Stroke injury, cognitive impairment and vascular dementia

Post-stroke dementia (PSD) is a clinical entity that encompasses all types of dementia following an index stroke. Current evidence suggests that 25-30% of ischemic stroke survivors develop immediate or delayed vascular cognitive impairment or vascular dementia. The type of stroke can be either ischemic, hemorrhagic or hypoperfusive. There are multiple risk factors for PSD including older age, family history, genetic variants, low educational status, vascular comorbidities, prior transient ischemic attack or recurrent stroke and depressive illness. Pre-stroke dementia refers to the occurrence of cognitive impairment before the index stroke, which may be caused by a vascular burden as well as insidious neurodegenerative changes. Neuroimaging determinants of dementia after stroke include silent brain infarcts, white matter changes, lacunar infarcts and medial temporal lobe atrophy. Published clinical trials have not been promising and there is little information on whether PSD can be prevented using pharmacological agents. Control of vascular disease risk and prevention of recurrent strokes are key to reducing the burden of cognitive decline and post-stroke dementia. Modern imaging and analysis techniques will help to elucidate the mechanism of PSD and establish better treatment.

BACKGROUND AND PURPOSE A low risk of recurrent stroke and death after lacunar infarction has previously been reported, but follow-up has been limited to </=5 years. One hundred eighty patients with pure motor stroke, collected between 1983 and 1986 from a hospital-based stroke registry, were followed up until at least 10 years after the index stroke. Two patients were lost to follow-up. Survival status was determined from the official population registry and compared with survival rates of the Swedish population, matched for age and sex. Cox proportional hazards regression analyses were used to identify independent prognostic predictors. During follow-up 106 (60%) of the 178 patients died, most commonly as a result of coronary heart disease. During the first 5 years after the stroke, survival rates were similar to those of the general population. Beyond this time the risk of death was increased among patients with pure motor stroke, with an excess of 10 to 15 percent units compared with the general population. Independent determinants for death were age (P<0.01), male sex (P<0.01), and nonuse of acetylsalicylic acid (P=0.02). Recurrent stroke occurred in 42 (23.5%) of the patients, corresponding to an annual risk of 2.4%. Hypertension (P=0.025) and diabetes (P=0.024) were independent risk factors for recurrent stroke. For the first few years after lacunar infarct, the risk of death was similar to that of the general population, but later a clear excess of death was observed. The long-term prognosis in lacunar infarction appears less favorable than previously reported.

Stroke is the second leading cause of death after coronary heart disease in developed countries and is the greatest cause of disability and cognitive impairment. Risk factors for cognitive impairment and dementia after stroke are multifactorial including older age, family history, hypertension, arterial fibrillation, diabetes, genetic variants, low educational status, vascular comorbidities, prior transient ischaemic attack or recurrent stroke, depressive illness duration of a stroke, location, volume, intensity, and degree of neuronal degeneration, location and size of infarction after stroke, time interval after stroke other cerebral dysfunctions. The pathophysiology of stroke associated cognitive impairment is complex and recent molecular, cellular, and animal models studies have revealed that multiple cellular changes have been implicated, including altered redox state, mitochondrial dysfunction, disruption of the blood-brain barrier, perivascular spacing, glymphatic system impairment, microglia activation and amyloid-β deposition in the parenchyma of the brain. These studies have also evidenced the involvement of various transcription factors, intracellular adhesion molecules, and endogenous growth factors in the pathogenesis of cognitive impairment associated with stroke and providing scope for developing therapeutic strategies for treatment. This review summarizes the latest research findings on molecular mechanisms involved in cognitive impairment associated with stroke.

