▶ Treadmill exercise ameliorates cognitive deficits in Tg mice. ▶ Treadmill exercise reduces Aβ-42 and tau deposition in Tg mice. ▶ Treadmill exercise reduces the number of TUNEL-positive cells in Tg ...mice. ▶ Treadmill exercise reduces TC, insulin, glucose, and corticosterone levels in Tg mice. ▶ Treadmill exercise may be beneficial in prevention or treatment in AD.
The present study was undertaken to further investigate the protective effect of treadmill exercise on the hippocampal proteins associated with neuronal cell death in an aged transgenic (Tg) mice with Alzheimer's disease (AD). To address this, Tg mouse model of AD, Tg-NSE/PS2m, which expresses human mutant PS2 in the brain, was chosen. Animals were subjected to treadmill exercise for 12 weeks from 24 months of age. The exercised mice were treadmill run at speed of 12
m/min, 60
min/day, 5 days/week on a 0% gradient for 3 months. Treadmill exercised mice improved cognitive function in water maze test. Treadmill exercised mice significantly reduced the expression of Aβ-42, Cox-2, and caspase-3 in the hippocampus. In parallel, treadmill exercised Tg mice decreased the phosphorylation levels of JNK, p38MAPK and tau (Ser404, Ser202, Thr231), and increased the phosphorylation levels of ERK, PI3K, Akt and GSK-3α/β. In addition, treadmill exercised Tg mice up-regulated the expressions of NGF, BDNF and phospho-CREB, and the expressions of SOD-1, SOD-2 and HSP-70. Treadmill exercised Tg mice up-regulated the expression of Bcl-2, and down-regulated the expressions of cytochrome c and Bax in the hippocampus. The number of TUNEL-positive cells in the hippocampus in mice was significantly decreased after treadmill exercise. Finally, serum TC, insulin, glucose, and corticosterone levels were significantly decreased in the Tg mice after treadmill exercise. As a consequence of such change, Aβ-dependent neuronal cell death in the hippocampus of Tg mice was markedly suppressed following treadmill exercise. These results strongly suggest that treadmill exercise provides a therapeutic potential to inhibit both Aβ-42 and neuronal death pathways. Therefore, treadmill exercise may be beneficial in prevention or treatment of AD.
Objective
The effect of clonal hematopoiesis of indeterminate potential (CHIP) on the manifestation and clinical outcomes of acute ischemic stroke (AIS) has not been fully elucidated.
Methods
...Patients with AIS were included from a prospective registry coupled with a DNA repository. Targeted next‐generation sequencing on 25 genes that are frequently mutated in hematologic neoplasms was performed. The prevalence of CHIP was compared between patients with AIS and age‐matched healthy individuals. A multivariate linear or logistic regression model was used to assess the association among CHIP and stroke severity, hemorrhagic transformation, and functional outcome at 90 days.
Results
In total, 380 patients with AIS (mean age = 67.2 ± 12.7 years; 41.3% women) and 446 age‐matched controls (mean age = 67.2 ± 8.7 years; 31.4% women) were analyzed. The prevalence of CHIP was significantly higher in patients with AIS than in the healthy controls (29.0 vs 22.0%, with variant allele frequencies of 1.5%, p = 0.024). PPM1D was found to be most significantly associated with incident AIS (adjusted odds ratio aOR = 7.85, 95% confidence interval CI = 1.83–33.63, p = 0.006). The presence of CHIP was significantly associated with the initial National Institutes of Health Stroke Scale (NIHSS) score (β = 1.67, p = 0.022). Furthermore, CHIP was independently associated with the occurrence of hemorrhagic transformation (65/110 clonal hematopoiesis positive CH+ vs 56/270 CH negative CH‐, aOR = 5.63, 95% CI = 3.24–9.77, p < 0.001) and 90‐day functional disability (72/110 CH+ vs 99/270 CH‐, aOR = 2.15, 95% CI = 1.20–3.88, p = 0.011).
Interpretation
CH was significantly associated with incident AIS. Moreover, particularly, sequence variations in PPM1D, TET2, and DNMT3A represent a new prognostic factor for AIS. ANN NEUROL 2023;94:836–847
Post-stroke depression (PSD), a prevalent complication of stroke, causes poor outcomes. However, little is known about its prevalence and management among community-dwelling stroke survivors. Thus, ...we investigated the prevalence, awareness, and treatment of PSD in a community setting. A cross-sectional study was performed using representative data from the Korea National Health and Nutrition Surveys 2014, 2016, and 2018. A total of 11,122 participants aged ≥ 40 years were categorized, including 343 stroke survivors and 10,779 non-stroke survivors. We then calculated and compared the prevalence, awareness (formal diagnosis of depression by a doctor), and treatment rates of depression between the two groups. Depression was defined as a score ≥ 10 in the nine-item Patient Health Questionnaire (PHQ-9). Depression was significantly more prevalent among stroke survivors than in non-stroke survivors (22.2% vs. 8.5%, respectively), while the differences in the awareness and treatment rates were insignificant. However, only 46.8% of stroke survivors with PSD were aware of their condition, and only 20.5% were receiving treatment. These results suggest that clinicians should more actively screen for and treat depression among stroke survivors.
