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Background: Lipid-lowering therapies are mainstays in reducing recurrence after acute ischemic stroke (AIS). Evolocumab, a Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor, is a promising lipid-lowering agent known to decrease LDL cholesterol and mitigate vascular events alongside statins. However, its effects on the early functional outcomes post-mechanical thrombectomy (MT) remain unclear. This study aimed to assess the short-term effects and incidence of bleeding events after the early, off-label use of PCSK9 inhibitors in AIS patients undergoing MT. Methods: We retrospectively analyzed patients who had MT at a Regional Stroke Center from December 2018 to April 2023. Our primary outcome was discharge functional outcomes. Secondary outcomes included early neurologic deterioration (END), symptomatic intracerebral hemorrhage (sICH), 3-month functional outcomes, 3-month recurrence rate, and lipid profiles. Results: Of 261 patients (mean age 69.2 ± 11.7, men 42.9%), 42 were administered evolocumab peri-procedurally. While baseline characteristics were similar between the two groups, evolocumab group demonstrated improved discharge outcomes, with a lower mean NIHSS (8.8 ± 6.8 vs. 12.4 ± 9.8, p = 0.02) and a higher percentage of patients with discharge mRS ≤ 3 (52.4% vs. 35.6%, p = 0.041). The 3-month follow-up show a non-significant trend toward an improved outcome in the evolocumab group. Multivariable analysis indicated that evolocumab had a potential impact on favorable discharge outcomes (aOR 1.98[0.94-4.22] for mRS ≤ 3 and 0.47[0.27-0.84] for lower ordinal mRS). Notably, evolocuamb users exhibited fewer instances of END and sICH, although they do not reach statistical significance. Additionally, the evolocumab group demonstrated potential benefits in LDL cholesterol reduction over time. Conclusion: Early use of evolocumab in AIS patients undergoing MT appeared to be safe and associated with better early functional outcomes. The potential benefit of the PCSK9 inhibitor shown here warrants further prospective studies.
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BACKGROUND AND PURPOSE: Early- and late-onset Alzheimer's disease (EOAD and LOAD, respectively) share the same neuropathological hallmarks of amyloid and neurofibrillary tangles but have distinct cognitive features. We compared structural brain connectivity between the EOAD and LOAD groups using structural network efficiency and evaluated the association of structural network efficiency with the cognitive profile and pathological markers of Alzheimer's disease (AD). METHODS: The structural brain connectivity networks of 80 AD patients (47 with EOAD and 33 with LOAD) and 57 healthy controls were reconstructed using diffusion-tensor imaging. Graph-theoretic indices were calculated and intergroup differences were evaluated. Correlations between network parameters and neuropsychological test results were analyzed. The correlations of the amyloid and tau burdens with network parameters were evaluated for the patients and controls. RESULTS: Compared with the age-matched control group, the EOAD patients had increased global path length and decreased global efficiency, averaged local efficiency, and averaged clustering coefficient. In contrast, no significant differences were found in the LOAD patients. Locally, the EOAD patients showed decreases in local efficiency and the clustering coefficient over a wide area compared with the control group, whereas LOAD patients showed such decreases only within a limited area. Changes in network parameters were significantly correlated with multiple cognitive domains in EOAD patients, but only with Clinical Dementia Rating Sum-of-Boxes scores in LOAD patients. Finally, the tau burden was correlated with changes in network parameters in AD signature areas in both patient groups, while there was no correlation with the amyloid burden. CONCLUSIONS: The impairment of structural network efficiency and its effects on cognition may differ between EOAD and LOAD.