Neuropsychiatric Significance of Subcortical Hyperintensity

Post-stroke Dementia: Epidemiology, Mechanisms and Management

Background. Cognitive impairment in acute ischemic stroke has a negative impact on patients’ adaptability and quality life. They can result from acute ischemic brain damage affecting areas responsible for cognitive functions, or they can precede stroke. In the latter case, chronic cerebrovascular pathology and neurodegenerative process are the most common clinical variants. Their combination is considered within the concept of mixed cognitive impairment. In routine practice, magnetic resonance imaging (MRI) plays an important role, and visual semi-quantitative MR scales have been developed for the assessment of brain damage. Objective. To assess changes in white and gray matter in patients with lacunar and cardioembolic stroke using visual MR scales and to compare these data with the results of neuropsychological examination. Design and methods . We included 42 patients with cardioembolic and 52 patients with lacunar stroke and assessed changes in white and gray matter using 6 visual MR scales. A comprehensive neuropsychological examination was also performed. A correlation analysis was applied to assess the associations between the results of MR scales and impaired cognitive functions. Results. Patients with both lacunar and cardioembolic stroke subtypes, were characterized by a moderate degree of white matter damage. At the same time, patients with cardioembolic stroke tend to have more severe changes. In lacunar stroke, minor and moderate changes in gray predominate, while cardioembolic stroke is characterized by moderate and severe atrophy, which is reflected by the Koedam scales (0,000004) and atrophy of medial temporal lobe (0,000002). However, the results of the global cortical atrophy scale did not differ in these groups (0,902). Neuropsychological examination demonstrated that mild (44,2 % and 16,7 %, respectively) and moderate (46,2 % and 59,5 %, respectively) cognitive impairment predominates in both lacunar and cardioembolic stroke, and dementia is less common. Correlation analysis showed reliable links between structural brain damage and clinical features of cognitive impairment. Conclusion. Cardioembolic and lacunar strokes are characterized by moderate diffuse damage of white matter. The Wahlund and Scheltens scales are the most efficient for their detection. The greatest of degree gray matter damage was recorded in frontal lobes, in mediobasal regions of temporal lobes and parietal lobes in cardioembolic stroke and infratentorially and in basal ganglia in lacunar stroke. Both stroke subtypes are characterized by mild and moderate cognitive disorders, and dementia is registered only in isolated cases. The development of cognitive impairment correlates with topography and degree of white and gray matter damage.

Clinico-radiological predictors of vascular cognitive impairment (VCI) in patients with stroke: A prospective observational study

Frequency and Risk Factors of Vascular Cognitive Impairment Three Months after Ischemic Stroke in China: The Chongqing Stroke Study

Hypertension is a risk factor for cognitive impairment and dementia. Arterial stiffness could be involved in the mechanisms of vascular cognitive impairment and in Alzheimer's disease. We examined the association between arterial stiffness, assessed by carotid-femoral pulse wave velocity (PWV), and medial temporal lobe (MTL) atrophy, a biomarker of Alzheimer's disease. Elderly community-dwelling study participants (n = 149) with memory complaints were diagnosed with Alzheimer's disease (n = 62) or mild cognitive impairment (n = 87) at a memory clinic. PWV, peripheral and central blood pressure (SBP), and pulse pressure (PP) were measured. MTL was graded on MRI according to the Scheltens' scale. Mean age was 79.5 (SD = 5) years old, 36% of study participants were men. MTL was absent or discrete in 23.5%, moderate in 53.0% and severe in 23.5% of study participants. PWV was 9.3 (2.2) m/s in none or discrete, 11.1 (2.8) in moderate and 13.5 (4.0) in severe MTL atrophy (P < 0.0001). PWV, central SBP, and central PP were overall associated with MTL atrophy after adjustment for age, sex, antihypertensive treatments and white matter lesions, and further adjusted for mean BP for PWV, whereas peripheral SBP and PP were not associated with MTL atrophy. PWV was significantly associated with severe MTL atrophy [odds ratio = 3.69 (95% confidence interval = 1.69-8.05), P = 0.001] and marginally associated with moderate MTL atrophy [1.80 (0.92-3.53), P = 0.09]. Furthermore PWV was significantly associated with severe MTL atrophy in Alzheimer's disease and mild cognitive impairment study participants separately. The result of this study suggests a role of arterial stiffness in the pathogenesis of Alzheimer's disease.

