Disentangling poststroke cognitive deficits and their neuroanatomical correlates through combined multivariable and multioutcome lesion-symptom mapping.

Studies in patients with brain lesions play a fundamental role in unraveling the brain's functional anatomy. Lesion-symptom mapping (LSM) techniques can relate lesion location to cognitive performance. However, a limitation of current LSM approaches is that they can only evaluate one cognitive outcome at a time, without considering interdependencies between different cognitive tests. To overcome this challenge, we implemented canonical correlation analysis (CCA) as combined multivariable and multioutcome LSM approach. We performed a proof-of-concept study on 1075 patients with acute ischemic stroke to explore whether addition of CCA to a multivariable single-outcome LSM approach (support vector regression) could identify infarct locations associated with deficits in three well-defined verbal memory functions (encoding, consolidation, retrieval) based on four verbal memory subscores derived from the Seoul Verbal Learning Test (immediate recall, delayed recall, recognition, learning ability). We evaluated whether CCA could extract cognitive score patterns that matched prior knowledge of these verbal memory functions, and if these patterns could be linked to more specific infarct locations than through single-outcome LSM alone. Two of the canonical modes identified with CCA showed distinct cognitive patterns that matched prior knowledge on encoding and consolidation. In addition, CCA revealed that each canonical mode was linked to a distinct infarct pattern, while with multivariable single-outcome LSM individual verbal memory subscores were associated with largely overlapping patterns. In conclusion, our findings demonstrate that CCA can complement single-outcome LSM techniques to help disentangle cognitive functions and their neuroanatomical correlates.

Validation of the Short Form of Korean-Everyday Cognition (K-ECog).

BACKGROUND: Evaluating the activities of daily living (ADL) is an important factor for diagnosing dementia. The Everyday Cognition (ECog) scale was developed to measure ADL changes that were correlated with specific neuropsychological impairments. A short form of the ECog (ECog-12) was also developed, consisting of 12 items, two from each of the six cognitive domains of the ECog. The Korean full version of ECog (K-ECog) has recently been standardized, but the need for a shortened version has been raised in clinical practice. The purpose of this study was to develop a Korean version of ECog-12 (K-ECog-12) and to verify its reliability and validity by comparing those to the full version of K-ECog. METHODS: The participants were 267 cognitively normal older adults (CN), 183 patients with mild cognitive impairment (MCI), and 89 patients with dementia. The Korean-Mini Mental State Examination (K-MMSE), Korean-Montreal Cognitive Assessment (K-MoCA), and Short form of Geriatric Depression Scale (SGDS) were administered to all participants. The K-ECog and Korean-Instrumental Activities of Daily Living (K-IADL) were rated by the informants of patients. RESULTS: K-ECog-12 was newly constructed by replacing one item for the visuospatial function in the original ECog-12 with another one through an item response theory analysis on Korean data. The internal consistencies (Cronbach's α) of K-ECog-12 and K-ECog were 0.95 and 0.99, respectively. The test-retest reliabilities (Pearson's r) were 0.67 for K-ECog-12 and 0.73 for K-ECog. The K-ECog-12 was significantly correlated with K-ECog as well as K-IADL, K-MMSE, and K-MoCA. The K-ECog-12 scores differed significantly between the CN, MCI, and dementia groups, as did the K-ECog scores. Receiver operating characteristic curve analyses showed that K-ECog-12, like K-ECog, could differentiate MCI and dementia patients from CN as well. CONCLUSION: The K-ECog-12 is as reliable and valid as the K-ECog in assessing ADL. Therefore, K-ECog-12 can be used as an alternative to the K-ECog in clinical and community settings in Korea.

Long-Term Cognitive Decline After Stroke: An Individual Participant Data Meta-Analysis.

