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Background:
Cognitive impairment and neuropsychiatric syndromes, like depression and apathy, are frequent residual consequences of stroke. These have a large impact on quality of life and long-term prognosis. Several factors are involved in the development of these residual syndromes, although their exact role and their interrelationships remain s...
Context in source publication
Context 1
... neuropsychological assessment consists of a stan- dardized battery of cognitive tests measuring specific cognitive domains: global cognition, episodic memory, working memory, information processing speed, execu- tive functioning, visuoconstruction, neglect, premorbid IQ, and language (dysphasia). An overview of all test in- struments and their cognitive domains is presented in Table 2. The neuropsychological tests are administered according to a standardized test protocol by trained re- search (neuro)psychologists. VCI is defined as a score ≤ 1.5 standard deviations below the general population mean in one or more cog- nitive domains, based on available norm scores for age, gender, and level of education for the Dutch general population. ...
Citations
... However, mechanisms behind vascular cognitive impairment are largely unknown. For this reason, numerous prospective observational studies are examining predictors of post-stroke cognitive decline [52][53][54][55][56][57][58] and consortia have been established to drive the research into vascular cognitive impairment forward [59,60]. With ENIGMA we hope to provide novel knowledge about the microvascular mechanisms behind PSCI and the potential of EVs as biomarkers of the vascular brain reserve and consequently post-stroke cognitive function. ...
Background
Post-stroke cognitive impairment (PSCI) is common. However, the underlying pathophysiology remains largely unknown. Understanding the role of microvascular changes and finding markers that can predict PSCI, could be a first step towards better screening and management of PSCI. Capillary dysfunction is a pathological feature of cerebral small vessel disease and may play a role in the mechanisms underlying PSCI. Extracellular vesicles (EVs) are secreted from cells and may act as disease biomarkers. We aim to investigate the role of capillary dysfunction in PSCI and the associations between EV characteristics and cognitive function one year after acute ischemic stroke (AIS) and transient ischemic attack (TIA).
Methods
The ENIGMA study is a single-centre prospective clinical observational study conducted at Aarhus University Hospital, Denmark. Consecutive patients with AIS and TIA are included and followed for one year with follow-up visits at three and 12 months. An MRI is performed at 24 h and 12 months follow-up. EV characteristics will be characterised from blood samples drawn at 24 h and three months follow-up. Cognitive function is assessed three and 12 months after AIS and TIA using the Repeatable Battery for the Assessment of Neuropsychological Status.
Discussion
Using novel imaging and molecular biological techniques the ENIGMA study will provide new knowledge about the vascular contributions to cognitive decline and dementia.
Trial registration
The study is retrospectively registered as an ongoing observational study at ClinicalTrials.gov with the identifier NCT06257823.
... Data and contributing studies Data were sourced from STROKOG (Stroke and Cognition Consortium), an international collaboration of observational stroke studies. 15 Nine STROKOG studies contributed data, including five conducted in Europe, [16][17][18][19][20] two in Asia, 21,22 one in Australia, 23 and one in the United States. 24 Detailed study information is provided in Table S1. ...
Aim
Recovery from stroke is adversely affected by neuropsychiatric complications, cognitive impairment, and functional disability. Better knowledge of their mutual relationships is required to inform effective interventions. Network theory enables the conceptualization of symptoms and impairments as dynamic and mutually interacting systems. We aimed to identify interactions of post‐stroke complications using network analysis in diverse stroke samples.
Methods
Data from 2185 patients were sourced from member studies of STROKOG, an international collaboration of stroke studies. Networks were generated for each cohort, whereby nodes represented neuropsychiatric symptoms, cognitive deficits, and disabilities on activities of daily living. Edges characterized associations between them. Centrality measures were used to identify hub items.
Results
Across cohorts, a single network of interrelated post‐stroke complications emerged. Networks exhibited dissociable depression, apathy, fatigue, cognitive impairment, and functional disability modules. Worry was the most central symptom across cohorts, irrespective of the depression scale used. Items relating to activities of daily living were also highly central nodes. Follow‐up analysis in two studies revealed that individuals who worried had more densely connected networks than those free of worry (CASPER study: S = 9.72, p = 0.038; Sydney Stroke Study: S = 13.56, p = 0.069).
