Structural brain network measures are superior to vascular burden scores in predicting early cognitive impairment in post stroke patients with small vessel disease.
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ABSTRACT:
SUBMITTER: Du J
PROVIDER: S-EPMC6378318 | biostudies-literature | 2019
REPOSITORIES: biostudies-literature
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Structural brain network measures are superior to vascular burden scores in predicting early cognitive impairment in post stroke patients with small vessel disease.
Du Jing J Wang Yao Y Zhi Nan N Geng Jieli J Cao Wenwei W Yu Ling L Mi Jianhua J Zhou Yan Y Xu Qun Q Wen Wei W Sachdev Perminder P
NeuroImage. Clinical 20190205
<h4>Objectives</h4>In this cross-sectional study, we aimed to explore the mechanisms of early cognitive impairment in a post stroke non-dementia cerebral small vessel disease (SVD) cohort by comparing the SVD score with the structural brain network measures.<h4>Method</h4>127 SVD patients were recruited consecutively from a stroke clinic, comprising 76 individuals with mild cognitive impairment (MCI) and 51 with no cognitive impairment (NCI). Detailed neuropsychological assessments and multimoda ...[more]
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Project description:ObjectivesIn this cross-sectional study, we tested the construct validity of a "total SVD score," which combines individual MRI features of small-vessel disease (SVD) in one measure, by testing associations with vascular risk factors and stroke subtype.MethodsWe analyzed data from patients with lacunar or nondisabling cortical stroke from 2 prospective stroke studies. Brain MRI was rated for the presence of lacunes, white matter hyperintensities, cerebral microbleeds, and perivascular spaces independently. The presence of each SVD feature was summed in an ordinal "SVD score" (range 0-4). We tested associations with vascular risk factors, stroke subtype, and cerebral atrophy using ordinal regression analysis.ResultsIn 461 patients, multivariable analysis found that age (odds ratio [OR] 1.10, 95% confidence interval [CI] 1.08-1.12), male sex (OR 1.58, 95% CI 1.10-2.29), hypertension (OR 1.50, 95% CI 1.02-2.20), smoking (OR 2.81, 95% CI 1.59-3.63), and lacunar stroke subtype (OR 2.45, 95% CI 1.70-3.54) were significantly and independently associated with the total SVD score. The score was not associated with cerebral atrophy.ConclusionsThe total SVD score may provide a more complete estimate of the full impact of SVD on the brain, in a simple and pragmatic way. It could have potential for patient or risk stratification or early efficacy assessment in clinical trials of interventions to prevent SVD progression and may (after further testing) have a useful role in clinical practice.
| S-EPMC4180484 | biostudies-literature
Project description:ImportanceSecondary prevention interventions to reduce post-stroke cognitive impairment (PSCI) can be aided by the early identification of high-risk individuals who would benefit from risk factor modification.ObjectiveTo develop and evaluate a predictive model to identify patients at increased risk of PSCI over 5 years using data easily accessible from electronic health records.DesignCohort study with patients enrolled between 2003-2016 with follow-up through 2022.SettingPrimary care practices affiliated with two academic medical centers.ParticipantsIndividuals 45 years or older, without prior stroke or prevalent cognitive impairment, with primary care visits and an incident ischemic stroke between 2003-2016 (development/internal validation cohort) or 2010-2022 (external validation cohort).ExposuresPredictors of PSCI were ascertained from the electronic health record.Main outcomeThe outcome was incident dementia/cognitive impairment within 5 years and beginning 3 months following stroke, ascertained using ICD-9/10 codes. For model variable selection, we considered potential predictors of PSCI and constructed 400 bootstrap samples with two-thirds of the model derivation sample. We ran 10-fold cross-validated Cox proportional hazards models using a least absolute shrinkage and selection operator (LASSO) penalty. Variables selected in >25% of samples were included.ResultsThe analysis included 332 incident diagnoses of PSCI in the development cohort (n=3,741), and 161 and 128 incident diagnoses in the internal (n=1,925) and external (n=2,237) validation cohorts. The c-statistic for predicting PSCI was 0.731 (95% CI: 0.694-0.768) in the internal validation cohort, and 0.724 (95% CI: 0.681-0.766) in the external validation cohort. A risk score based on the beta coefficients of predictors from the development cohort stratified patients into low (0-7 points), intermediate (8-11 points), and high (12-35 points) risk groups. The hazard ratios for incident PSCI were significantly different by risk categories in internal (High, HR: 6.2, 95% CI 4.1-9.3; Intermediate, HR 2.7, 95% CI: 1.8-4.1) and external (High, HR: 6.1, 95% CI: 3.9-9.6; Intermediate, HR 2.8, 95% CI: 1.9-4.3) validation cohorts.Conclusions and relevanceFive-year risk of PSCI can be accurately predicted using routinely collected data. Model output can be used to risk stratify and identify individuals at increased risk for PSCI for preventive efforts.
