The low dimensionality of post-stroke cognitive deficits: it's the lesion anatomy!

For years, dissociation studies on neurological single-case patients with brain lesions were the dominant method to infer fundamental cognitive functions in neuropsychology. In contrast, the association between deficits was considered to be of less epistemological value. Still, associational computational methods for dimensionality reduction-such as principal component analysis or factor analysis-became popular for the identification of fundamental cognitive functions and to understand human cognitive brain architecture from post-stroke neuropsychological profiles. In the present in silico study with lesion imaging of 300 stroke patients, we investigated the dimensionality of artificial simulated neuropsychological profiles that exclusively contained independent fundamental cognitive functions without any underlying low-dimensional cognitive architecture. Still, the anatomy of stroke lesions alone was sufficient to create a dependence between variables that allowed a low-dimensional description of the data with principal component analysis. All criteria that we used to estimate the dimensionality of data, including the Kaiser criterion, were strongly affected by lesion anatomy, while the Joliffe criterion provided the least affected estimates. The dimensionality of profiles was reduced by 62-70% for the Kaiser criterion, up to the degree that is commonly found in neuropsychological studies on actual cognitive measures. The interpretability of such low-dimensional factors as deficits of fundamental cognitive functions and their provided insights into human cognitive architecture thus seem to be severely limited, and the heavy focus of current cognitive neuroscience on group studies and associations calls for improvements. We suggest that qualitative criteria and dissociation patterns could be used to refine estimates for the dimensionality of the cognitive architecture behind post-stroke deficits. Further, given the strong impact of lesion anatomy on the associational structure of data, we see the need for further optimization of interpretation strategies of computational factors in post-stroke lesion studies of cognitive deficits.

Cerebral small vessel disease and stroke: Linked by stroke aetiology, but not stroke lesion location or size.

BACKGROUND: Cerebral small vessel disease (SVD) has previously been associated with worse stroke outcome, vascular dementia, and specific post-stroke cognitive deficits. The underlying causal mechanisms of these associations are not yet fully understood. We investigated whether a relationship between SVD and certain stroke aetiologies or a specific stroke lesion anatomy provides a potential explanation. METHODS: In a retrospective observational study, we examined 859 patients with first-ever, non-SVD anterior circulation ischemic stroke (age = 69.0±15.2). We evaluated MRI imaging markers to assess an SVD burden score and mapped stroke lesions on diffusion-weighted MRI. We investigated the association of SVD burden with i) stroke aetiology, and ii) lesion anatomy using topographical statistical mapping. RESULTS: With increasing SVD burden, stroke of cardioembolic aetiology was more frequent (ρ = 0.175; 95 %-CI = 0.103;0.244), whereas cervical artery dissection (ρ = -0.143; 95 %-CI = -0.198;-0.087) and a patent foramen ovale (ρ = -0.165; 95 %-CI = -0.220;-0.104) were less frequent stroke etiologies. However, no significant associations between SVD burden and stroke aetiology remained after additionally controlling for age (all p>0.125). Lesion-symptom-mapping and Bayesian statistics showed that SVD burden was not associated with a specific stroke lesion anatomy or size. CONCLUSIONS: In patients with a high burden of SVD, non-SVD stroke is more likely to be caused by cardioembolic aetiology. The common risk factor of advanced age may link both pathologies and explain some of the existing associations between SVD and stroke. The SVD burden is not related to a specific stroke lesion location.

Bayesian lesion-deficit inference with Bayes factor mapping: Key advantages, limitations, and a toolbox.