Conclusion
Neuropsychiatric symptoms are highly interconnected with cognitive deficits and functional disabilities resulting from stroke. Given their central position and high level of connectedness, worry and activities of daily living have the potential to drive multimorbidity and mutual reinforcement between domains of post‐stroke complications. Targeting these factors early after stroke may have benefits that extend to other complications, leading to better stroke outcomes.
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... For the present study, we included those patients for whom baseline kynurenines in fasting plasma were quantified. The rationale and procedures of the study have previously been described in more detail elsewhere [21]. In short, the CAS-PER study is a prospective cohort study in patients after ischemic or hemorrhagic stroke who were admitted to the Stroke Unit of the Maastricht University Medical Center+ (MUMC+), the Stroke Unit of Zuyderland Medical Center, Sittard-Geleen, and Heerlen, or who visited the Transient Ischemic Attack clinic of MUMC+, the Netherlands. ...
... However, there is a paucity of comprehensive information regarding post-stroke HRQoL trajectories in young adult stroke survivors and therefore much of the variance of HRQoL after IS remains unexplained in this population. Existing literature reviews [1][2][3][4][5] and prospective cohort studies [30][31][32][33][34] provide information predominantly about the aetiology, risk factors and prognosis of IS in young adults. Moreover, most of the current understanding of the long-term consequences of IS comes from older populations [5]. ...
Purpose
To synthesize the body of knowledge on the factors influencing the quality of life (QoL) after ischemic stroke (IS) in young adults.
Methods
Guidelines regarding the scoping review methodology developed by the Joanna Briggs Institute, and the PRISMA-ScR checklist for a scoping review was used in this paper. A total of 1197 studies were identified through a bibliographic search in Web of Science, MEDLINE, PsycInfo, ScienceDirect, Scopus, and ProQuest Science Database. Articles published between the years 2000–2021 were included.
Results
A total of nine papers were finally selected to respond to the research question. Three studies were prospective longitudinal studies compared QoL between young stroke and age-matched controls from the general population. Across all the analysed studies, 14 variables potentially associated with QoL were identified. QoL in young patients is mainly affected by clinical outcomes after IS (scored by the modified Rankin scale and the Barthel index—favourable initial functional status and higher independence in ADL leads to higher QoL) and psychological factors (post-stroke fatigue and depression—higher levels of fatigue and depression lead to lower QoL). The reviewed studies emphasized the importance of functional outcomes, post-stroke depression, fatigue and anxiety and early return to work.
Conclusion
Further longitudinal studies are needed to identify the trajectory of post-stroke psychosocial symptoms over time and other potential predictors of unfavourable long-term QoL, thus specific young stroke rehabilitation and stroke self-management support programmes should be developed (address physical, psychological factors which influence the psychosocial adaptation post-stroke and the perception of the QoL).
... We selected patients from a recently published Meta VCI Map consortium project (Weaver et al., 2021) involving 2950 patients with ischemic stroke from 12 cohorts: France (GRECogVASC (Puy et al., 2018) and STROKDEM (Bournonville et al., 2018), Hong Kong (CU-STRIDE , the Netherlands (CASPER (Douven et al., 2016), CODECS , PROCRAS (Aben et al., 2018), and USCOG (Biesbroek et al., 2014), Singapore (COAST (Dong et al., 2012), South Korea (Bundang VCI (Yu et al., 2013;Lim et al., 2014) and Hallym VCI (Yu et al., 2013;Lim et al., 2014), and the UK (CROMIS-2 (Wilson et al., 2018) and MSS-2 (Wardlaw et al., 2017). For all cohorts, ethical and institutional approval were obtained as required by local regulations to allow data acquisition, including informed consent, and data sharing; details for each of the 12 individual cohort are provided in the cited design papers. ...
Background:
Post-stroke cognitive impairment (PSCI) is a common consequence of stroke. Accurate prediction of PSCI risk is challenging. The recently developed network impact score, which integrates information on infarct location and size with brain network topology, may improve PSCI risk prediction.
Aims:
To determine if the network impact score is an independent predictor of PSCI, and of cognitive recovery or decline.
Methods:
We pooled data from patients with acute ischemic stroke from 12 cohorts through the Meta VCI Map consortium. PSCI was defined as impairment in ≥ 1 cognitive domain on neuropsychological examination, or abnormal Montreal Cognitive Assessment. Cognitive recovery was defined as conversion from PSCI < 3 months post-stroke to no PSCI at follow-up, and cognitive decline as conversion from no PSCI to PSCI. The network impact score was related to serial measures of PSCI using Generalized Estimating Equations (GEE) models, and to PSCI stratified according to post-stroke interval (<3, 3-12, 12-24, >24 months) and cognitive recovery or decline using logistic regression. Models were adjusted for age, sex, education, prior stroke, infarct volume, and study site.