BACKGROUND: Poststroke cognitive impairment is common, but the trajectory and magnitude of cognitive decline after stroke is unclear. We examined the course and determinants of cognitive change after stroke using individual participant data from the Stroke and Cognition Consortium. METHODS: Nine longitudinal hospital-based cohorts from 7 countries were included. Neuropsychological test scores and normative data were used to calculate standardized scores for global cognition and 5 cognitive domains. One-step individual participant data meta-analysis was used to examine the rate of change in cognitive function and risk factors for cognitive decline after stroke. Stroke-free controls were included to examine rate differences. Based on the literature and our own data that showed short-term improvement in cognitive function after stroke, key analyses were restricted to the period beginning 1-year poststroke to focus on its long-term effects. RESULTS: A total of 1488 patients (mean age, 66.3 years; SD, 11.1; 98% ischemic stroke) were followed for a median of 2.68 years (25th-75th percentile: 1.21-4.14 years). After an initial period of improvement through up to 1-year poststroke, decline was seen in global cognition and all domains except executive function after adjusting for age, sex, education, vascular risk factors, and stroke characteristics (-0.053 SD/year [95% CI, -0.073 to -0.033]; P<0.001 for global cognition). Recurrent stroke and older age were associated with faster decline. Decline was significantly faster in patients with stroke compared with controls (difference=-0.078 SD/year [95% CI, -0.11 to -0.045]; P<0.001 for global cognition in a subgroup analysis). CONCLUSIONS: Patients with stroke experience cognitive decline that is faster than that of stroke-free controls from 1 to 3 years after onset. An increased rate of decline is associated with older age and recurrent stroke.

Validation of the Korean-Everyday Cognition (K-ECog).

BACKGROUND: In the early diagnosis of dementia, an important factor is the evaluation of activities of daily living. The Everyday Cognition (ECog) scale was developed to measure functional changes that are the everyday correlates of specific neuropsychological impairments. This study aimed to examine the validity of the Korean version of Everyday Cognition (K-ECog). METHODS: The participants were 268 cognitively normal older adults (NA), 151 amnestic mild cognitive impairment (aMCI), and 77 dementia of the Alzheimer's type (DAT). The Korean-Mini Mental State Examination (K-MMSE), Korean-Montreal Cognitive Assessment (K-MoCA), and Short form of the Geriatric Depression Scale (SGDS) were administered to all the participants. The K-ECog and Korean-Instrumental Activities of Daily Living (K-IADL) were rated by their informants. RESULTS: Internal consistency (Cronbach's α) of K-ECog global function was 0.93, and its test-retest reliability (Pearson's r) was 0.73. K-ECog was significantly correlated with K-IADL (0.66), K-MMSE (-0.38), and K-MoCA (-0.26). Confirmatory factor analysis of K-ECog yielded seven factor model that the original ECog proposed. K-ECog global score and six domain scores were significantly different across the NA, aMCI, and DAT groups. Receiver operating characteristic curve analyses showed that K-ECog effectively differentiated aMCI and DAT patients from NA, suggesting that K-ECog is as sensitive for detecting functional impairments as K-IADL. The proposed optimal cut-off score to differentiate aMCI from NA was 1.41. CONCLUSION: K-ECog is proven reliable and valid for clinical use. K-ECog can be used to distinguish very early stages of impaired ADL and cognitive impairment in the community.

Dizziness Handicap and Its Contributing Factors in Patients With Migraine.

OBJECTIVE: Dizziness is frequently reported in patients with migraine. However, its assessment is often neglected in clinical practice. We investigated the dizziness handicap experienced by patients with migraine and its contributing factors. METHODS: A total of 361 migraine outpatients (270 women, 91 men; mean age 39.01 ± 11.2 years) were given the Korean Dizziness Handicap Inventory (KDHI) questionnaire (total score: 100 points; cutoff: 29). The Headache Impact Test, Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, and Pittsburgh Sleep Quality Index were also administered. Clinical data such as age, sex, number of headache attacks per month, pain intensity on the visual analog scale, and average sleep hours were collected to find contributing factors. Comparisons were made between chronic and episodic migraine. RESULTS: A total of 153 patients were classified as having dizziness handicap (M+DH) and 208 had migraine without dizziness handicap (M-DH). Patients with M+DH experienced more headache attacks per month than patients with M-DH (P = 0.010). The proportion of patients with chronic migraine was larger in the M+DH group (29.4% vs. 17.3%, P = 0.006). Patients with M+DH showed higher scores than patients with M-DH in all the KDHI subscales. Multivariable logistic regression showed headache impact, pain intensity, anxiety, and depression to be significantly associated with dizziness handicap. CONCLUSION: The data suggest that patients with migraine, especially those with chronic-type migraine, experience physical, emotional, and functional handicaps due to dizziness. Dizziness handicap is related to headache impact, anxiety, and depression. Targeted management of such factors is required to reduce the severity of subjective discomfort.