Statistical lesion-symptom mapping is largely dominated by frequentist approaches with null hypothesis significance testing. They are popular for mapping functional brain anatomy but are accompanied by some challenges and limitations. The typical analysis design and the structure of clinical lesion data are linked to the multiple comparison problem, an association problem, limitations to statistical power, and a lack of insights into evidence for the null hypothesis. Bayesian lesion deficit inference (BLDI) could be an improvement as it collects evidence for the null hypothesis, i.e. the absence of effects, and does not accumulate α-errors with repeated testing. We implemented BLDI by Bayes factor mapping with Bayesian t-tests and general linear models and evaluated its performance in comparison to frequentist lesion-symptom mapping with a permutation-based family-wise error correction. We mapped the voxel-wise neural correlates of simulated deficits in an in-silico-study with 300 stroke patients, and the voxel-wise and disconnection-wise neural correlates of phonemic verbal fluency and constructive ability in 137 stroke patients. Both the performance of frequentist and Bayesian lesion-deficit inference varied largely across analyses. In general, BLDI could find areas with evidence for the null hypothesis and was statistically more liberal in providing evidence for the alternative hypothesis, i.e. the identification of lesion-deficit associations. BLDI performed better in situations in which the frequentist method is typically strongly limited, for example with on average small lesions and in situations with low power, where BLDI also provided unprecedented transparency in terms of the informative value of the data. On the other hand, BLDI suffered more from the association problem, which led to a pronounced overshoot of lesion-deficit associations in analyses with high statistical power. We further implemented a new approach to lesion size control, adaptive lesion size control, that, in many situations, was able to counter the limitations imposed by the association problem, and increased true evidence both for the null and the alternative hypothesis. In summary, our results suggest that BLDI is a valuable addition to the method portfolio of lesion-deficit inference with some specific and exclusive advantages: it deals better with smaller lesions and low statistical power (i.e. small samples and effect sizes) and identifies regions with absent lesion-deficit associations. However, it is not superior to established frequentist approaches in all respects and therefore not to be seen as a general replacement. To make Bayesian lesion-deficit inference widely accessible, we published an R toolkit for the analysis of voxel-wise and disconnection-wise data.

Association of diabetes mellitus and admission glucose levels with outcome after endovascular therapy in acute ischaemic stroke in anterior circulation.

BACKGROUND AND PURPOSE: We aimed to assess the association of diabetes mellitus (DM) and admission hyperglycaemia (AH), respectively, and outcome in patients with acute ischaemic stroke with large vessel occlusion in the anterior circulation treated with endovascular therapy (EVT) in daily clinical practice. METHODS: Consecutive EVT patients admitted to our stroke centre between February 2015 and April 2020 were included in this observational cohort study. Patients with versus without DM and with versus without AH (glucose ≥ 7.8 mmol/L) were compared. RESULTS: We included 1020 patients (48.9% women, median age = 73.1 years); 282 (27.6%) had DM, and 226 (22.2%) had AH. Patients with versus without DM less often showed successful reperfusion (odds ratio [OR]adjusted  = 0.61, p = 0.023) and worse 3-month functional outcome (modified Rankin Scale [mRS] = 0-2: 31.3% vs. 48%, ORadjusted  = 0.59, p = 0.004; death: 38.9% vs. 24.1%, ORadjusted  = 1.75, p = 0.002; mRS shift: padjusted  < 0.0001; if moderate/good collaterals and mismatch, mRS = 0-2: ORadjusted  = 0.52, p = 0.005; death: ORadjusted  = 1.95, p = 0.005). If analysis was additionally adjusted for AH, only mRS shift was still significantly worse in patients with DM (padjusted  = 0.012). Patients with versus without AH showed similar successful reperfusion rates and worse 3-month functional outcome (mRS = 0-2: 28.3% vs. 50.4%, ORadjusted  = 0.52, p < 0.0001; death: 40.4% vs. 22.4%, ORadjusted  = 1.80, p = 0.001; mRS shift: padjusted  < 0.0001; if moderate/good collaterals and mismatch, mRS = 0-2: ORadjusted  = 0.38, p < 0.0001; death: ORadjusted  = 2.39, p < 0.0001). If analysis was additionally adjusted for DM, 3-month functional outcome remained significantly worse in patients with AH (mRS = 0-2: ORadjusted  = 0.58, p = 0.004; death: ORadjusted  = 1.57, p = 0.014; mRS shift: padjusted  = 0.004). DM independently predicted recurrent/progressive in-hospital ischaemic stroke (OR = 1.71, p = 0.043) together with admission National Institutes of Health Stroke Scale score (OR = 0.95, p = 0.005), and AH independently predicted in-hospital symptomatic intracranial haemorrhage (OR = 2.21, p = 0.001). The association of admission continuous glucose levels and most outcome variables was (inversely) J-shaped. CONCLUSIONS: Hyperglycaemia more than DM was associated with worse 3-month outcome in the patients studied, more likely so in the case of moderate/good collaterals and mismatch in admission imaging.