Results:
We included 2341 patients with 4657 cognitive assessments. PSCI was present in 398/844 patients (47%) <3 months, 709/1640 (43%) at 3-12 months, 243/853 (28%) at 12-24 months, and 208/522 (40%) >24 months. Cognitive recovery occurred in 64/181 (35%) patients and cognitive decline in 26/287 (9%). The network impact score predicted PSCI in the univariable (OR 1.50, 95%CI 1.34-1.68) and multivariable (OR 1.27, 95%CI 1.10-1.46) GEE model, with similar ORs in the logistic regression models for specified post-stroke intervals. The network impact score was not associated with cognitive recovery or decline.
Conclusions:
The network impact score is an independent predictor of PSCI. As such, the network impact score may contribute to a more precise and individualized cognitive prognostication in patients with ischemic stroke. Future studies should address if multimodal prediction models, combining the network impact score with demographics, clinical characteristics and other advanced brain imaging biomarkers, will provide accurate individualized prediction of PSCI. A tool for calculating the network impact score is freely available at https://metavcimap.org/features/software-tools/lsm-viewer/.
... In particular, it has been found that, after stroke, most of the patients may have enduring difficulties in specific cognitive domains, such as attention and concentration, memory, spatial awareness, perception, praxis, and executive functioning [9,10]. These cognitive impairments have a direct influence on patients' quality of life, being associated with greater rates of institutionalization and higher health care costs [11], and thus, reducing the impact of post-stroke cognitive impairment through appropriate rehabilitation programs is an essential goal. ...
Embodied cognition is a theoretical perspective that considers every form of human knowledge and cognition “embodied”, as they pass through bodily experience. The aim of this narrative review is to investigate the importance of mirror neurons system in EC, as well as the EC role in neurodegenerative diseases. This narrative review shows deep connections between body and mind: body states influence mental functions such as perception and reasoning, while mental states cause changes in the body, especially in neurodegenerative disorders. Indeed, abnormalities in EC were found in dementia, Parkinson’s Disease and Amyotrophic Lateral sclerosis, also in the absence of other cognitive deficits, negatively affecting patients’ outcomes. Exploiting EC mechanisms for rehabilitation purposes, also using innovation technologies, could be a promising therapeutic way to increase motor and cognitive outcomes in patients affected by different neurological disorders.
... After 3 months from the onset of a stroke, between 15-30% of stroke survivors have a permanent disability and 20% require institutional care [12]. Clinical and mental impairments following a stroke may include partial paralysis, memory, thinking, language, and movement difficulties [13,14]. ...
Strokes are very serious neurological disorders, most often with sudden onset, unpredictable evolution and very high mortality. According to the World Health Organization, about 15 million people survive a stroke each year, and 5-6 million die each year from it. Globally, strokes are one of the leading causes of morbidity and mortality. Relatively recent clinical data show that strokes are the second leading cause of death worldwide. Thus, in Europe, new strokes occur annually in 100-200 cases per 100,000 inhabitants. For Romania, the epidemiological analysis of the data of our study shows that strokes are the leading cause of death in vascular diseases, i.e. cerebrovascular and cardiovascular diseases put together.
... Apathy is a frequently occurring symptom after stroke a ecting around 30% of stroke patients (Van Dalen et al., 2013) and has been associated with cognitive impairments (Bickerton et al., 2015;Brodaty et al., 2013;Caeiro et al., 2013;Douven et al., 2018Douven et al., , 2016Hackett et al., 2014;Kennedy et al., 2015) and poor functional and rehabilitation outcome. (Harris et al., 2014;Kennedy et al., 2015;Matsuzaki et al., 2015;Skidmore et al., 2015;Van Dalen et al., 2013) Apathy is characterized by loss of motivation, interest and emotional responses, resulting in reduced initiative, interaction with the environment and social contacts. ...
... In one of the few prospective studies, levels of apathy increased over time in patients with relatively poor cognitive function at baseline. (Douven et al., 2016) The increase of apathy level in this study was most pronounced in patients with baseline impaired executive functioning and impaired information processing speed. (Douven et al., 2016) Most prospective studies have focused on cognition as predictor for apathy. ...