A Methodological Perspective on the Longitudinal Cognitive Change after Stroke.

BACKGROUND/AIMS: Most studies of poststroke cognitive impairment (PSCI) have analyzed cognitive levels at specific time points rather than their changes over time. Furthermore, they seldom consider correlations between cognitive domains. We aimed to investigate the effects of these methodological considerations on determining significant PSCI predictors in a longitudinal stroke cohort. METHODS: In patients who underwent neuropsychological tests at least twice after stroke, we adopted a multilevel hierarchical mixed-effects model with domain-specific cognitive changes and a multivariate model for multiple outcomes to reflect their correlations. RESULTS: We enrolled 375 patients (median follow-up of 34.1 months). Known predictors of PSCI were generally associated with cognitive levels; however, most of the statistical significances disappeared when cognitive changes were set as outcomes, except age for memory, prior stroke and baseline cognition for executive/attention domain, and baseline cognition for visuospatial function. The multivariate analysis which considered multiple outcomes simultaneously further altered these associations. CONCLUSIONS: This study shows that defining outcomes as changes over time and reflecting correlations between outcomes may affect the identification of predictors of PSCI.

Prediction of post-stroke dementia using NINDS-CSN 5-minute neuropsychology protocol in acute stroke.

BACKGROUND: The National Institute of Neurological Disease and Stroke-Canadian Stroke Network (NINDS-CSN) 5-minute neuropsychology protocol consists of only verbal tasks, and is proposed as a brief screening method for vascular cognitive impairment. We evaluated its feasibility within two weeks after stroke and ability to predict the development of post-stroke dementia (PSD) at 3 months after stroke. METHOD: We prospectively enrolled subjects with ischemic stroke within seven days of symptom onset who were consecutively admitted to 12 university hospitals. Neuropsychological assessments using the NINDS-CSN 5-minute and 60-minute neuropsychology protocols were administered within two weeks and at 3 months after stroke onset, respectively. PSD was diagnosed with reference to the American Heart Association/American Stroke Association statement, requiring deficits in at least two cognitive domains. RESULTS: Of 620 patients, 512 (82.6%) were feasible for the NINDS-CSN 5-minute protocol within two weeks after stroke. The incidence of PSD was 16.2% in 308 subjects who had completed follow-up at 3 months after stroke onset. The total score of the NINDS-CSN 5-minute protocol differed significantly between those with and without PSD (4.0 ± 2.7, 7.4 ± 2.7, respectively; p < 0.01). A cut-off value of 6/7 showed reasonable discriminative power (sensitivity 0.82, specificity 0.67, AUC 0.74). The NINDS-CSN 5-minute protocol score was a significant predictor for PSD (adjusted odds ratio 6.32, 95% CI 2.65-15.05). DISCUSSION: The NINDS-CSN 5-minute protocol is feasible to evaluate cognitive functions in patients with acute ischemic stroke. It might be a useful screening method for early identification of high-risk groups for PSD.

Subjective cognitive decline in patients with migraine and its relationship with depression, anxiety, and sleep quality.

