Stress-Induced Hyperglycemia and Remote Diffusion-Weighted Imaging Lesions in Primary Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Stress-induced hyperglycemia (SIH) is the relative transient increase in glucose during a critical illness such as intracerebral hemorrhage (ICH) and is likely to play an important role in the pathogenesis of remote diffusion-weighted imaging (DWI) lesion (R-DWIL) in primary ICH. We sought to determine the association between SIH and the occurrence of R-DWILs. METHODS: We prospectively enrolled primary ICH patients within 14 days after onset from November 2016 to May 2018. In these patients, cerebral magnetic resonance imaging was performed within 14 days after ICH onset. R-DWIL was defined as a hyperintensity signal in DWI with corresponding hypointensity in apparent diffusion coefficient, and at least 20 mm apart from the hematoma. SIH was measured by stress-induced hyperglycemia ratio (SHR). SHR was calculated by fasting blood glucose (FBG) divided by estimated average glucose derived from glycosylated hemoglobin. The included patients were dichotomized into two groups by the 50th percentile of SHR, and named as SHR (-P50) group and SHR (P50+) group, respectively. We evaluated the association between SHR and R-DWIL occurrence using multivariable logistic regression modeling adjusted for potential confounders. RESULTS: Among the 288 patients enrolled, forty-six (16.0%) of them had one or more R-DWILs. Compared with the patients in the lower 50% of SHR (SHR [-P50]), the odds ratio (OR) [95% confidence interval (CI)] for the higher 50% of SHR (SHR [P50+]) group for R-DWIL occurrence was 3.13 (1.39-7.07) in the total population and 6.33 (2.19-18.30) in population absent of background hyperglycemia after adjusting for potential covariates. Similar results were observed after further adjusted for FBG. CONCLUSIONS: Our study demonstrated that SIH was associated with the occurrence of R-DWILs in patients with primary ICH within 14 days of symptom onset.

Plasma metabolite profiles of Alzheimer's disease and mild cognitive impairment.

Previous studies have demonstrated altered metabolites in samples of Alzheimer's disease (AD) patients. However, the sample size from many of them is relatively small and the metabolites are relatively limited. Here we applied a comprehensive platform using ultraperformance liquid chromatography-time-of-flight mass spectrometry and gas chromatography-time-of-flight mass spectrometry to analyze plasma samples from AD patients, amnestic mild cognitive impairment (aMCI) patients, and normal controls. A biomarker panel consisting of six plasma metabolites (arachidonic acid, N,N-dimethylglycine, thymine, glutamine, glutamic acid, and cytidine) was identified to discriminate AD patients from normal control. Another panel of five plasma metabolites (thymine, arachidonic acid, 2-aminoadipic acid, N,N-dimethylglycine, and 5,8-tetradecadienoic acid) was able to differentiate aMCI patients from control subjects. Both biomarker panels had good agreements with clinical diagnosis. The 2 panels of metabolite markers were all involved in fatty acid metabolism, one-carbon metabolism, amino acid metabolism, and nucleic acid metabolism. Additionally, no altered metabolites were found among the patients at different stages, as well as among those on anticholinesterase medication and those without anticholinesterase medication. These findings provide a comprehensive global plasma metabolite profiling and may contribute to making early diagnosis as well as understanding the pathogenic mechanism of AD and aMCI.

Early elevated neutrophil-to-lymphocyte ratio associated with remote diffusion-weighted imaging lesions in acute intracerebral hemorrhage.