... (Douven et al., 2016) The increase of apathy level in this study was most pronounced in patients with baseline impaired executive functioning and impaired information processing speed. (Douven et al., 2016) Most prospective studies have focused on cognition as predictor for apathy. (Douven et al., 2018) Inversely; apathy may directly impact cognitive performance by reducing goal-directed thought, e ort and interest. ...
Apathy is common after stroke and has been associated with cognitive impairment. However, causality between post-stroke apathy and cognitive impairment remains unclear. We assessed the course of apathy in relation to changes in cognitive functioning in stroke survivors. Using the Apathy Scale (AS) and cognitive tests on memory, processing speed and executive functioning at six- and 15 months post-stroke we tested for associations between (1) AS-scores and (change in) cognitive scores; (2) apathy course (persistent/incident/resolved) and cognitive change scores. Of 117 included participants, 29% had persistent apathy, 13% apathy resolving over time and 10% apathy emerging between 6-15 months post-stroke. Higher AS-scores were cross-sectionally and longitudinally associated with lower cognitive scores. Relations between apathy and cognitive change scores were ambiguous. These inconsistent relations between apathy and changes in cognition over time suggest that post-stroke apathy does not directly impact cognitive performance. Both these sequelae of stroke require separate attention.
... Cognitive impairment after stroke can affect the quality of life and long-term prognosis (higher mortality and more disability) of stroke survivors [44]. Several studies have confirmed that the common functional single nucleotide polymorphism (SNP) in exon 12 of ALDH2 is a risk indicator for ischemic stroke [21]. ...
Aldehyde dehydrogenase 2 (ALDH2) polymorphisms are related to both stroke risk and alcohol consumption. However, the influence of ALDH2 polymorphisms and alcohol consumption on cognitive impairment after ischemic stroke remains unknown, as do the possible mechanisms. We enrolled 180 Han Chinese ischemic stroke patients from four community health centers in Bengbu, China. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), and two different MoCA cutoff scores were used to define cognitive impairment in ischemic stroke patients. The ALDH2 genotypes were determined using polymerase chain reaction and direct sequencing. To assess the associations of ALDH2 polymorphisms and alcohol consumption with cognitive impairment after ischemic stroke, we performed binary logistic regression analysis with odds ratios. We revealed that individuals with the ALDH2 wild-type genotype were more likely to have high MoCA scores than those with the mutant and heterozygous types (p=0.034). In addition, using two MoCA cutoff scores, the percentage of moderate to excessive alcohol consumption in the cognitive impairment group was higher than that in the nonimpairment group (p=0.001). The levels of 4-hydroxy-2-nonenal (p=0.001) and swallowing function (p=0.001) were also higher in the cognitive impairment group than in the nonimpairment group. Moreover, after adjusting for other potential risk factors, ALDH2 polymorphisms and alcohol consumption had a significant synergistic effect on cognitive impairment (p=0.022). Specifically, the ALDH2∗2 mutant allele and higher alcohol consumption were associated with cognitive impairment and swallowing ability after ischemic stroke. Targeting ALDH2 may be a useful biomarker for cognitive rehabilitation following ischemic stroke.
... We did a large-scale multicohort lesion-symptom mapping study, using pooled and harmonised individ ual patient data from 12 cohorts, from France (n=2; GRECogVASC 10 and STROKDEM 13 ), Hong Kong (n=1; CU-STRIDE 11 ), the Netherlands (n=4; CASPER, 14 CODECS, 12 PROCRAS, 15 and USCOG 16 ), Singapore (n=1; COAST 17 ), South Korea (n=2; Bundang VCI 18,19 and Hallym VCI 18,19 ), and the UK (n=2; CROMIS-2 20 and MSS-2 21 ). Eligible cohorts were identified (as of Jan 1, 2019) through the Meta VCI Map consortium's data index of member cohorts, via a search process described previously, 12 according to the following cri teria: a cohort of patients with acute ischaemic stroke; available brain CT or MRI (T1-weighted, T2-weighted, ...
... Both the continuous and 5-point variants of the location impact score were significantly associated with PSCI in the total dataset in our univariable model (table 2). This association was independent from other predictors in our multivariable model (appendix p 31). Leave-one-cohort-out cross-validation of the continuous and 5-point score (appendix pp [11][12][13][14] revealed good correspondence in terms of visual goodness of fit between predicted and observed risk in four well powered cohorts (Bundang VCI, CU-STRIDE, Hallym VCI, and PROCRAS) after adjusting the intercept for cohort-specific PSCI occurrence. C-statistics for these four cohorts ranged from 0·55 (95% CI 0·51-0·60) to 0·64 (0·57-0·71) and were similar for the continuous and 5-point scores (appendix pp [11][12][13][14]. ...