BACKGROUND: Cognitive decline is a major concern in patients with migraine. Depression, anxiety, and/or poor sleep quality are well-known comorbidities of migraine, but available evidence on the subjective cognitive decline (SCD) is limited. This study aimed to investigate the presence and frequency of SCD and its relationship with anxiety, depression and sleep quality in patients with migraine. METHODS: We enrolled patients with migraine who scored within the normal range of the Korean-Mini Mental State Examination and the Korean-Montreal Cognitive Assessment. Using the Subjective Cognitive Decline Questionnaire (SCD-Q), participants with ≥7 were assigned to the SCD group. The Headache Impact Test-6, Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, and Pittsburgh Sleep Quality Index were used and analyzed between the two groups. RESULTS: A total of 188 patients with migraine, aged 38.1 ± 9.9 years, were enrolled. The mean SCD-Q score was 6.5 ± 5.5, and 44.7% of participants were identified as SCD. Migraineurs with SCD reported higher headache pain intensity and headache impact, as well as greater prevalence of anxiety, depression, reduced quality of sleep, and shorter sleep duration during weekdays compared to migraineurs without SCD. There were no significant differences in terms of age, sex, migraine type (chronic/episodic), medication, or sleep duration during weekends between the two groups. Upon multivariate logistic analysis adjusted for age, sex, headache characteristics, and psychological variables, depression was associated with increased risk of SCD (Odds ratio 1.31, 95% confidence interval 1.16-1.49) and sleep duration during weekdays was associated with decreased risk of SCD (Odds ratio 0.66, 95% confidence interval 0.44-0.97). CONCLUSIONS: A non-negligible number of patients with migraine complained of SCD. Depression and short sleep duration during weekdays were related to SCD among adult migraineurs.

Trail Making Test Elucidates Neural Substrates of Specific Poststroke Executive Dysfunctions.

BACKGROUND AND PURPOSE: Poststroke cognitive impairment is typified by prominent deficits in processing speed and executive function. However, the underlying neuroanatomical substrates of executive deficits are not well understood, and further elucidation is needed. There may be utility in fractionating executive functions to delineate neural substrates. METHODS: One test amenable to fine delineation is the Trail Making Test (TMT), which emphasizes processing speed (TMT-A) and set shifting (TMT-B-A difference, proportion, quotient scores, and TMT-B set-shifting errors). The TMT was administered to 2 overt ischemic stroke cohorts from a multinational study: (1) a chronic stroke cohort (N=61) and (2) an acute-subacute stroke cohort (N=45). Volumetric quantification of ischemic stroke and white matter hyperintensities was done on magnetic resonance imaging, along with ratings of involvement of cholinergic projections, using the previously published cholinergic hyperintensities projections scale. Damage to the superior longitudinal fasciculus, which colocalizes with some cholinergic projections, was also documented. RESULTS: Multiple linear regression analyses were completed. Although larger infarcts (ß=0.37, P<0.0001) were associated with slower processing speed, cholinergic hyperintensities projections scale severity (ß=0.39, P<0.0001) was associated with all metrics of set shifting. Left superior longitudinal fasciculus damage, however, was only associated with the difference score (ß=0.17, P=0.03). These findings were replicated in both cohorts. Patients with ≥2 TMT-B set-shifting errors also had greater cholinergic hyperintensities projections scale severity. CONCLUSIONS: In this multinational stroke cohort study, damage to lateral cholinergic pathways and the superior longitudinal fasciculus emerged as significant neuroanatomical correlates for executive deficits in set shifting.

Cortical hubs and subcortical cholinergic pathways as neural substrates of poststroke dementia.