| S-EPMC10863024 | biostudies-literature
Project description:BackgroundIdentifying whether acute stroke patients are at risk of cognitive decline could improve prognostic discussions and management. Structural computed tomography neuroimaging is routine in acute stroke, and may identify those at risk of post-stroke dementia or post-stroke cognitive impairment (PSCI).AimTo systematically review the literature to identify which stroke or pre-stroke features on brain computed tomography scans, performed at the time of stroke, are associated with post-stroke dementia or PSCI.Summary of reviewWe searched electronic databases to December 2020. We included studies reporting acute stroke brain computed tomography, and later diagnosis of a cognitive syndrome. We created summary estimates of size of unadjusted association between computed tomography features and cognition. Of 9536 citations, 28 studies (41 papers) were eligible (N = 7078, mean age 59.8-78.6 years). Cognitive outcomes were post-stroke dementia (10 studies), PSCI (17 studies), and one study analyzed both. Fifteen studies (N = 2952) reported data suitable for meta-analyses. White matter lesions (WML) (six studies, N = 1054, OR = 2.46, 95% CI = 1.25-4.84), cerebral atrophy (four studies, N = 558, OR = 2.80, 95% CI = 1.21-6.51), and pre-existing stroke lesions (three studies, N = 352, OR = 2.38, 95% CI = 1.06-5.32) were associated with post-stroke dementia. WML (four studies, N = 473, OR = 3.46, 95% CI = 2.17-5.52) were associated with PSCI. Other computed tomography features were either not associated with cognitive outcome, or there were insufficient data.ConclusionsCognitive impairment following stroke is of great concern to patients and carers. Features seen on visual assessment of acute stroke computed tomography brain scans are strongly associated with cognitive outcomes. Clinicians should consider when and how this information should be discussed with stroke survivors.
| S-EPMC9260488 | biostudies-literature
Project description:Cognitive impairment is a common complication observed after a stroke. Currently there are no definitively proven pharmacologic therapies for recovery from post-stroke cognitive impairment and vascular dementia. In this meta-analysis, we evaluated the efficacy and safety of cholinesterase inhibitors in their improvement of cognition in patients with post-stroke cognitive impairment and vascular dementia. We conducted a meta-analysis using seven eligible studies from 305 published articles. We investigated the differences in Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) scores, before and after cholinergic augmentation in patients with post-stroke cognitive impairment and vascular dementia. MMSE and ADAS-cog scores were also compared during the subsequent follow-up periods. MMSE score of patients with post-stroke cognitive impairment was increased after cholinergic augmentation throughout the 24 weeks with mean differences [MD] of 3.000, 1.732, 1.578 1.516, and 1.222, at 4, 4-8, 8-12, 12-18, and 18-24 weeks, respectively. In addition, ADAS-cog scores decreased at 6, 12, 18, and 24 weeks by pharmaceutical augmentation, but not with placebo with mean differences [MD] of -2.333, -2.913, -2.767, -2.416, and -1.859, respectively. This meta-analysis shows that acetylcholinesterase inhibitors maintain a stable pattern of improved cognitive function in patients with post stroke cognitive impairment and vascular dementia without the increased risk of side effects.
| S-EPMC7006920 | biostudies-literature
Project description:Introduction: Post-stroke cognitive impairment (PSCI) is common, but evidence on the impact of vascular risk factors is lacking. We explored the association between pre-stroke vascular risk factors and PSCI and studied the course of PSCI. Materials and Methods: Vascular risk factors were collected at baseline in stroke survivors (n = 635). Cognitive assessments of attention, executive function, memory, language, and the Montreal Cognitive Assessment (MoCA) were performed at 3 and/or 18 months post-stroke. Stroke severity was assessed with the National Institutes of Health Stroke Scale (NIHSS). PSCI was measured with global z; MoCA z-score; and z-score of the four assessed cognitive domains. Mixed-effect linear regression was applied with global z, MoCA z-score, and z-scores of the cognitive domains as dependent variables. Independent variables were the vascular risk factors (hypertension, hypercholesterolemia, smoking, diabetes mellitus, atrial fibrillation, coronary heart disease, previous stroke), time, and the interaction between these. The analyses were adjusted for age, education, and sex. There were between 5 and 25% missing data for the variables for PSCI. Results: Mean age was 71.6 years (SD 11.7); 42% were females; and the mean NIHSS score at admittance was 3.8 (SD 4.8). Regardless of vascular risk factors, global z, MoCA, and all the assessed cognitive domains were impaired at 3 and 18 months, with MoCA being the most severely impaired. Atrial fibrillation (AF) was associated with poorer language at 18 months and coronary heart disease (CHD) with poorer MoCA at 18 months (LR = 12.80, p = 0.002, and LR = 8.32, p = 0.004, respectively). Previous stroke was associated with poorer global z and attention at 3 and 18 months (LR = 15.46, p < 0.001, and LR = 16.20, p < 0.001). In patients without AF, attention improved from 3 to 18 months, and in patients without CHD, executive function improved from 3 to 18 months (LR = 10.42, p < 0.001, and LR = 9.33, p = 0.009, respectively). Discussion: Our findings indicate that a focal stroke lesion might be related to pathophysiological processes leading to global cognitive impairment. The poorer prognosis of PSCI in patients with vascular risk factors emphasizes the need for further research on complex vascular risk factor interventions to prevent PSCI.