AIMS: To explore the relationship between the circulating neutrophil-to-lymphocyte ratio (NLR) and the remote diffusion-weighted imaging lesions (R-DWILs) after spontaneous intracerebral hemorrhage (ICH). METHODS: Consecutive patients with spontaneous ICH were prospectively collected from November 2016 to May 2018 and retrospectively analyzed. We included subjects who presented within 24 hours after symptom onset and were free of detectable infections on admission or in hospital. Blood samples were obtained at 24-48 hours after ICH ictus, while all complete MRI scans were performed at 5-8 days. R-DWILs were defined as focal hyperintensities remote from the site of the ICH or the peri-hematoma regions. NLR was calculated by dividing the absolute neutrophil counts by the absolute lymphocyte counts. Multivariate binary logistic regression models were generated to evaluate the relationship between NLR and R-DWILs. RESULTS: One hundred sixty-three subjects met eligibility criteria (age 62.3 ± 13.6 years, 60.7% males), of whom 31(19.0%) experienced R-DWILs. Higher circulating NLR was documented in patients with R-DWILs. With the best cutoff value of 6.01, elevated NLR was independently associated with the presence of R-DWILs (OR = 3.170, 95% CI 1.306-7.697, P = .011) in the bivariate logistic regression analysis with adjustment for age, sex, atrial fibrillation, previous ischemic stroke/TIA, SBP on admission, hematoma volume, and IVH. CONCLUSIONS: This study provides significant evidence of the association between circulating NLR and R-DWILs in spontaneous ICH patients. Patients with NLR > 6.01 at 24-48 hours after ICH ictus should be paid more attention to when evaluating R-DWILs.

Association of Renal Dysfunction With Remote Diffusion-Weighted Imaging Lesions and Total Burden of Cerebral Small Vessel Disease in Patients With Primary Intracerebral Hemorrhage.

Objective: Remote diffusion-weighted imaging (DWI) lesions (R-DWIL) found in intracerebral hemorrhage (ICH) patients are considered as an additional marker of cerebral small vessel disease (cSVD). This study aimed to investigate the association of renal dysfunction and R-DWIL, as well as the total burden of cSVD on magnetic resonance imaging among patients with primary ICH. Methods: One hundred and twenty-six consecutive patients were prospectively enrolled. R-DWIL on DWI, as well as other imaging markers of cSVD, including lacunes, white matter lesions, cerebral microbleeds, and enlarged perivascular spaces were rated using validated scales. Renal dysfunction was evaluated either by reduced estimated glomerular filtration rate (eGFR) or the presence of proteinuria or increased cystatin C. Results: After adjustments for potential confounders by logistic regression, impaired eGFR [odds ratio (OR) 6.00, 95% confidence interval (CI) 1.73-20.78], proteinuria (OR 3.07, 95% CI 1.25-7.54) and increased cystatin C (OR 2.73, 95% CI 1.11-6.72) were correlated with presence of R-DWIL. A similar association was also found between cystatin C levels (OR 3.16, 95% CI 1.39-7.19), proteinuria (OR 2.79, 95% CI 1.34-5.83) and the comprehensive cSVD burden. Conclusions: Renal dysfunction are associated with the presence of R-DWIL, and total burden of cSVD in patients with primary ICH.

Factors Associated With Remote Diffusion-Weighted Imaging Lesions in Spontaneous Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Remote diffusion-weighted imaging lesions (R-DWILs) have been detected in patients with spontaneous intracerebral hemorrhage (ICH) and may be correlated with clinical outcome. However, the mechanisms and characteristics of R-DWILs have not been fully elucidated. In this study, we sought to demonstrate the clinical characteristics of R-DWILs in spontaneous ICH. METHODS: We prospectively collected data with spontaneous ICH patients from November 2016 to December 2017. In these patients, cerebral magnetic resonance imaging was performed within 28 days after ICH onset. R-DWIL was defined as a hyperintensity signal in diffusion-weighted imaging with corresponding hypointensity in apparent diffusion coefficient, and at least 20 mm apart from the hematoma. We compared two groups of patients with or without R-DWIL with the demographic and clinical characteristics, laboratory parameters, and imaging characteristics, by using univariate and multivariate analysis. RESULTS: Of the 222 patients enrolled, a total of 75 R-DWILs were observed in 41 patients (18.5%). Among these lesions, the cortical and subcortical areas were the predominant locations with a proportion of 77.3%. The median diameter of R-DWILs was 7 mm (range 2-20 mm). Twelve patients were found having more than one lesion, with five among which showed R-DWILs in multiple cerebral arterial territories. In multivariate modeling, higher fasting glucose (OR 1.231; 95% CI 1.035-1.465; p = 0.019) and more severe white matter hyperintensity (WMH) (OR 6.589; 95% CI 2.975-14.592; p < 0.001) were independent factors related to the presence of R-DWILs. CONCLUSION: In our study, approximately one-fifth of ICH patients showed coexistence of R-DWIL. Higher fasting glucose and more severe WMH were associated with R-DWIL occurrence in spontaneous ICH.