BACKGROUND AND PURPOSE: A role of neural networks in the development of poststroke dementia has not been clearly established. We hypothesized that stroke-mediated disruption of subcortical cholinergic pathway or large-scale neural networks contributes to poststroke dementia. METHODS: A matched case-control study was conducted in a predetermined cohort with acute ischemic stroke. Cases were defined as newly developed dementia diagnosed >3 months after stroke using the Korean Vascular Cognitive Impairment Harmonization Standards. Each case was matched to 2 controls for age, education, and initial stroke severity. The Cholinergic Pathways HyperIntensities Scale was applied with some modifications to characterize disruption of cholinergic pathways by acute stroke lesions. Involvement of major cortical hub locations of the default mode network, central executive network, and salience network was also investigated. RESULTS: After matching, 38 cases and 66 matched controls were included. Cholinergic Pathways HyperIntensities Scale scores were significantly higher in cases than in controls (2.2±2.9 versus 0.9±1.4). Acute ischemic lesions affecting the default mode and central executive networks were more frequently observed in cases compared with controls (36.8% versus 7.6% and 26.3% versus 6.1%, respectively). These findings remained significant in the multiple logistic regression models adjusted for various sets of potential confounders. Lesion location analysis revealed that cases were more likely to have acute lesions in the left corona radiata, hippocampal formation, and posterior parietal cortex. CONCLUSIONS: Disruption of cholinergic pathways and major hubs of large-scale neural networks might contribute to newly developed dementia after acute ischemic stroke.

Post-stroke memory impairment among patients with vascular mild cognitive impairment.

BACKGROUND: The American Stroke Association/American Heart Association recommended the criteria for diagnosis of vascular cognitive impairment and memory impairment (MI) is a feature in the classification of vascular mild cognitive impairment (VaMCI). VaMCI patients with MI may differ in terms of infarct location or demographic features, so we evaluated the clinical characteristics associated with MI in patients with VaMCI. METHODS: A prospective multicenter study enrolled 353 acute ischemic stroke patients who underwent evaluation using the Korean Vascular Cognitive Impairment Harmonization Standard Neuropsychological Protocol at three months after onset. The association between MI and demographic features, stroke risk factors, and infarct location was assessed. RESULTS: VaMCI was diagnosed in 141 patients, and 58 (41.1%) exhibited MI. Proportions of men and of left side infarcts were higher in VaMCI with MI than those without (75.9 vs. 57.8%, P = 0.03, 66.7 vs. 47%, P = 0.02). Multiple logistic analyses revealed that male sex (odds ratio [OR] 3.07, 95% confidence interval [95% CI] 1.12-8.42), left-side infarcts (OR 3.14, 95% CI 1.37-7.20), and basal ganglia/internal capsule infarcts (OR 4.53, 95% CI 1.55-13.22) were associated with MI after adjusting other demographic variables, vascular risk factors, and subtypes of stroke. CONCLUSIONS: MI is associated with sex and infarct location in VaMCI patients.

Highly variable blood pressure as a predictor of poor cognitive outcome in patients with acute lacunar infarction.

OBJECTIVE AND BACKGROUND: Many patients develop cognitive impairment after an acute stroke. It is not clear whether blood pressure variability is a prognostic factor for cognitive impairment. We aimed to determine the association between blood pressure variability on hospital admission and cognitive outcome in patients with acute lacunar infarction. METHODS: We performed a retrospective analysis on 22 men and 14 women (mean age, 61.8 years) who had completed a cognitive evaluation 3 months after onset of an acute lacunar infarction. The patients had no previous functional disability or dementia, stenosis in major cerebral arteries, cardiac embolic sources, or infarct in strategic territories for cognition. We used standard deviation and coefficient of variance as parameters of blood pressure variability, and each cognitive function test z score as an outcome parameter. We performed linear regression analysis to assess the relationship between blood pressure variability and cognition, adjusted for vascular risk factors, severity of neurologic deficits, and mean blood pressure. RESULTS: High variability of both systolic and diastolic blood pressure was significantly associated with low z scores on the Controlled Oral Word Association Test and the Digit Symbol Coding test (P<0.01). High variability of diastolic blood pressure was significantly associated with low z scores on the Korean Mini-Mental State Examination and Seoul Verbal Learning Test delayed recall (P<0.01). CONCLUSIONS: Highly variable blood pressure on admission for acute lacunar infarction may predict poor cognitive outcomes, especially frontal lobe dysfunction.

Cognitive impairment evaluated with Vascular Cognitive Impairment Harmonization Standards in a multicenter prospective stroke cohort in Korea.