The general objective of this thesis was to investigate the clinical features and prognosis of patients with vascular cognitive impairment (VCI) in a memory clinic setting. To this end, the TRACE-VCI study was initiated, resulting in a large, unique cohort of 860 patients from three Dutch outpatient clinics at two university hospitals. The first part of this thesis focused on the clinical features and cognitive profile of the patients included in the TRACE-VCI cohort. Chapter 2 described the design and clinical features of the TRACE-VCI cohort regarding type of vascular brain injury, severity of cognitive impairment and combination with other neurodegenerative etiologies. In this memory clinic population with VCI, the main types of vascular brain injury were moderate/severe WMH (46%), microbleed(s) (43%) and lacunar infarct(s) (11%). In total, 52% of patients showed dementia, in which 86% had a neurodegenerative etiology, mostly Alzheimer’s disease (79%). Chapter 3 showed that type and severity of vascular brain injury explained little of the variation in cognitive profile. The cognitive profile was remarkably similar across all types of vascular brain injury. Chapter 4 showed no different cognitive profile among sexes. Type of vascular brain injury did show differences between sexes; female patients showed larger WMH volumes, while males showed more non-lacunar and lacunar infarct(s). The most important difference was made by the presence of a positive CSF biomarker Alzheimer profile. A positive CSF biomarker Alzheimer profile by itself markedly affected cognitive performance on all domains showing worse performance on all cognitive domains, especially memory. This finding provides support for the theory that vascular brain injury lowers the threshold for symptoms of cognitive impairment in co-occurring Alzheimer pathology. Chapter 5 demonstrated that memory clinic patients with VCI and different types of vascular brain injury on MRI showed little differences in cognitive trajectories depending on type of vascular brain injury. Across the TRACE-VCI study population performance declined over time on all tests. The data provided some suggestion that lacunar and non-lacunar infarct(s) were associated with minor differences in tests evaluating attention and executive functioning. These subtle associations were mainly attributable to patients with dementia. Chapter 6 described the creation and external validation of a risk score to predict poor clinical outcome. In 688 patients, follow-up collection was performed after a mean of 2.1 years, in which 170 patients showed poor clinical outcome. We defined a composite primary outcome measure that was robust and clinically relevant including (1) substantial cognitive decline, (2) occurrence of a major cardiovascular event (MACE), (3) death and/or (4) institutionalization due to other reasons than cognitive decline. Age, clinical syndrome diagnosis, Disability Assessment for Dementia, Neuropsychiatric Inventory, medial temporal lobe atrophy most strongly predicted poor outcome and constituted the risk score. None of the vascular risk factors or types of vascular brain injury were predictive for poor clinical outcome. Validation of the prediction score in an independent cohort showed comparable predictive ability. Chapter 4 described no statistically significant differences in poor clinical outcome between sexes. In conclusion, the overall aim of the TRACE-VCI study was to investigate the clinical features and prognosis of patients with possible VCI in a memory clinic setting. This thesis showed that type of vascular brain injury in a memory clinic population explained little of the variance in cognitive profile and trajectory. The presence of co-existing Alzheimer pathology by itself markedly affected cognitive performance on all domains. Prediction of poor clinical outcome in the TRACE-VCI study was mainly influenced by age, type of cognitive impairment, MTA score, neuropsychiatric symptoms and disability in daily living on baseline visit. Also here, no vascular predictors were retained in this model.

Introduction: Cognitive impairment due to cerebro vascular disease is termed” vascular cognitive Impairment “(VCI) and forms a spectrum that includes vascular dementia and milder forms of cognitive impairment. Vascular cognitive impairment has some varied and diverse aetiology. This is particularly important as apart from age vascular risk factors, are the most important and presently the only treatable precursor to dementia. This prospective observational study was carried out in indept. Of medicine, GMC Bhopal. Methods: A standard protocol was applied at admission and 3 months after stroke, this protocol included clinical, functional and cognitive assessments, various lab tests and MMSE. Results: Amongst the various risk factors hypertension, diabetes mellitus, prior stroke, dyslipidemia, ischemic heart disease, tobacco chewing, smoking, family history of dementia was more frequently seen in vascular cognitive impairment group. In this study, the frequency of patients having post stroke vascular cognitive impairment (VCI)is 54%. 18%of the patients had VaD (Vascular dementia), 36% of the patients had VMCI(vascular mild cognitive impairment), 46% of the patients had NO VCI (no vascular cognitive impairment. There was significant association of risk factors like Hypertension (p=0.022) diabetes mellitus (P=0.038), dyslipidaemia (p=0.034), prior stroke(p=0.046) with development of vascular cognitive impairment. Post stroke dementia has considerable morbidity. Conclusion: The predictors of development of Vascular cognitive impairment following stroke in this study are lower educational status, Hypertension, Diabetes mellitus, Dyslipidemia, Prior stroke, urinary incontinence, High sys. BP, NIHSS score, LDL level, abnormal ECG, Strategic site lesion and greater severity of age related white matter changes.

A dvances in our understanding of vascular cognitive impairment (VCI) have springboarded from further elucidation of the role of vascular risk factors, surgical procedures, medications, and neuroimaging studies that are related to this condition. The main focus of this VCI review will highlight the relation of diabetes mellitus and hippocampal dysfunction in VCI; coronary artery bypass surgery and cognitive decline; the role of cerebral amyloid angiopathy (CAA) in vascular dysfunction; and a discussion of other cardiovascular risk factors, treatment, and neuroimaging findings related to disease progression; and histopathologic and genetic correlates.