[Post-stroke cognitive deficits and dementia]. / Kognitive Defizite und Demenz nach Schlaganfall.

Post-stroke cognitive deficits and dementia Abstract. Prediction of stroke outcome remains challenging due to a large inter-individual variability. For a long time, research on stroke outcome has been mainly confined to post-stroke motor deficits, whereas post-stroke cognitive decline has been less investigated though being an often reason for dependency and disability. Post-stroke cognitive impairment demonstrate high inter-individual variability, which is expected to increase further due to the increasing life expectancy and number of patients with pre-stroke brain pathology and cognitive deficits. There exist different types and patterns of post-stroke cognitive impairment: i) the deficits in one or several cognitive domains meaning the variability in neuropsychological profiles; ii) the decline might vary from mild to manifested dementia comprising a wide spectrum in severity; iii) with occurrence immediately after stroke or with delayed manifestation several months later without obvious reasons. Patients at risk for post-stroke cognitive impairment cannot be reliably identified. Many factors have been shown to worsen post-stroke cognitive outcome, but their effects have been only investigated in isolation by ignoring their potential interactions. An overall model sufficiently predicting post-stroke cognitive outcome was therefore missing until now. We recently suggested that the concepts of brain reserve and cognitive reserve, which are established for neurodegeneration, may represent a valuable theoretical framework to predict stroke-induced cognitive decline and disability. Cognitive stroke outcome can be defined as a result of an interaction between brain reserve (e. g. brain volume), cognitive reserve (e. g. level of education, cognitive-stimulation leisure activities) and lesion load. Our recent findings supported this hypothesis also for functional stroke outcome. By representing a valuable model comprehensively incorporating an individual's characteristics, the concepts of brain and cognitive reserve might help in screening of risk patients, establishment of individualized therapeutic approaches, and enable knowledge transfer.

Predictors and signatures of recovery from neglect in acute stroke.

OBJECTIVE: Spatial neglect can either spontaneously resolve or persist after stroke; the latter is associated with a poorer outcome. We aimed to investigate the neural correlates and predictors of favorable versus poor recovery from neglect in acute stroke. METHODS: In addition to neuropsychological testing, we explored task-related functional magnetic resonance imaging activation and functional connectivity in 34 patients with neglect and/or extinction. Patients were examined at 2 to 3 days (acute phase I) and 8 to 10 days (acute phase II), and some of them at 4 to 6 months (chronic phase) poststroke. RESULTS: Course of recovery was predicted by the strength of functional connectivity between the right parietal and left prefrontal and parietal regions, as early as acute phase I. During acute phase II, favorable recovery from neglect was associated with increased activation in the left prefrontal and right parietal regions, an effect not observed at any time point in patients with poor acute recovery. The extent of neglect amelioration correlated with activation gain in the right attention centers; stronger activation of their left functional homologues correlated with better spatial processing in the neglected hemispace during both of the acute examination phases. INTERPRETATION: System excitability and early recruitment of contralesional functional homologues represented specific features of favorable recovery in acute stroke. In severe strokes leading to neglect, contralesional functional homologues support recovery by modulating the preserved ipsilesional network, and initial functional connectivity between them might predict recovery course and help to identify patients with potentially poor recovery requiring more intensive early rehabilitation.

Visual neglect after left-hemispheric lesions: a voxel-based lesion-symptom mapping study in 121 acute stroke patients.

Visual neglect after left-hemispheric lesion is thought to be less frequent, less severe, and shorter lived than visuospatial attention deficits resulting from right-hemispheric lesions. However, reports exist opposing this assumption, and it is unclear how these findings fit into the current theories of visuospatial processing. Furthermore, only little is known about the exact structure-function relationship between visuospatial attention deficits and left-hemispheric stroke. We investigated neglect in 121 patients with acute left-hemispheric ischemic stroke by following clinical development from within the first 24 h of stroke onset until hospital discharge. Visuospatial attention deficits occurred in 17.4 % (n = 21). Voxel-based lesion-symptom mapping associated visual neglect to the right with lesion in the left superior and middle temporal gyrus, temporal pole, frontal operculum, and insula. Neglect severity, captured by the Center of Cancellation Score of the Bells test, was associated with lesion in the left anterior temporal lobe and the left frontal operculum. The left-hemispheric lesion pattern of neglect thus involves areas of the ventral attention system and partly mirrors the critical regions of the right hemisphere known to be associated with neglect. Based on our prospective analysis on a large cohort of patients with left-hemispheric stroke, this study shows that in a remarkable number of patients, the left hemisphere essentially contributes to an intact representation of space and clarifies the impact of the distinct left-hemispheric structures involved in visuospatial processing.