Previous studies have reported that early hospital arrival improves clinical outcomes in patients with acute ischemic stroke; however, whether early arrival is associated with favorable outcomes ...regardless of reperfusion therapy and the type of stroke onset time is unclear. Thus, we investigated the impact of onset-to-door time on outcomes and evaluated the predictors of pre-hospital delay after ischemic stroke.
Consecutive acute ischemic stroke patients who arrived at the hospital within five days of onset from September 2019 to May 2020 were selected from the prospective stroke registries of Seoul National University Hospital and Chung-Ang University Hospital of Seoul, Korea. Patients were divided into early (onset-to-door time, ≤4.5 h) and late (>4.5 h) arrivers. Multivariate analyses were performed to assess the effect of early arrival on clinical outcomes and predictors of late arrival.
Among the 539 patients, 28.4% arrived early and 71.6% arrived late. Early hospital arrival was significantly associated with favorable outcomes (three-month modified Rankin Scale mRS: 0-2, adjusted odds ratio aOR: 2.03, 95% confidence interval: CI 1.04-3.96) regardless of various confounders, including receiving reperfusion therapy and type of stroke onset time. Furthermore, a lower initial National Institute of Health Stroke Scale (NIHSS) score (aOR: 0.94, 95% CI: 0.90-0.97), greater pre-stroke mRS score (aOR: 1.58, 95% CI: 1.18-2.13), female sex (aOR: 1.71, 95% CI: 1.14-2.58), unclear onset time, and ≤6 years of schooling (aOR: 1.76, 95% CI: 1.03-3.00 compared to >12 years of schooling) were independent predictors of late arrival.
Thus, the onset-to-door time of≤4.5 h is crucial for better clinical outcome, and lower NIHSS score, greater pre-stroke mRS score, female sex, unclear onset times, and ≤6 years of schooling were independent predictors of late arrival. Therefore, educating about the importance of early hospital arrival after acute ischemic stroke should be emphasized. More strategic efforts are needed to reduce the prehospital delay by understanding the predictors of late arrival.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background and purpose
Although it is not recognized as essential to test for antiphospholipid antibody (aPL) in stroke of unknown cause, aPL‐related stroke may account for a considerable number of ...cryptogenic strokes. We aimed to assess the current status and diagnostic value of aPL testing in cryptogenic stroke patients.
Methods
Consecutive patients admitted with acute ischemic stroke were examined to confirm the factors associated with performing aPL testing and with positive aPL test results in real‐world practice. Cryptogenic stroke patients were separately examined in the same manner. The antibody profiles of cryptogenic stroke patients with aPL positivity were compared by age.
Results
Among 2947 patients, 606 (20.6%) were tested for aPLs and 129 (21.3%) were positive. Physicians tended to perform aPL testing in patients aged <50 years and in cryptogenic stroke patients. Cryptogenic stroke was a strong predictor of positive aPL results (adjusted odds ratio 3.70, 95% confidence interval 2.38–5.76). However, aPL positivity did not differ by age in stroke patients. Among 283 cryptogenic stroke patients, 136 (48.1%) were tested for aPLs and 56 (41.2%) were positive. aPL tests were performed predominantly in patients aged <50 years rather than in older patients, even among cryptogenic stroke patients. The two age groups had similar positivity rates of >40% (<50 years: 43.2%; ≥50 years: 40.4%; p = 0.92) and their antibody profiles were similar.
Conclusions
A significant number of patients with cryptogenic stroke had positive aPL results regardless of age. aPL testing may offer additional diagnostic opportunities in cryptogenic stroke patients, and thus may reduce the incidence of cryptogenic stroke.
The test positivity rates of antiphospholipid (aPL) antibody of cryptogenic stroke patients were consistently high across ages, nevertheless, aPL tests were predominantly performed in patients aged <50 years with cryptogenic stroke and more than half of cryptogenic stroke patients aged ≥50 years remained untested, leaving diagnostic uncertainty. The results of this study may imply that aPL testing should be performed in all cryptogenic stroke patients, regardless of age.
The coronavirus disease 2019 (COVID-19) pandemic has greatly altered the daily lives of people in unprecedented ways, causing a variety of mental health problems. In this study, we aimed to evaluate ...the prevalence of depression among Korean adults during the COVID-19 pandemic and explore the factors associated with depressive mood using data from the Korea National Health and Nutrition Survey (KNHANES).
