective pharmacological activities for the treatment and prevention of cerebrovascular circulation and vascular cognitive disorders. Vinpocetine can be produced through a one-step chemical reaction beginning with ethyl vincamine, and a two-step chemical reaction beginning with vincamine. In our previous study, the endophytic fungus CH1, Geomyces sp., was isolated and identified as a producer of ethyl vincamine, which was first obtained by endophytic fungal fermentation. However, the production was largely limited. Fungal protoplasts are a valuable experimental tool for physiological and genetic research such as protoplast fusion, gene transfer and metabolite production. In this paper, we optimized some key factors for the preparation and regeneration of protoplasts from strain CH1. Using an enzymes mixture consisting of cellulase (2.0%, w/v), glusulase (3.0%, w/v) and driselase (1.0%, w/v) in osmotic stabilizer (0.7 mol/L NaCl), the highest yield of protoplasts (6.78×107/mL) was obtained with mycelia after 72 h at pH 5.0-6.0 by digesting for 1.5 h at 30°C. After purification of the prepared protoplasts, they were regenerated in the regeneration medium using a bilayer plate culture method.