BACKGROUND AND PURPOSE: Since the Vascular Cognitive Impairment Harmonization Standards (VCIHS) neuropsychological test protocol was proposed by the National Institute of Neurological Disorders and Stroke and Canadian Stroke Network, no studies have applied this neuropsychological protocol to poststroke survivors in a large-scale, multicenter stroke cohort. We determined the frequency of vascular cognitive impairment (VCI) and investigated the feasibility of using the Korean version of the VCIHS neuropsychological protocol in a multicenter, hospital-based stroke cohort in Korea. METHODS: We prospectively enrolled 620 subjects with ischemic stroke within 7 days of symptom onset among 899 patients who were consecutively admitted to 12 university hospitals in Korea. Neuropsychological assessments using the 60-minute Korean VCIHS neuropsychological protocol were administered at 3 months after stroke. RESULTS: Of the 620 patients, 506 were followed up at 3 months after stroke. Of these, 353 (69.8%) were evaluated for cognitive function using the 60-minute Korean VCIHS neuropsychological protocol. The frequency of VCI at 3 months was 62.6%: VCI with no dementia in 49.9% and vascular dementia in 12.7%. Old age (P=0.014), poor functional outcomes at 3 months (P=0.029), and stroke subtypes other than small vessel disease (P=0.004) were independent risk factors of VCI. CONCLUSIONS: VCI, evaluated using the Korean VCIHS neuropsychological protocol, is substantial at 3 months after ischemic stroke in Korea. The use of the 60-minute Korean VCIHS neuropsychological protocol was feasible in large-scale multicenter studies.

Effect of Education on Discriminability of Montreal Cognitive Assessment Compared to Mini-Mental State Examination.

Background and Purpose: The Montreal Cognitive Assessment (MoCA) has been known as a screening test for detecting mild cognitive impairment (MCI) better than Mini-Mental State Examination (MMSE). However, in previous domestic studies, no significant difference was found in the discriminability between MoCA and MMSE. Researchers have suggested that this might be because older Koreans are less educated than older Westerners. This study was conducted to examine the effect of education on the discriminability of MoCA compared to the MMSE. Methods: Participants were 123 cognitively normal elderly, 118 with vascular MCI, 108 with amnestic MCI, 121 with vascular dementia, and 113 with dementia of the Alzheimer's type. The Korean-MoCA (K-MoCA) and Korean-MMSE (K-MMSE) were administered. Multiple regression analyses and receiver operating characteristic (ROC) curve analyses were performed. Results: In all participants, education significantly affected both K-MoCA and K-MMSE scores along with age. The effect of education was re-examined by subgroup analysis after dividing subjects according to the level of education. Effect of education on K-MoCA and K-MMSE was only shown in the group with <9 years of education. ROC curve analyses revealed that the discriminability of K-MoCA to differentiate between vascular MCI and normal elderly was significantly higher than that of K-MMSE. When re-examining subgroups divided by education level, however, this higher discriminability of K-MoCA disappeared in the group with <9 years of education. Conclusions: These results indicate no difference in discriminating cognitive deficits between K-MoCA and K-MMSE in Korean elderly with <9 years of education.

Strategic Infarct Locations for Poststroke Depressive Symptoms: A Lesion- and Disconnection-Symptom Mapping Study.

