Dataset Information

Investigation of reactive astrogliosis effect on post-stroke cognitive impairment.

ABSTRACT:

Background

The aim of this study is to investigate the associations between post-stroke cognitive impairment (PSCI) severity and reactive astrogliosis (RA) extent on normalized ¹⁸F-THK-5351 positron-emission tomography (PET) imaging in amyloid-negative patients with first-ever stroke.

Methods

We prospectively enrolled 63 amyloid-negative patients with first-ever stroke. Neurocognitive evaluation, MRI, ¹⁸F-THK-5351, and ¹⁸F-florbetapir PET were performed around 3 months after stroke. The ¹⁸F-THK-5351 uptake intensity was normalized using a signal distribution template to obtain the Z-SUM scores as the RA extent in the whole brain and cerebral hemisphere ipsilateral to stroke lesion. We evaluated stroke volume, leukoaraiosis, and brain atrophy on MRI. We used a comprehensive neurocognitive battery to obtain composite cognitive scores, and defined PSCI as a general cognitive function score < -?1. We analyzed the influence of Z-SUM scores on PSCI severity after adjusting for demographic, vascular, and neurodegenerative variables.

Results

Twenty-five of 63 stroke patients had PSCI. Patients with PSCI had older age, lower education, and more severe cortical atrophy and total Z-SUM scores. Total Z-SUM scores were significantly associated with general cognitive and executive functions at multiple regression models. Path analyses showed that stroke can exert cognitive influence directly by stroke itself as well as indirectly through RA, including total and ipsilateral Z-SUM scores, in patients with either right or left hemisphere stroke.

Conclusion

The patterns and intensity of ¹⁸F-THK-5351 uptake in amyloid-negative patients with first-ever stroke were associated with PSCI manifestations, which suggests that RA presents a modulating effect in PSCI development.

SUBMITTER: Huang KL

PROVIDER: S-EPMC7568828 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Publications

Investigation of reactive astrogliosis effect on post-stroke cognitive impairment.

Huang Kuo-Lun KL Hsiao Ing-Tsung IT Ho Meng-Yang MY Hsu Jung-Lung JL Chang Yeu-Jhy YJ Chang Ting-Yu TY Liu Chi-Hung CH Chang Chien-Hung CH Wu Yi-Ming YM Wu Kuan-Yi KY Wey Shiaw-Pyng SP Yen Tzu-Chen TC Okamura Nobuyuki N Lee Tsong-Hai TH Lin Kun-Ju KJ

Journal of neuroinflammation 20201017 1

<h4>Background</h4>The aim of this study is to investigate the associations between post-stroke cognitive impairment (PSCI) severity and reactive astrogliosis (RA) extent on normalized <sup>18</sup>F-THK-5351 positron-emission tomography (PET) imaging in amyloid-negative patients with first-ever stroke.<h4>Methods</h4>We prospectively enrolled 63 amyloid-negative patients with first-ever stroke. Neurocognitive evaluation, MRI, <sup>18</sup>F-THK-5351, and <sup>18</sup>F-florbetapir PET were perf ...[more]