| S-EPMC8374055 | biostudies-literature
Project description:The global burden of ischaemic strokes is almost 4-fold greater than haemorrhagic strokes. Current evidence suggests that 25-30% of ischaemic stroke survivors develop immediate or delayed vascular cognitive impairment (VCI) or vascular dementia (VaD). Dementia after stroke injury may encompass all types of cognitive disorders. States of cognitive dysfunction before the index stroke are described under the umbrella of pre-stroke dementia, which may entail vascular changes as well as insidious neurodegenerative processes. Risk factors for cognitive impairment and dementia after stroke are multifactorial including older age, family history, genetic variants, low educational status, vascular comorbidities, prior transient ischaemic attack or recurrent stroke and depressive illness. Neuroimaging determinants of dementia after stroke comprise silent brain infarcts, white matter changes, lacunar infarcts and medial temporal lobe atrophy. Until recently, the neuropathology of dementia after stroke was poorly defined. Most of post-stroke dementia is consistent with VaD involving multiple substrates. Microinfarction, microvascular changes related to blood-brain barrier damage, focal neuronal atrophy and low burden of co-existing neurodegenerative pathology appear key substrates of dementia after stroke injury. The elucidation of mechanisms of dementia after stroke injury will enable establishment of effective strategy for symptomatic relief and prevention. Controlling vascular disease risk factors is essential to reduce the burden of cognitive dysfunction after stroke. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock.
| S-EPMC4827373 | biostudies-literature
Project description:Subcortical small-vessel disease (SSVD) is a disorder well characterized from the clinical, imaging, and neuropathological viewpoints. SSVD is considered the most prevalent ischemic brain disorder, increasing in frequency with age. Vascular risk factors include hypertension, diabetes, hyperlipidemia, elevated homocysteine, and obstructive sleep apnea. Ischemic white matter lesions are the hallmark of SSVD; other pathological lesions include arteriolosclerosis, dilatation of perivascular spaces, venous collagenosis, cerebral amyloid angiopathy, microbleeds, microinfarcts, lacunes, and large infarcts. The pathogenesis of SSVD is incompletely understood but includes endothelial changes and blood-brain barrier alterations involving metalloproteinases, vascular endothelial growth factors, angiotensin II, mindin/spondin, and the mammalian target of rapamycin pathway. Metabolic and genetic conditions may also play a role but hitherto there are few conclusive studies. Clinical diagnosis of SSVD includes early executive dysfunction manifested by impaired capacity to use complex information, to formulate strategies, and to exercise self-control. In comparison with Alzheimer's disease (AD), patients with SSVD show less pronounced episodic memory deficits. Brain imaging has advanced substantially the diagnostic tools for SSVD. With the exception of cortical microinfarcts, all other lesions are well visualized with MRI. Diagnostic biomarkers that separate AD from SSVD include reduction of cerebrospinal fluid amyloid-? (A?)42 and of the ratio A?42/A?40 often with increased total tau levels. However, better markers of small-vessel function of intracerebral blood vessels are needed. The treatment of SSVD remains unsatisfactory other than control of vascular risk factors. There is an urgent need of finding targets to slow down and potentially halt the progression of this prevalent, but often unrecognized, disorder.