We analyzed participants aged ≥ 19 years from KNHANES 2018 (n = 5,837) and 2020 (n = 5,265) to measure and compare the prevalence of depression before and during the COVID-19 pandemic. Depression was defined as a score ≥ 10 on the Patient Health Questionnaire-9. Furthermore, we performed a multivariate logistic regression analysis to investigate the independent predictors of depressive mood during the COVID-19 pandemic.
The prevalence of depression was notably higher during the COVID-19 pandemic than in the pre-pandemic period (5.2% vs. 4.3%,
= 0.043). In a multivariate model, female sex (adjusted odds ratio aOR, 1.63; 95% confidence interval CI, 1.10-2.41), age < 50 years (19-29 years: aOR, 7.31; 95% CI, 2.40-22.21; 30-39 years: aOR, 7.38; 95% CI, 2.66-20.47; 40-49 years: aOR, 4.94; 95% CI, 1.84-13.31 compared to ≥ 80 years), unemployment (aOR, 2.00; 95% CI, 1.41-2.85), upper-middle class household income (aOR, 1.83; 95% CI, 1.18-2.85 compared to upper-class income), being a beneficiary of Medicaid (aOR, 2.35; 95% CI, 1.33-4.14), poor self-rated health (aOR, 4.99; 95% CI, 1.51-3.47 compared to good self-rated health), and current smoking (aOR, 2.29; 95% CI, 1.51-3.47) were found to be significant risk factors for depression during the pandemic.
Depression was significantly more prevalent among Korean adults during the COVID-19 pandemic than in the pre-pandemic era. Therefore, more attention should be paid to individuals vulnerable to depression during pandemics. Implementing psychological support public policies and developing interventions to prevent the adverse outcomes of COVID-19-related depression should be considered.
Patients with stroke may develop hyperperfusion after a successful endovascular thrombectomy (EVT). However, the relationship between post-EVT hyperperfusion and clinical outcomes remains unclear and ...requires further clarification. We reviewed consecutive patients with anterior circulation occlusion who were successfully recanalized with EVT. Based on post-EVT arterial spin-labeling images, hyperperfusion was categorized as follows: global hyperperfusion (GHP), increased cerebral blood flow (CBF) in ≥ 50% of the culprit vessel territory; focal hyperperfusion (FHP), increased CBF in < 50% of the culprit vessel territory; no hyperperfusion (NHP), no discernible CBF increase. Factors associated with hyperperfusion were assessed, and clinical outcomes were compared among patients under different hyperperfusion categories. Among 131 patients, 25 and 40 patients developed GHP and FHP, respectively. Compared to other groups, the GHP group had worse National Institutes of Health Stroke Scale score (GHP vs. NHP/FHP, 18.1 ± 7.4 vs. 12.3 ± 6.0; p < 0.001), a larger post-EVT infarct volume (98.9 42.3-132.7 vs. 13.5 5.0-34.1 mL; p < 0.001), and a worse 90-day outcome (modified Rankin Scale, 3 1-4 vs. 2 0-3; p = 0.030). GHP was independently associated with infarct volume (B = 0.532, standard error = 0.163, p = 0.001), and infarct volume was a major mediator of the association of GHP with unfavorable outcomes (total effect: β = 0.176, p = 0.034; direct effect: β = 0.045, p = 0.64; indirect effect: β = 0.132, p = 0.017). Patients presenting with post-EVT GHP had poorer neurological prognosis, which is likely mediated by a large infarct volume.
Family history (FH) is one of important risk factors for cardiovascular disease (CVD). However, little is known about its impact on dyslipidemia prevalence and management status. Thus, we aimed to ...investigate the impact of FH of CVD on dyslipidemia prevalence, awareness, treatment, control, and healthy behaviors in Korean adults.
We conducted a cross-sectional study using representative data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2014-2018. A total of 22,024 participants aged ≥ 19 years without histories of CVDs were classified into two groups according to the presence of FH of CVD (with FH, n = 3,778; without FH, n = 18,246). FH of CVD was defined as having a first-degree relative with ischemic heart disease or stroke. Multivariate logistic regression analyses were performed to evaluate the association between FH of CVD and dyslipidemia prevalence, awareness, treatment, control, and healthy behaviors (weight control, non-smoking, non-risky drinking, sufficient physical activity, and undergoing health screening).