Differential Roles of Ventral and Dorsal Streams for Conceptual and Production-Related Components of Tool Use in Acute Stroke Patients.

Impaired tool use despite preserved basic motor functions occurs after stroke in the context of apraxia, a cognitive motor disorder. To elucidate the neuroanatomical underpinnings of different tool use deficits, prospective behavioral assessments of 136 acute left-hemisphere stroke patients were combined with lesion delineation on magnetic resonance imaging (MRI) images for voxel-based lesion-symptom mapping. Deficits affecting both the selection of the appropriate recipient for a given tool (ToolSelect, e.g., choosing the nail for the hammer), and the performance of the typical tool-associated action (ToolUse, e.g., hammering in the nail) were associated with ventro-dorsal stream lesions, particularly within inferior parietal lobule. However, ToolSelect compared with ToolUse deficits were specifically related to damage within ventral stream regions including anterior temporal lobe. Additional retrospective error dichotomization based on the videotaped performances of ToolUse revealed that spatio-temporal errors (movement errors) were mainly caused by inferior parietal damage adjacent to the intraparietal sulcus while content errors, that is, perplexity, unrecognizable, or semantically incorrect movements, resulted from lesions within supramarginal gyrus and superior temporal lobe. In summary, our results suggest that in the use of tools, conceptual and production-related aspects can be differentiated and are implemented in anatomically distinct streams.

Predicting planning performance from structural connectivity between left and right mid-dorsolateral prefrontal cortex: moderating effects of age during postadolescence and midadulthood.

Complex cognitive abilities such as planning are known to critically rely on activity of bilateral mid-dorsolateral prefrontal cortex (mid-dlPFC). However, the functional relevance of the structural connectivity between left and right mid-dlPFC is yet unknown. Here, we applied global tractography to derive streamline counts as estimates of the structural connectivity between mid-dlPFC homologs and related it to planning performance in the Tower of London task across early to midadulthood, assuming a moderating effect of age. Multiple regression analyses with interaction effects revealed that streamline counts between left and right mid-dlPFC were negatively associated with planning performance specifically in early postadolescence. From the fourth life decade on, there was a trend for a reversed, positive association. These differential findings were corroborated by converging results from fractional anisotropy and white-matter density estimates in the genu of the corpus callosum where fibers connecting mid-dlPFC homologs traversed. Moreover, the results for streamline counts were regionally specific, marking the strength of mid-dlPFC connectivity as critical in predicting interindividual differences in planning performance across different stages of adulthood. Taken together, present findings provide first evidence for nonadditive effects of age on the relation between complex cognitive abilities and the structural connectivity of mid-dlPFC homologs.

A single dual-stream framework for syntactic computations in music and language.

This study is the first to compare in the same subjects the specific spatial distribution and the functional and anatomical connectivity of the neuronal resources that activate and integrate syntactic representations during music and language processing. Combining functional magnetic resonance imaging with functional connectivity and diffusion tensor imaging-based probabilistic tractography, we examined the brain network involved in the recognition and integration of words and chords that were not hierarchically related to the preceding syntax; that is, those deviating from the universal principles of grammar and tonal relatedness. This kind of syntactic processing in both domains was found to rely on a shared network in the left hemisphere centered on the inferior part of the inferior frontal gyrus (IFG), including pars opercularis and pars triangularis, and on dorsal and ventral long association tracts connecting this brain area with temporo-parietal regions. Language processing utilized some adjacent left hemispheric IFG and middle temporal regions more than music processing, and music processing also involved right hemisphere regions not activated in language processing. Our data indicate that a dual-stream system with dorsal and ventral long association tracts centered on a functionally and structurally highly differentiated left IFG is pivotal for domain-general syntactic competence over a broad range of elements including words and chords.