| S-EPMC5870030 | biostudies-literature
Project description:ObjectivePost-stroke cognitive impairment (PSCI) is resistant to treatment. Recent studies have widely applied repetitive transcranial magnetic stimulation (rTMS) to treat various brain dysfunctions, such as post-stroke syndromes. Nonetheless, a protocol for PSCI has not been established. Therefore, this study is aimed to evaluate the therapeutic effect of our high-frequency rTMS protocol for PSCI during the chronic phase of stroke.MethodsIn this prospective study, ten patients with PSCI were enrolled and received high-frequency rTMS on the ipsilesional dorsolateral prefrontal cortex (DLPFC) for 10 sessions (5 days per week for 2 weeks). Cognitive and affective abilities were assessed at baseline and 2 and 14 weeks after rTMS initiation. To investigate the therapeutic mechanism of rTMS, the mRNA levels of pro-inflammatory cytokines (interleukin (IL)-6, IL-1β, transforming growth factor beta [TGF-β], and tumor necrosis factor alpha [TNF-α]) in peripheral blood samples were quantified using reverse transcription polymerase chain reaction, and cognitive functional magnetic resonance imaging (fMRI) was conducted at baseline and 14 weeks in two randomly selected patients after rTMS treatment.ResultsThe scores of several cognitive evaluations, i.e., the Intelligence Quotient (IQ) of Wechsler Adult Intelligence Scale, auditory verbal learning test (AVLT), and complex figure copy test (CFT), were increased after completion of the rTMS session. After 3 months, these improvements were sustained, and scores on the Mini-Mental Status Examination and Montreal Cognitive Assessment (MoCA) were also increased (p < 0.05). While the Geriatric Depression Scale (GeDS) did not show change among all patients, those with moderate-to-severe depression showed amelioration of the score, with marginal significance. Expression of pro-inflammatory cytokines was decreased immediately after the ten treatment sessions, among which, IL-1β remained at a lower level after 3 months. Furthermore, strong correlations between the decrease in IL-6 and increments in AVLT (r = 0.928) and CFT (r = 0.886) were found immediately after the rTMS treatment (p < 0.05). Follow-up fMRI revealed significant activation in several brain regions, such as the medial frontal lobe, hippocampus, and angular area.ConclusionsHigh-frequency rTMS on the ipsilesional DLPFC may exert immediate efficacy on cognition with the anti-inflammatory response and changes in brain network in PSCI, lasting at least 3 months.
| S-EPMC8980431 | biostudies-literature
Project description:Despite promising preclinical data, few novel stroke therapies have shown efficacy in man. Efforts to improve standards in conduct and reporting of preclinical research are ongoing. In clinical trials, inconsistency in outcome measures led to regulatory agencies and funders mandating use of a core set of functional outcomes. Our aim was to describe functional outcome measures in preclinical stroke and vascular cognitive impairment (VCI) studies. From 14 high impact journals (January 2005-December 2015 inclusive), 91,956 papers were screened with 1302 full texts analyzed for stroke (ischemic and hemorrhagic) and 56 for VCI studies. In total, 636 (49%) stroke and 37 (66%) VCI papers reported functional outcome measures. There were 74 different functional assessments reported in stroke and 20 in VCI studies. Neurological deficit scores (74%) and Morris water maze (60%) were most commonly used in stroke and VCI, respectively. However, inconsistencies in methods used to assess and score recovery were noted. Neurological and behavioural functional outcome measures are increasingly used in preclinical stroke or VCI studies; however, there is substantial variation in methods. A strict standardized outcome set may not be suitable for translational work, but greater consistency in choice, application and reporting of outcomes may improve the science.
| S-EPMC6259321 | biostudies-literature
Project description:With increased numbers of older people a higher burden of neurological disorders worldwide is predicted. Stroke and other cerebrovascular diseases do not necessarily present with different phenotypes in Africa but their incidence is rising in tandem with the demographic change in the population. Age remains the strongest irreversible risk factor for stroke and cognitive impairment. Modifiable factors relating to vascular disease risk, diet, lifestyle, physical activity and psychosocial status play a key role in shaping the current spate of stroke related diseases in Africa. Hypertension is the strongest modifiable risk factor for stroke but is also likely associated with co-inheritance of genetic traits among Africans. Somewhat different from high-income countries, strokes attributed to cerebral small vessel disease (SVD) are higher >30% among sub-Saharan Africans. Raised blood pressure may explain most of the incidence of SVD-related strokes but there are likely other contributing factors including dyslipidaemia and diabetes in some sectors of Africa. However, atherosclerotic and cardioembolic diseases combined also appear to be common subtypes as causes of strokes. Significant proportions of cerebrovascular diseases are ascribed to various forms of infectious disease including complications of human immunodeficiency virus. Cerebral SVD leads to several clinical manifestations including gait disturbance, autonomic dysfunction and depression. Pathological processes are characterized by arteriolosclerosis, lacunar infarcts, perivascular spaces, microinfarcts and diffuse white matter changes, which can now all be detected on neuroimaging. Except for isolated cases of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy or CADASIL, hereditary arteriopathies have so far not been reported in Africa. Prevalence estimates of vascular dementia (2-3%), delayed dementia after stroke (10-20%) and vascular cognitive impairment (30-40%) do not appear to be vastly different from those in other parts of the world. However, given the current demographic transition in both urban and rural settings these figures will likely rise. Wider application of neuroimaging modalities and implementation of stroke care in Africa will enable better estimates of SVD and other subtypes of stroke. Stroke survivors with SVD type pathology are likely to have low mortality and therefore portend increased incidence of dementia.
| S-EPMC6252289 | biostudies-literature