Background/AimsTo explore the imaging changes and related risk factors of heart failure (HF) patients with cognitive impairment (CI).MethodsA literature search was systematically carried out in PubMed, Web of Science, Embase, and Cochrane Library. In this systematic review, important relevant information was extracted according to the inclusion and exclusion criteria. The methodological quality was assessed by three scales according to the different study types.ResultsFinally, 66 studies were included, involving 33,579 patients. In the imaging changes, the severity of medial temporal lobe atrophy (MTA) and the decrease of gray Matter (GM) volume were closely related to the cognitive decline. The reduction of cerebral blood flow (CBF) may be correlated with CI. However, the change of white matter (WM) volume was possibly independent of CI in HF patients. Specific risk factors were analyzed, and the data indicated that the increased levels of B-type natriuretic peptide (BNP)/N-terminal pro-B-type natriuretic peptide (NT-proBNP), and the comorbidities of HF, including atrial fibrillation (AF), diabetes mellitus (DM) and anemia were definitely correlated with CI in patients with HF, respectively. Certain studies had also obtained independent correlation results. Body mass index (BMI), depression and sleep disorder exhibited a tendency to be associated with CI. Low ejection fraction (EF) value (<30%) was inclined to be associated with the decline in cognitive function. However, no significant differences were noted between heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) in cognitive scores.ConclusionBNP/NT-proBNP and the comorbidities of HF including AF, DM and anemia were inextricably correlated with CI in patients with HF, respectively. These parameters were independent factors. The severity of MTA, GM volume, BMI index, depression, sleep disorder, and low EF value (<30%) have a disposition to associated with CI. The reduction in the CBF volume may be related to CI, whereas the WM volume may not be associated with CI in HF patients. The present systematic review provides an important basis for the prevention and treatment of CI following HF.

Objective To investigate the correlation between Framingham stroke risk profile(FSRP) and vascular cognitive impairment in stroke-free patients with cerebrovascular risk factors. Methods One hundred and eighty-four stroke-free subjects, selected from Zhejiang hospital, were divided into low risk group (56 subjects), moderate risk group (70 subjects) and high risk group (58 subjects) according to their FSRP score, and their cognitive function including memory ability, attention, executive function and language ability were assessed by Montreal cognitive assessment (MoCA), auditory verbal learning test(AVLT), digit symbol test, trail making test(TMT), digit span and verbal fluency test. Results The total MoCA scores which were (7.2±4.6), (13.8±3.9), (29.6±12.7)respectively, AVLT-delay recall scores which were(8.2±1.6), (6.7±1.4), (5.9±1.5)respectively, and digit symbol test score which were(34.7±9.3), (32.6±16.4), (29.7±13.6) respectively in low, intermediate and high risk groups, decreased with the increasing risk of stroke(P<0.05). The elapsed time in TMT-B which were (115.2±36.9)s, (147.6±44.8)s, (173.9±58.5)s respectively in low, intermediate and high risk groups, prolonged with the increasing risk of stroke (P<0.05). FSRP was associated with cognitive function, but inversely related to MoCA, AVLT-delay recall, digit symbol test, TMT-B and digit span fall back (P<0.05), but positively related to consuming time in TMT-B(P<0.05). Multivariate regression analysis showed that advanced age, hypertension, diabetes and smoking were the risk factors for vascular cognitive impairment(P<0.05). Conclusion Advanced age, smoking, hypertension and diabetes are the most important in vascular risk factors for cognitive impairment. Vascular risk factors can damage cognitive function with the increased risk of stroke, among which delayed recall and executive function are the main affected cognitive area. Key words: Vascular cognitive impairment; Framingham stroke risk profile; Risk factor

Besides cerebrovascular disease, medial temporal lobe atrophy (MTA), a neuroimaging finding suggestive of degenerative pathology, has been shown in vascular dementia (VaD). However, it is unknown to what extent MTA contributes to the pattern of cognitive impairment observed in VaD. Therefore, our purpose was to investigate the relative contribution of cerebrovascular disease and MTA to cognitive impairment in patients fulfilling diagnostic criteria for VaD. We examined 590 patients (374 men; mean age, 73 years; standard deviation, 8) with probable VaD according to the National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences criteria at inclusion into a multicenter clinical trial. Cerebrovascular disease and the degree of MTA were evaluated by using MRI. Cognitive testing included the Mini-Mental State Examination, and the vascular dementia assessment scale. On the basis of the operational definitions for the neuroimaging part of the National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences criteria, 485 (82.2%) patients had small vessel VaD and 153 (25.9%) had large vessel VaD. More than half (59.8%) of the patients had considerable MTA. Multiple linear regression analyses revealed that after correction for sex, age, education, and duration of dementia, neuropsychological tests showed that patients with higher grades of MTA or large vessel VaD had significantly worse general cognitive and executive functioning, whereas associations with small vessel disease were restricted to worse executive functioning. Both MTA and large vessel disease contribute to global cognitive impairment in VaD. Small vessel disease contributes to executive dysfunction.