The ventral fiber pathway for pantomime of object use.

The current concept of a dual loop system of brain organization predicts a domain-general dual-pathway architecture involving dorsal and ventral fiber connections. We investigated if a similar dichotomy of brain network organization applies for pantomime (P) and imitation of meaningless gestures (I). Impairments of these tasks occur after left hemispheric brain lesions causing apraxia. Isolated impairments and double-dissociations point towards an anatomical segregation. Frontal and parietal areas seem to contribute differently. A special role of the inferior frontal gyrus and underlying fiber pathways was suggested recently. Using a combined fMRI/DTI-approach, we compared the fiber pathway architecture of left hemispheric frontal, temporal and parietal network components of pantomime and imitation. Thereby, we separated object effects from pantomime-specific effects. P and I both engage a fronto-temporo-parietal network of cortical areas interconnected by a dorsal fiber system (superior longitudinal fascicle) for direct sensory-motor interactions. The pantomime-specific effect additionally involved the triangular part of the inferior frontal gyrus, the middle temporal gyrus, the inferior parietal cortex and the intraparietal sulcus, interconnected by ventral fibers of the extreme capsule, likely related to higher-order conceptual and semantic operations. We discuss this finding in the context of the dual loop model and recent anatomical concepts.

Fiber pathways connecting cortical areas relevant for spatial orienting and exploration.

By implementing a task that closely resembled a clinical test for diagnosing spatial neglect in stroke patients, Himmelbach et al. (: Neuroimage 32:1747-1759) found significantly increased activation during active exploration in those cortical areas in healthy subjects that are known to induce spatial neglect in case of a lesion. The present study investigated whether direct intra-hemispheric cortico-cortical connections could be found between these activated clusters using a probabilistic fiber-tracking approach in 52 healthy subjects. We found that parts of the extreme capsule (EmC) and the middle longitudinal fascicle (MdLF) connected the functional cluster in the prefrontal cortex with the superior temporal cortex and the temporo-parietal junction (TPJ) area in both hemispheres. The activation peak in the TPJ was additionally connected to the inferior frontal cortex by parts of the arcuate fascicle and the superior longitudinal fascicle (SLF II) in the right hemisphere. Our study elucidates the connections constituting the perisylvian network for spatial orienting and attention. Hence, we complement the knowledge from patients suffering from spatial neglect by giving first empirical evidence for the complete postulated network in healthy subjects.

Attention-network specific alterations of structural connectivity in the undamaged white matter in acute neglect.

Visual neglect results from dysfunction within the spatial attention network. The structural connectivity in undamaged brain tissue in neglect has barely been investigated until now. In the present study, we explored the microstructural white matter characteristics of the contralesional hemisphere in relation to neglect severity and recovery in acute stroke patients. We compared age-matched healthy subjects and three groups of acute stroke patients (9 ± 0.5 days after stroke): (i) patients with nonrecovered neglect (n = 12); (ii) patients with rapid recovery from initial neglect (within the first week post-stroke, n = 7), (iii) stroke patients without neglect (n = 17). We analyzed the differences between groups in grey and white matter density and fractional anisotropy (FA) and used fiber tracking to identify the affected fibers. Patients with nonrecovered neglect differed from those with rapid recovery by FA-reduction in the left inferior parietal lobe. Fibers passing through this region connect the left-hemispheric analogues of the ventral attention system. Compared with healthy subjects, neglect patients with persisting neglect had FA-reduction in the left superior parietal lobe, optic radiation, and left corpus callosum/cingulum. Fibers passing through these regions connect centers of the left dorsal attention system. FA-reduction in the identified regions correlated with neglect severity. The study shows for the first time white matter changes within the spatial attention system remote from the lesion and correlating with the extent and persistence of neglect. The data support the concept of neglect as disintegration within the whole attention system and illustrate the dynamics of structural-functional correlates in acute stroke.

Multivariate mapping of brain pathology: a step forward with stumbling blocks.

