Dual Antiplatelet Therapy and Outcomes in Acute Mild to Moderate Stroke With Versus Without Large-Artery Atherosclerosis Post Hoc Analysis of ATAMIS.

BACKGROUND: We conducted a post hoc analysis of the ATAMIS (Antiplatelet Therapy in Acute Mild to Moderate Ischemic Stroke) trial to investigate whether the priority of clopidogrel plus aspirin to aspirin alone was consistent between patients with and without stroke pathogenesis of large-artery atherosclerosis (LAA). METHODS AND RESULTS: Patients with stroke classification randomized to a clopidogrel-plus-aspirin group and aspirin-alone group in a modified intention-to-treat analysis set of ATAMIS were classified into LAA and non-LAA subtypes. The primary outcome was early neurologic deterioration at 7 days, defined as a >2-point increase in National Institutes of Health Stroke Scale score compared with baseline, and safety outcomes were bleeding events and intracranial hemorrhage. We compared treatment effects in each stroke subtype and investigated the interaction. Among 2910 patients, 225 were assigned into the LAA subtype (119 in the clopidogrel-plus-aspirin group and 106 in the aspirin-alone group) and 2685 into the non-LAA subtype (1380 in the clopidogrel-plus-aspirin group and 1305 in the aspirin-alone group). Median age was 66 years, and 35% were women. A lower proportion of early neurologic deterioration was found to be associated with dual antiplatelet therapy in the LAA subtype (adjusted risk difference, -10.4% [95% CI, -16.2% to -4.7%]; P=0.001) but not in the non-LAA subtype (adjusted risk difference, -1.4% [95% CI, -2.6% to 0.1%]; P=0.06). No significant interaction was found (P=0.11). CONCLUSIONS: Compared with the non-LAA subtype, patients with stroke of the LAA subtype may get more benefit from dual antiplatelet therapy with clopidogrel plus aspirin with respect to early neurologic deterioration at 7 days. REGISTRATION: URL: clinicaltrials.gov; UnIque identifier: NCT02869009.

A nomogram for predicting cerebral white matter lesions in elderly men.

Objective: This study aimed to develop a nomogram tool to predict cerebral white matter lesions (WMLs) in elderly men. Methods: Based on a retrospective cohort from January 2017 to December 2019, a multivariate logistic analysis was performed to construct a nomogram for predicting WMLs. The nomogram was further validated using a follow-up cohort between January 2020 and December 2022. The calibration curve, receiver operating characteristics (ROC) curves, and the decision curves analysis (DCA) were used to evaluate discrimination and calibration of this nomogram. Result: A total of 436 male patients were enrolled in this study, and all 436 patients were used as the training cohort and 163 follow-up patients as the validation cohort. A multivariate logistic analysis showed that age, cystatin C, uric acid, total cholesterol, platelet, and the use of antiplatelet drugs were independently associated with WMLs. Based on these variables, a nomogram was developed. The nomogram displayed excellent predictive power with the area under the ROC curve of 0.951 [95% confidence interval (CI), 0.929-0.972] in the training cohort and 0.915 (95% CI, 0.864-0.966) in the validation cohort. The calibration of the nomogram was also good, as indicated by the Hosmer-Lemeshow test with p-value of 0.594 in the training cohort and 0.178 in the validation cohort. The DCA showed that the nomogram holds good clinical application value. Conclusion: We have developed and validated a novel nomogram tool for identifying elderly men at high risk of WMLs, which exhibits excellent predictive power, discrimination, and calibration.

Remote Ischemic Conditioning and Outcomes in Acute Ischemic Stroke With Versus Without Large Artery Atherosclerosis.

BACKGROUND: RICAMIS trial (The Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke) has demonstrated efficacy of remote ischemic conditioning (RIC) in acute ischemic stroke. We conducted a post hoc analysis of RICAMIS to investigate whether large artery atherosclerosis (LAA) subtype contributed to the outcomes. METHODS: This is a post hoc analysis of the RICAMIS trial. Patients randomized to RIC group and Control group in full analysis set of RICAMIS were classified into LAA and non-LAA subtypes. The primary outcome was excellent functional outcome at 90 days, defined as modified Rankin Scale score of 0 to 1. Compared with patients receiving usual care, we investigated the association of RIC effect with outcomes in stroke subtypes and the interaction between RIC effect and stroke subtypes. The primary analysis was adjusted analysis. RESULTS: Among 1773 patients, 516 were assigned to LAA subtype (229 in the RIC group and 287 in the control group) and 1257 to non-LAA subtype (633 in the RIC group and 624 in the control group). Median age was 65 years, and 34.2% were women. A higher proportion of primary outcome was found to be associated with RIC treatment in LAA subtype (adjusted risk difference, 11.4% [95% CI, 3.6%-19.2%]; P=0.004), but not in non-LAA subtype (adjusted risk difference, 4.1% [95% CI, -1.1% to 9.3%]; P=0.12). There was no significant interaction between RIC effect and stroke subtypes (P=0.12). CONCLUSIONS: Patients with LAA subtype may benefit from RIC after stroke with respect to excellent functional outcome at 90 days. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03740971.