... This association was independent from other predictors in our multivariable model (appendix p 31). Leave-one-cohort-out cross-validation of the continuous and 5-point score (appendix pp [11][12][13][14] revealed good correspondence in terms of visual goodness of fit between predicted and observed risk in four well powered cohorts (Bundang VCI, CU-STRIDE, Hallym VCI, and PROCRAS) after adjusting the intercept for cohort-specific PSCI occurrence. C-statistics for these four cohorts ranged from 0·55 (95% CI 0·51-0·60) to 0·64 (0·57-0·71) and were similar for the continuous and 5-point scores (appendix pp [11][12][13][14]. Five other cohorts (CASPER, COAST, CROMIS-2, STROKDEM, and USCOG) showed a similar trend, but they provided less stable estimates, most prob ably due to limited sample size or low PSCI occur rence. ...
Background:
Post-stroke cognitive impairment (PSCI) occurs in approximately half of people in the first year after stroke. Infarct location is a potential determinant of PSCI, but a comprehensive map of strategic infarct locations predictive of PSCI is unavailable. We aimed to identify infarct locations most strongly predictive of PSCI after acute ischaemic stroke and use this information to develop a prediction model.
Methods:
In this large-scale multicohort lesion-symptom mapping study, we pooled and harmonised individual patient data from 12 cohorts through the Meta-analyses on Strategic Lesion Locations for Vascular Cognitive Impairment using Lesion-Symptom Mapping (Meta VCI Map) consortium. The identified cohorts (as of Jan 1, 2019) comprised patients with acute symptomatic infarcts on CT or MRI (with available infarct segmentations) and a cognitive assessment up to 15 months after acute ischaemic stroke onset. PSCI was defined as performance lower than the fifth percentile of local normative data, on at least one cognitive domain on a multidomain neuropsychological assessment or on the Montreal Cognitive Assessment. Voxel-based lesion-symptom mapping (VLSM) was used to calculate voxel-wise odds ratios (ORs) for PSCI that were mapped onto a three-dimensional brain template to visualise PSCI risk per location. For the prediction model of PSCI risk, a location impact score on a 5-point scale was derived from the VLSM results on the basis of the mean voxel-wise coefficient (ln[OR]) within each patient's infarct. We did combined internal-external validation by leave-one-cohort-out cross-validation for all 12 cohorts using logistic regression. Predictive performance of a univariable model with only the location impact score was compared with a multivariable model with addition of other clinical PSCI predictors (age, sex, education, time interval between stroke onset and cognitive assessment, history of stroke, and total infarct volume). Testing of visual ratings was done by three clinicians, and accuracy, inter-rater reliability, and intra-rater reliability were assessed with Cohen's weighted kappa.
Findings:
In our sample of 2950 patients (mean age 66·8 years [SD 11·6]; 1157 [39·2%] women), 1286 (43·6%) had PSCI. We achieved high lesion coverage of the brain in our analyses (86·9%). Infarcts in the left frontotemporal lobes, left thalamus, and right parietal lobe were strongly associated with PSCI (after false discovery rate correction, q<0·01; voxel-wise ORs >20). On cross-validation, the location impact score showed good correspondence, based on visual assessment of goodness of fit, between predicted and observed risk of PSCI across cohorts after adjusting for cohort-specific PSCI occurrence. Cross-validations showed that the location impact score by itself had similar performance to the combined model with other PSCI predictors, while allowing for easy visual assessment. Therefore the univariable model with only the location impact score was selected as the final model. Correspondence between visual ratings and actual location impact score (Cohen's weighted kappa: range 0·88-0·92), inter-rater agreement (0·85-0·87), and intra-rater agreement (for a single rater, 0·95) were all high.
Interpretation:
To the best of our knowledge, this study provides the first comprehensive map of strategic infarct locations associated with risk of PSCI. A location impact score was derived from this map that robustly predicted PSCI across cohorts. Furthermore, we developed a quick and reliable visual rating scale that might in the future be applied by clinicians to identify individual patients at risk of PSCI.
Funding:
The Netherlands Organisation for Health Research and Development.