BACKGROUND: Depression is the most common neuropsychiatric complication after stroke. Infarct location is associated with poststroke depressive symptoms (PSDS), but it remains debated which brain structures are critically involved. We performed a large-scale lesion-symptom mapping study to identify infarct locations and white matter disconnections associated with PSDS. METHODS: We included 553 patients (mean [SD] age = 69 [11] years, 42% female) with acute ischemic stroke. PSDS were measured using the 30-item Geriatric Depression Scale. Multivariable support vector regression (SVR)-based analyses were performed both at the level of individual voxels (voxel-based lesion-symptom mapping) and at predefined regions of interest to relate infarct location to PSDS. We externally validated our findings in an independent stroke cohort (N = 459). Finally, disconnectome-based analyses were performed using SVR voxel-based lesion-symptom mapping, in which white matter fibers disconnected by the infarct were analyzed instead of the infarct itself. RESULTS: Infarcts in the right amygdala, right hippocampus, and right pallidum were consistently associated with PSDS (permutation-based p < .05) in SVR voxel-based lesion-symptom mapping and SVR region-of-interest analyses. External validation confirmed the association between infarcts in the right amygdala and pallidum, but not the right hippocampus, and PSDS. Disconnectome-based analyses revealed that disconnections in the right parahippocampal white matter, right thalamus and pallidum, and right anterior thalamic radiation were significantly associated (permutation-based p < .05) with PSDS. CONCLUSIONS: Infarcts in the right amygdala and pallidum and disconnections of right limbic and frontal cortico-basal ganglia-thalamic circuits are associated with PSDS. Our findings provide a comprehensive and integrative picture of strategic infarct locations for PSDS and shed new light on pathophysiological mechanisms of depression after stroke.

Efficacy and safety of oxiracetam in patients with vascular cognitive impairment: A multicenter, randomized, double-blinded, placebo-controlled, phase IV clinical trial.

BACKGROUND: Oxiracetam may have a modest effect on preventing cognitive decline. Exercise can also enhance cognitive function. This trial aims to investigate the effect of oxiracetam on post-stroke cognitive impairment and explore whether this effect is modified by exercise. Furthermore, the mechanisms that mediate this effect will be investigated through a neural network analysis. METHODS: This is a multicenter, randomized, double-blind, placebo-controlled phase IV trial. Patients who complained of cognitive decline 3 months after stroke and had a high risk of cognitive decline were eligible. Patients were randomly assigned to receive either 800 mg of oxiracetam or placebo twice daily for 36 weeks. After randomization, a predetermined exercise protocol was provided to each participant, and the degree of physical activity was assessed using wrist actigraphy at 4, 12, 24, and 36 weeks. Resting-state functional MRI was obtained in baseline and 36-week follow-up. Co-primary endpoints are changes in the Mini-Mental State Examination and Clinical Dementia Rating-Sum of Boxes. Secondary endpoints include changes in the NINDS-CSN VCIHS-Neuropsychology Protocol, Euro QoL, patient's global assessment, and functional network connectivity. If there is a significant difference in physical activity between the two groups, the interaction effect between physical activity and the treatment group will be examined. A total of 500 patients were enrolled from February 2018, and the last patient's final follow-up was completed in September 2022. CONCLUSION: This trial is meaningful not only to prove the efficacy of oxiracetam, but also evaluate whether exercise can modify the effects of medication and how cognitive function can be restored. Trial registrationhttp://cris.nih.go.kr (KCT0005137).

Network impact score is an independent predictor of post-stroke cognitive impairment: A multicenter cohort study in 2341 patients with acute ischemic stroke.

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/.

Measurement of Subjective Cognitive Decline (SCD) Using Korean-Everyday Cognition (K-ECog) as a Screening Tool: a Feasibility Study.

BACKGROUND AND PURPOSE: Everyday Cognition (ECog) has been widely used to differentiate individuals with mild cognitive impairment (MCI) and dementia from normal elderly individuals. It has also been used to assess subjective cognitive decline (SCD). This study investigated the feasibility of using ECog as a screening measure for SCD in community-dwelling elderly individuals. METHODS: The participants included 84 older adults with and 93 without SCD living in the community. These 2 groups were classified based on their response ("yes" or "no") to the question "Do you perceive memory or cognitive difficulties?" All participants were evaluated using the Korean-Mini Mental State Examination (K-MMSE), Short form of the Geriatric Depression Scale (SGDS), and the Korean version of Everyday Cognition (K-ECog). RESULTS: The scores of all participants were within the normal range on the K-MMSE and SGDS. The total K-MMSE score did not differ significantly between the 2 groups after controlling for age, education, and depression. The scores of SCD group were significantly higher than those of the non-SCD group for memory, language, and executive function: planning domains, as well as K-ECog total score. Receiver operating characteristic curve analysis revealed that the K-ECog total score was effective in moderately differentiating between subjects with and without SCD (area under the curve: 0.73). CONCLUSIONS: ECog is a feasible and useful screening measure for SCD in older adults living in the community, and can be used to assess the full spectrum of cognitive and functional deficits, ranging from SCD to MCI and dementia.