This scientific commentary refers to 'Ground-truth validation of uni- and multivariate lesion inference approaches', by Zavaglia et al. (https://doi.org/10.1093/braincomms/fcae251).

Improving diagnostic accuracy of the Montreal Cognitive Assessment to identify post-stroke cognitive impairment.

Given advantages in reperfusion therapy leading to mild stroke, less apparent cognitive deficits can be overseen in a routine neurological examination. Despite the widespread use of the Montreal Cognitive Assessment (MoCA), age- and education-specific cutoffs for the detection of post-stroke cognitive impairment (PSCI) are not established, hampering its valid application in stroke. We aimed to establish age- and education-specific MoCA cutoffs to better discriminate patients with and without acute PSCI. Patients with acute ischemic stroke underwent the MoCA and a detailed neuropsychological assessment. PSCI was defined as a performance < - 1.5 SD in ≥ 2 cognitive domains. As secondary data analysis, the discriminant abilities of the MoCAraw-score (not adding + 1 as correction for ≤ 12 years of education, YoE) cutoffs were automatically derived based on Youden Index and evaluated by receiver operating characteristic analyses across age- (< 55, 55-70, > 70 years old) and education-specific (≤ 12 and > 12 YoE) groups. 351 stroke patients (67.4 ± 14.1 years old; 13.1 ± 2.8 YoE) underwent the neuropsychological assessment 2.7 ± 2.0 days post-stroke. The original MoCA cutoff < 26 falsely classified 26.2% of examined patients, with poor sensitivity in younger adults (34.8% in patients < 55 years > 12 YoE) and poor specificity in older adults (55.0%, in > 70 years ≤ 12 YoE). By maximizing both sensitivity and specificity, the optimal MoCAraw cutoffs were: (i) < 28 in patients aged < 55 with > 12 YoE (sensitivity = 69.6%, specificity = 77.8%); (ii) < 22 and < 25 in patients > 70 years with ≤ 12 and > 12 YoE (sensitivity = 61.6%, specificity = 90.0%; sensitivity = 63.3%, specificity = 84.0%, respectively). In other groups the optimal MoCAraw cutoff was < 26. Age and education level should be considered when interpreting MoCA-scores. Though new age- and education-specific cutoffs demonstrated higher discriminant ability for PSCI, their performance in young stroke and adults with higher education level was low due to ceiling effects and MoCA subtests structure, and cautious interpretation in these patients is warranted.Trial registration: ClinicalTrials.gov Identifier: NCT05653141.

Adaptation of the Concept of Brain Reserve for the Prediction of Stroke Outcome: Proxies, Neural Mechanisms, and Significance for Research.

The prediction of stroke outcome is challenging due to the high inter-individual variability in stroke patients. We recently suggested the adaptation of the concept of brain reserve (BR) to improve the prediction of stroke outcome. This concept was initially developed alongside the one for the cognitive reserve for neurodegeneration and forms a valuable theoretical framework to capture high inter-individual variability in stroke patients. In the present work, we suggest and discuss (i) BR-proxies-quantitative brain characteristics at the time stroke occurs (e.g., brain volume, hippocampus volume), and (ii) proxies of brain pathology reducing BR (e.g., brain atrophy, severity of white matter hyperintensities), parameters easily available from a routine MRI examination that might improve the prediction of stroke outcome. Though the influence of these parameters on stroke outcome has been partly reported individually, their independent and combined impact is yet to be determined. Conceptually, BR is a continuous measure determining the amount of brain structure available to mitigate and compensate for stroke damage, thus reflecting individual differences in neural resources and a capacity to maintain performance and recover after stroke. We suggest that stroke outcome might be defined as an interaction between BR at the time stroke occurs and lesion load. BR in stroke can potentially be influenced, e.g., by modifying cardiovascular risk factors. In addition to the potential power of the BR concept in a mechanistic understanding of inter-individual variability in stroke outcome and establishing individualized therapeutic approaches, it might help to strengthen the synergy of preventive measures in stroke, neurodegeneration, and healthy aging.

Post-stroke cognitive impairment remains highly prevalent and disabling despite state-of-the-art stroke treatment.