PMID: 33069238

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Project description:ImportanceSecondary prevention interventions to reduce post-stroke cognitive impairment (PSCI) can be aided by the early identification of high-risk individuals who would benefit from risk factor modification.ObjectiveTo develop and evaluate a predictive model to identify patients at increased risk of PSCI over 5 years using data easily accessible from electronic health records.DesignCohort study with patients enrolled between 2003-2016 with follow-up through 2022.SettingPrimary care practices affiliated with two academic medical centers.ParticipantsIndividuals 45 years or older, without prior stroke or prevalent cognitive impairment, with primary care visits and an incident ischemic stroke between 2003-2016 (development/internal validation cohort) or 2010-2022 (external validation cohort).ExposuresPredictors of PSCI were ascertained from the electronic health record.Main outcomeThe outcome was incident dementia/cognitive impairment within 5 years and beginning 3 months following stroke, ascertained using ICD-9/10 codes. For model variable selection, we considered potential predictors of PSCI and constructed 400 bootstrap samples with two-thirds of the model derivation sample. We ran 10-fold cross-validated Cox proportional hazards models using a least absolute shrinkage and selection operator (LASSO) penalty. Variables selected in >25% of samples were included.ResultsThe analysis included 332 incident diagnoses of PSCI in the development cohort (n=3,741), and 161 and 128 incident diagnoses in the internal (n=1,925) and external (n=2,237) validation cohorts. The c-statistic for predicting PSCI was 0.731 (95% CI: 0.694-0.768) in the internal validation cohort, and 0.724 (95% CI: 0.681-0.766) in the external validation cohort. A risk score based on the beta coefficients of predictors from the development cohort stratified patients into low (0-7 points), intermediate (8-11 points), and high (12-35 points) risk groups. The hazard ratios for incident PSCI were significantly different by risk categories in internal (High, HR: 6.2, 95% CI 4.1-9.3; Intermediate, HR 2.7, 95% CI: 1.8-4.1) and external (High, HR: 6.1, 95% CI: 3.9-9.6; Intermediate, HR 2.8, 95% CI: 1.9-4.3) validation cohorts.Conclusions and relevanceFive-year risk of PSCI can be accurately predicted using routinely collected data. Model output can be used to risk stratify and identify individuals at increased risk for PSCI for preventive efforts.

Project description:ObjectivePost-stroke cognitive impairment (PSCI) is resistant to treatment. Recent studies have widely applied repetitive transcranial magnetic stimulation (rTMS) to treat various brain dysfunctions, such as post-stroke syndromes. Nonetheless, a protocol for PSCI has not been established. Therefore, this study is aimed to evaluate the therapeutic effect of our high-frequency rTMS protocol for PSCI during the chronic phase of stroke.MethodsIn this prospective study, ten patients with PSCI were enrolled and received high-frequency rTMS on the ipsilesional dorsolateral prefrontal cortex (DLPFC) for 10 sessions (5 days per week for 2 weeks). Cognitive and affective abilities were assessed at baseline and 2 and 14 weeks after rTMS initiation. To investigate the therapeutic mechanism of rTMS, the mRNA levels of pro-inflammatory cytokines (interleukin (IL)-6, IL-1β, transforming growth factor beta [TGF-β], and tumor necrosis factor alpha [TNF-α]) in peripheral blood samples were quantified using reverse transcription polymerase chain reaction, and cognitive functional magnetic resonance imaging (fMRI) was conducted at baseline and 14 weeks in two randomly selected patients after rTMS treatment.ResultsThe scores of several cognitive evaluations, i.e., the Intelligence Quotient (IQ) of Wechsler Adult Intelligence Scale, auditory verbal learning test (AVLT), and complex figure copy test (CFT), were increased after completion of the rTMS session. After 3 months, these improvements were sustained, and scores on the Mini-Mental Status Examination and Montreal Cognitive Assessment (MoCA) were also increased (p < 0.05). While the Geriatric Depression Scale (GeDS) did not show change among all patients, those with moderate-to-severe depression showed amelioration of the score, with marginal significance. Expression of pro-inflammatory cytokines was decreased immediately after the ten treatment sessions, among which, IL-1β remained at a lower level after 3 months. Furthermore, strong correlations between the decrease in IL-6 and increments in AVLT (r = 0.928) and CFT (r = 0.886) were found immediately after the rTMS treatment (p < 0.05). Follow-up fMRI revealed significant activation in several brain regions, such as the medial frontal lobe, hippocampus, and angular area.ConclusionsHigh-frequency rTMS on the ipsilesional DLPFC may exert immediate efficacy on cognition with the anti-inflammatory response and changes in brain network in PSCI, lasting at least 3 months.