FH of CVD was significantly associated with a higher dyslipidemia prevalence (adjusted odds ratio aOR 1.34, 95% confidence interval CI 1.18-1.51), better awareness (aOR 1.54, 95%CI 1.19-2.00), and treatment rates (aOR 1.34, 95%CI 1.12-1.60), but not control. Having an FH of CVD was not predictive of any healthy behaviors in dyslipidemia patients. For non-dyslipidemia patients, FH of CVD even showed significant association with smoking (aOR 1.18, 95%CI 1.02-1.36), and risky drinking (aOR 1.20, 95%CI 1.03-1.40) while it was predictive of receiving health screening (aOR 1.14, 95% CI 1.02-1.27).
Having an FH of CVD might positively trigger dyslipidemia patients to start pharmacological intervention, but not non-pharmacological interventions. Therefore, physicians should make more efforts to educate and promote the importance of non-pharmacological behavioral modification in dyslipidemia patients with an FH of CVD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We tried to investigate the effect of non-persistence with antiplatelets after ischemic stroke on long-term all-cause mortality (ACM).
We selected newly diagnosed ischemic stroke patients aged ...≥20years who were newly treated with aspirin or clopidogrel from 2003-2010 Korean National Health Insurance Service-National Sample Cohort, a random sample of 2.2% of total population. Subjects were divided into two pairs of groups according to persistence with antiplatelets at 6 and 12 months: those who discontinued antiplatelets within 6 months (DA6M) and those who continued them for 6 or months or more (CA6M); and those who discontinued antiplatelets within 12 months (DA12M) and those who continued them for 12 months or more (CA12M). Those who died within 6 months among DA6M and those who died within 12 months among DA12M were excluded along with those with medication possession ratio<80% among CA6M and CA12M. Subjects were followed-up until death or December 31, 2013. Among 3,559 total subjects, DA6M were 1,080 and CA6M were 2,479 while, out of 3,628 total patients, DA12M were 1,434 and CA12M were 2,194. The risks of ACM adjusted hazard ratio (aHR), 2.25; 95% confidence interval (CI), 1.94-2.61, cerebro-cardiovascular disease (CVD) death (aHR, 2.52; 95% CI, 1.96-3.24) and non-CVD death (aHR, 2.11; 95% CI, 1.76-2.64) of DA6M were all significantly increased compared to CA6M. DA12M also had significantly higher risks of ACM (aHR, 1.93; 95% CI, 1.65-2.25), CVD mortality (aHR, 2.13; 95% CI; 1.63-2.77) and non-CVD mortality (aHR, 1.83;95% CI 1.51-2.22) than DA12M but aHRs were lower than that between DA6M and CA6M. The difference rates of ACM, CVD death, and non-CVD death between non-persistent and persistent groups all continuously widened over time but the degree of difference was gradually decreased.
Maintaining antiplatelets for the first 12 months after ischemic stroke reduces long-term risks of both CVD death and non-CVD death.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We tried to evaluate the prevalence of premature discontinuation of antiplatelets and its affecting factors after ischemic stroke using large-sized representative national claims data.
Patients aged ...20 years or older with newly confirmed ischemic stroke who started aspirin or clopidogrel for the first time were selected from 2003 to 2010 National Health Insurance Service-National Sample Cohort (NHIS-NSC) of South Korea (n = 4621), a randomly collected sample which accounts for 2.2% (n = 1,017,468) of total population (n = 46,605,433). The prevalence of discontinuation of antiplatelets was measured every 6 months until the 24 months since the first prescription. Then we classified the participants into 2 groups according to the discontinuation status at 12 months and assessed the factors influencing premature discontinuation of antiplatelets within 12 months.
Among total participants, 35.5% (n = 1640) discontinued antiplatelets within 12 months and 58.5% (n = 2704) discontinued them within 24 months. The remaining 41.5% (n = 1917) continued them for 24 months or more. In the multivariate logistic regression analysis, initiating treatment with aspirin monotherapy adjusted OR (aOR), 2.66, 95% CI 2.17-3.25 was the most prominent determinant of premature discontinuation within 12 months followed by CCI score ≥ 6 (aOR 1.50, 95% CI 1.31-1.98), and beginning treatment with clopidogrel monotherapy (aOR 1.41, 95% CI 1.15-1.72). Rural residency (aOR 1.36, 95% CI 1.14-1.62), < 4 total prescribed drugs (aOR 1.24, 95% CI 1.05-1.47), lower income (aOR 1.20, 95% CI 1.03-1.40 for middle income class and OR 1.21, 95% CI 1.02-1.45 for low income class), and ages ≥70 years (aOR 1.15, 95% CI 1.00-1.31) were also significantly associated with premature discontinuation of antiplatelets within 12 months.
The prevalence of premature discontinuation of antiplatelets after ischemic stroke was quite high. Thus, by understanding factors associated with premature discontinuation, a more strategic approach is required for the physicians to improve persistence with antiplatelets.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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