Validity of the Montreal Cognitive Assessment (MoCA) Index Scores: a Comparison with the Cognitive Domain Scores of the Seoul Neuropsychological Screening Battery (SNSB).

BACKGROUND AND PURPOSE: A new approach was proposed to score the Montreal Cognitive Assessment (MoCA) index scores for 6 cognitive domains: orientation (OIS), attention (AIS), language (LIS), visuospatial function (VIS), memory (MIS), and executive function (EIS). This study investigated whether the MoCA index scores represent the functions of each cognitive domain by examining the correlations with the corresponding cognitive domain scores derived from conventional neuropsychological tests included in the Seoul Neuropsychological Screening Battery, 2nd Edition (SNSB-II). METHODS: The participants were 104 amnestic mild cognitive impairment (aMCI), 74 vascular mild cognitive impairment (VaMCI), 73 dementia of the Alzheimer's type (DAT), and 41 vascular dementia (VaD) patients. All participants were administered the Korean-MoCA and SNSB-II. RESULTS: Like the MoCA total score, the MoCA-OIS, MoCA-VIS, and MoCA-MIS showed differences between aMCI and AD groups and between VaMCI and VaD groups. The MoCA-AIS, MoCA-LIS, and MoCA-EIS showed significant differences between VaMCI and VaD groups, but no difference between aMCI and DAT groups. In the aMCI and VaMCI groups, all index scores of the MoCA showed significant correlations with the corresponding cognitive domain scores of the SNSB-II. Except for MoCA-MIS, the MoCA-AIS, MoCA-LIS, MoCA-VIS, and MoCA-EIS also showed significant correlations with the corresponding domain scores of the SNSB-II in the DAT and VaD groups. CONCLUSIONS: These results indicate that all MoCA index scores, except for MoCA-MIS, which does not reflect the severity of memory impairment in dementia patients, provide highly valid information on the function of each cognitive domain in patients with mild cognitive impairment and dementia.

A Comparison of the Performance between the 60- and 120-Second Conditions of the Korean-Color Word Stroop Test: Color Reading (K-CWST: CR).

BACKGROUND AND PURPOSE: The Korean-Color Word Stroop Test: Color Reading (K-CWST: CR) included in the Seoul Neuropsychological Screening Battery, 2nd Edition (SNSB-II) examines inhibitory control deficit. It provides normative data for both 60- and 120-second conditions, but the validity of the 60-second condition has not yet been proven. This study examined the validity of the 60-second condition by observing concordance between the performances in cognitively normal, MCI, and mild dementia groups. METHODS: There were 1,336 patients performed the SNSB-II, including the K-CWST: CR. Based on the cognitive test results, activities of daily living, and clinical interview, the patients were assigned to normal cognition (n=104), MCI (n=884), or mild dementia (n=348) groups. Abnormal performance on the K-CWST: CR was operationally defined as 1SD below the normative mean. The receiver operating characteristic curve analyses were conducted to compare the discriminability between the 60- and 120-second conditions. RESULTS: The percentages of abnormal performance in the MCI group were 41.5% and 42.3%, and those in the mild dementia group were 82.7% and 82.4% for the 60- and 120-second conditions, respectively. The areas under the curve for the 60- and 120-seconds were as follows; 0.80 and 0.81 in differentiating normal from MCI; 0.95 and 0.96 in normal from mild dementia; and 0.77 and 0.77 in MCI from mild dementia. CONCLUSIONS: The 60-second condition of the K-CWST showed very similar results, not statistically different from the 120-second condition. Therefore, the 60-second condition could be used interchangeably with the 120-second condition in a clinical setting.