Project description:Background: Non-linguistic cognitive training has been suggested to improve the communication skills of patients with post-stroke aphasia (PSA). However, the association between language and non-linguistic cognitive functions is not fully understood. In this study, we used the Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) to evaluate the characteristics of non-linguistic cognitive impairments in Chinese PSA patients. Methods: A total of 86 stroke patients were recruited in this study. Language and non-linguistic cognitive impairments were evaluated by the Western Aphasia Battery (WAB) and LOTCA, respectively. The patients were divided into two groups (PSA and non-PSA), and the Chinese norm (the data came from 44 Chinese individuals without neurological disorders in a previous study) was used as the control group. The LOTCA scores were compared among the three groups. Patients in the PSA group were subdivided into the fluent aphasia group (FAG) and the non-FAG according to the Chinese aphasia fluency characteristic scale. The LOTCA scores were also compared between the PSA subdivisions. Potential confounders were adjusted in the analysis of covariance. Partial correlation analysis between the subscores of WAB and LOTCA was also performed. Results: The total LOTCA scores in the PSA group (75.11 ± 17.08) were significantly lower compared with scores in the non-PSA (96.80 ± 7.75, P < 0.001) and the control group (97.65 ± 16.24, P < 0.001). The PSA group also had lower orientation, visual perception (VP), spatial perception (SP), visuomotor organization, thinking operation, and attention scores. The total LOTCA, orientation, VP, SP, and MP scores were lower in the non-FAG (69.24 ± 18.06, 8.62 ± 5.09, 12.76 ± 2.47, 7.48 ± 3.01, and 9.62 ± 2.25, respectively) compared with the FAG (80.36 ± 14.07, 12.14 ± 3.99, 14.09 ± 1.93, 9.68 ± 3.01, 10.55 ± 1.63, respectively, P's < 0.05). The aphasia quotient was positively correlated with the total score of LOTCA and scores of orientation, VP, SP, and MP (r = 0.710, 0.744, 0.565, 0.597, and 0.616; P < 0.001). Conclusion: Compared with stroke patients without aphasia, patients with PSA often have more extensive and serious non-linguistic cognitive impairments. Patients with non-fluent aphasia often present with serious cognitive impairments than those with fluent aphasia, especially the impairments of orientation and SP. Non-linguistic cognitive impairments correlate with language impairments in aphasia.

Project description:Background and Aims: Systemic inflammation is associated with an increased risk of cognitive impairment and dementia, but the associations between them in stroke patients are less clear. We examined the impact of systemic inflammation represented as the neutrophil-lymphocyte ratio (NLR) on the development of post-stroke cognitive impairment (PSCI) and domain-specific cognitive outcomes 3-month after ischemic stroke. Methods: Using prospective stroke registry data, we consecutively enrolled 345 participants with ischemic stroke whose cognitive functions were evaluated 3-month after stroke. Their cognition was assessed with the Korean version of the Vascular Cognitive Impairment Harmonization Standards and the Korean-Mini Mental Status Examination. PSCI was defined as a z-score of < -2 standard deviations for age, sex, and education adjusted means in at least one cognitive domain. The participants were categorized into five groups according to the quintiles of NLR (lowest NLR, Q1). The cross-sectional association between NLR and PSCI was assessed using multiple logistic regression, adjusting for age, sex, education, vascular risk factors, and stroke type. Results: A total of 345 patients were enrolled. The mean age was 63.0 years and the median NIHSS score and NLR were 2 [1-4] and 2.26 [1.65-2.91], respectively. PSCI was identified in 71 (20.6%) patients. NLR was a significant predictor for PSCI both as a continuous variable (adjusted OR, 1.14; 95% CI, 1.00-1.31) and as a categorical variable (Q5, adjusted OR, 3.26; 95% CI, 1.17-9.08). Patients in the Q5 group (NLR ≥ 3.80) showed significantly worse performance in global cognition and in visuospatial and memory domains. Conclusions: NLR in the acute stage of ischemic stroke was independently associated with PSCI at 3 months after stroke, and high NLR was specifically associated with cognitive dysfunction in the memory and visuospatial domains. Thus, systemic inflammation may be a modifiable risk factor that may influence cognitive outcomes after stroke.

Project description: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.

Dataset Information

Investigation of reactive astrogliosis effect on post-stroke cognitive impairment.

Background

Methods

Results

Conclusion

Publications

Investigation of reactive astrogliosis effect on post-stroke cognitive impairment.

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