Remote Diffusion-Weighted Imaging Lesions in Intracerebral Hemorrhage: Characteristics, Mechanisms, Outcomes, and Therapeutic Implications.

Spontaneous intracerebral hemorrhage (ICH) is one of the most fatal form of stroke, with high mortality and disability rate. Small diffusion-weighed imaging lesions are not rare to see in regions remote from the hematoma after ICH and have been generally considered as related with poor outcome. In this review, we described the characteristics of remote ischemic lesions, discussed the possible mechanisms and clinical outcomes of these lesions, and evaluated the potential therapeutic implications.

Risk factors for cognitive decline in elderly people: findings from the two-year follow-up study in a Shanghai urban community.

BACKGROUND: The prevalence of cognitive impairment (CI) and its associated risk factors among elderly peoples in China has been investigated. However, dynamic studies revealing the risk factors associated with cognitive decline from follow-up observations in China are rarely performed. OBJECTIVE: The present study aimed to identify factors predicting late-life cognitive decline in China. METHODS: Participants were 223 community-dwelling residents (≥65 years old) from the urban community of Shanghai with no CI upon comprehensive assessments at baseline. Cognitive decline at 2-year follow-up was defined as a drop of two or more points from baseline score in the Mini-Mental State Examination (MMSE). Associations with baseline demographic, lifestyle, health, and medical factors were then determined within the population. RESULTS: After 2 years, cognitive decline and incident CI developed in 75 (33.6%) and 25 (11.2%) participants, respectively. Across all participants, risk factors for cognitive decline included low education, high body mass index, and diabetes mellitus. Among participants with cognitive decline, points were predominantly lost in items relating to time orientation and complex commands in the MMSE. CONCLUSION: This study confirms the differences in risk factors between cross-sectional and longitudinal studies for cognitive decline among the elderly population in urban Shanghai. Interventions tailored to potential risk factors associated with cognitive decline may offer further benefits.

The impact of human-computer interaction-based comprehensive training on the cognitive functions of cognitive impairment elderly individuals in a nursing home.

BACKGROUND: Given the increasing prevalence of dementia, any intervention that can effectively slow the deterioration of cognitive function is of great importance. OBJECTIVE: This study investigated the efficacy of a human-computer interaction-based comprehensive cognitive training program in cognitively impaired elderly individuals living in a nursing home. METHODS: All subjects, who were aged ≥70 years and had cognitive impairment, were randomly allocated to an intervention group (n = 19) or a control group (n = 14). The intervention group received human-computer interaction-based comprehensive cognitive training for 24 weeks. Neuropsychological examinations were conducted before and after this period. The intervention group was subdivided into two groups according to the scores of global cortical atrophy (GCA) to evaluate the impact of training effectiveness on GCA. RESULTS: After 24 weeks, neither group showed a significant change compared with baseline cognitive examinations. However, there was a tendency for greater improvement in memory, language, and visuospatial abilities for the intervention group as compared with controls. Patients with mild cognitive impairment showed improvements in language and visuospatial capacity, while patients with dementia showed improvements in attention/orientation, memory, language, and fluency. However, none of these findings were statistically significant. The results for the intervention subgroups showed that visuospatial ability improvement was significantly greater among those with a global cortical atrophy score of ≤15 (p < 0.05). CONCLUSION: Human-computer interaction-based comprehensive training may improve cognitive functions among cognitively impaired elderly individuals. The training effect was most prominent among those with milder cerebral atrophy.

Metabolomics: a novel approach to identify potential diagnostic biomarkers and pathogenesis in Alzheimer's disease.

Although the pathogenesis of Alzheimer's disease (AD) is still not fully understood, it is acknowledged that intervention should be made at the early stage. Therefore, identifying biomarkers for the clinical diagnosis is critical. Metabolomics, a novel "omics", uses methods based on low-molecular-weight molecules, with high-throughput evaluation of a large number of metabolites that may lead to the identification of new disease-specific biomarkers and the elucidation of pathophysiological mechanisms. This review discusses metabolomics investigations of AD and potential future developments in this field.