MRI-based risk stratification for recurrent ischemic stroke in embolic stroke of undetermined source.

OBJECTIVE: Leukoaraiosis and other brain MRI-assessed parameters were shown to be associated with recurrent stroke in this population. We aimed to develop an MRI-based predictive tool for risk stratification of ESUS patients. METHODS: We retrospectively assessed consecutive patients who were diagnosed with ESUS and underwent brain MRI and performed a multivariable analysis with the outcome of recurrent stroke/TIA. Based on the coefficient of each covariate, we generated an integer-based point scoring system. The discrimination and calibration of the score were assessed using the area under the receiver operator characteristic curve, net reclassification improvement, integrated discrimination improvement, calibration curve, and decision curve analysis. Also, we compared the new score with a previously published score (ALM score). RESULTS: Among 176 patients followed for an overall period of 902.3 patient-years (median of 74 months), there were 39 recurrent ischemic stroke/TIAs (4.32 per 100 patient-years). Fazekas score (HR: 1.26, 95% CI: 1.03-1.54), enlarged perivascular space (EPVS) (HR: 2.76, 95% CI: 1.12-6.17), NIHSS at admission (HR: 1.11, 95% CI: 1.02-1.18), and infarct subtypes (HR: 2.88, 95% CI: 1.34-6.17) were associated with recurrent stroke/TIA. Accordingly, a score (FENS score) was developed with AUC-ROC values of 0.863, 0.788, and 0.858 for 1, 3, and 5 years, respectively. These were significantly better than the AUC-ROC of ALM score (0.635, 0.695, and 0.705, respectively). The FENS score exhibited better calibration and discrimination ability than the ALM score (Hosmer-Lemeshow test χ2 : 4.402, p = 0.819). CONCLUSION: The MRI-based FENS score can provide excellent predictive performance for recurrent stroke/TIA and may assist in risk stratification of ESUS patients.

Long-term atorvastatin improves cognitive decline by regulating gut function in naturally ageing rats.

BACKGROUND: Statins have been widely used to prevent cardiovascular disease in middle-aged and elderly populations; however, the effect of long-term treatment on cognitive function is controversial. To simulate clinical conditions, middle-aged rats were given atorvastatin for 9 consecutive months to investigate the effect on natural cognitive decline and the possible mechanisms. RESULTS: The results showed that compared with the control group, long-term atorvastatin treatment naturally improved cognitive decline. Furthermore, long-term treatment regulated intestinal retinoic acid (RA) metabolism and storage by altering retinol dehydrogenase 7 (Rdh7) expression in the intestine, while RA metabolism affected the proliferation of intestinal Treg cells and inhibited IL-17+γδ T-cell function. In addition, long-term atorvastatin increased intestinal flora richness and decreased IL-17 expression in hippocampal tissue. CONCLUSION: Collectively, these findings provide the first evidence that long-term atorvastatin intervention may prevent cognitive decline in naturally ageing rats by inhibiting neuroinflammation via the gut-brain axis.

Deciphering Age Differences in Experience-Based Decision-Making: The Role of Sleep.

OBJECTIVE: Recent studies have demonstrated that sleep not only facilitates memory consolidation but also benefits more complex cognitive skills such as decision-making in young adults. Older adults use different decision strategies compared with young adults, which leaves the role of sleep in older adults' decision-making unclear. We investigated the age-by-sleep effect on decision-making. METHODS: We recruited 67 young adults (ages 18 to 29 years) and 66 older adults (ages 60 to 79 years) and randomly assigned them into the "sleep" or "wake" study condition. They were given a modified Iowa gambling task to perform before and after a 12-hour interval with sleep or wakefulness. RESULTS: Using the typical model-free analysis, we found that young adults' between-session performance improved greater than that of older adults regardless of the sleep/wake condition. Furthermore, older adults with longer total sleep time showed a greater improvement in the selection of one "good" deck. To further examine the sleep effect on age-related differences in cognitive processes underlying decision-making, we conducted computational modelling. This more fine-grained analysis revealed that sleep improved feedback sensitivity for both young and older adults while it increased loss aversion for older adults but not for young adults. CONCLUSION: These findings indicate that sleep promotes learning-based decision-making performance via facilitating value representation, and such modulation is distinct in young compared to older adults.