BACKGROUND: State-of-the-art stroke treatment significantly reduces lesion size and stroke severity, but it remains unclear whether these therapeutic advances have diminished the burden of post-stroke cognitive impairment (PSCI). AIMS: In a cohort of patients receiving modern state-of-the-art stroke care including endovascular therapy, we assessed the frequency of PSCI and the pattern of domain-specific cognitive deficits, identified risk factors for PSCI, and determined the impact of acute PSCI on stroke outcome. METHODS: In this prospective monocentric cohort study, we examined patients with first-ever anterior circulation ischemic stroke without pre-stroke cognitive decline, using a comprehensive neuropsychological assessment ⩽10 days after symptom onset. Normative data were stratified by demographic variables. We defined PSCI as at least moderate (<1.5 standard deviation) deficits in ⩾2 cognitive domains. Multivariable regression analysis was applied to define risk factors for PSCI. RESULTS: We analyzed 329 non-aphasic patients admitted from December 2020 to July 2023 (67.2 ± 14.4 years old, 41.3% female, 13.1 ± 2.7 years of education). Although most patients had mild stroke (median National Institutes of Health Stroke Scale (NIHSS) 24 h = 1.00 (0.00; 3.00); 87.5% with NIHSS ⩽ 5), 69.3% of them presented with PSCI 2.7 ± 2.0 days post-stroke. The most severely and often affected cognitive domains were verbal learning, episodic memory, executive functions, selective attention, and constructive abilities (39.1%-51.2% of patients), whereas spatial neglect was less frequent (18.5%). The risk of PSCI was reduced with more years of education (odds ratio (OR) = 0.47, 95% confidence interval (CI) = 0.23-0.99) and right hemisphere lesions (OR = 0.47, 95% CI = 0.26-0.84), and increased with stroke severity (NIHSS 24 h, OR = 4.19, 95% CI = 2.72-6.45), presence of hyperlipidemia (OR = 1.93, 95% CI = 1.01-3.68), but was not influenced by age. After adjusting for stroke severity and depressive symptoms, acute PSCI was associated with poor functional outcome (modified Rankin Scale > 2, F = 13.695, p < 0.001) and worse global cognition (Montreal Cognitive Assessment (MoCA) score, F = 20.069, p < 0.001) at 3 months post-stroke. CONCLUSION: Despite modern stroke therapy and many strokes having mild severity, PSCI in the acute stroke phase remains frequent and associated with worse outcome. The most prevalent were learning and memory deficits. Cognitive reserve operationalized as years of education independently protects post-stroke cognition.

The analysis of association between single features of small vessel disease and stroke outcome shows the independent impact of the number of microbleeds and presence of lacunes.

The impact of small vessel disease (SVD) on stroke outcome was investigated either separately for its single features in isolation or for SVD sum score measuring a qualitative (binary) assessment of SVD-lesions. We aimed to investigate which SVD feature independently impacts the most on stroke outcome and to compare the continuous versus binary SVD assessment that reflects pronouncement and presence correspondingly. Patients with a first-ever anterior circulation ischemic stroke were retrospectively investigated. We performed an ordered logistic regression analysis to predict stroke outcome (mRS 3 months, 0-6) using age, stroke severity, and pre-stroke disability as baseline input variables and adding SVD-features (lacunes, microbleeds, enlarged perivascular spaces, white matter hyperintensities) assessed either continuously (model 1) or binary (model 2). The data of 873 patients (age 67.9 ± 15.4, NIHSS 24 h 4.1 ± 4.8) was analyzed. In model 1 with continuous SVD-features, the number of microbleeds was the only independent predictor of stroke outcome in addition to clinical parameters (OR 1.21; 95% CI 1.07-1.37). In model 2 with the binary SVD assessment, only the presence of lacunes independently improved the prediction of stroke outcome (OR 1.48, 1.1-1.99). In a post hoc analysis, both the continuous number of microbleeds and the presence of lacunes were independent significant predictors. Thus, the number of microbleeds evaluated continuously and the presence of lacunes are associated with stroke outcome independent from age, stroke severity, pre-stroke disability and other SVD-features. Whereas the presence of lacunes is adequately represented in SVD sum score, the microbleeds assessment might require another cutoff and/or gradual scoring, when prediction of stroke outcome is needed.