Cholesterol-induced production of amyloid beta (Abeta) as a putative neurotoxin in Alzheimer's disease (AD), along with epidemiological evidence, suggests that statin drugs may provide benefit in treatment of the disorder. We tested the effect of once daily atorvastatin calcium (80 mg; two 40 mg tablets) on cognitive and/or behavioral decline in patients with mild-to-moderate AD. The study was designed as a pilot intention-to-treat, proof-of-concept, double-blind, placebo-controlled, randomized (1:1) trial with a 1-year exposure to study medication employing last-observation-carried-forward (LOCF) ANCOVA as the primary statistical method of assessment. Alternate statistical methods were employed to further explore the effect of atorvastatin treatment on progression of deterioration. Of the 98 individuals with mild-to-moderate AD (Mini-Mental State Examination score of 12-28) providing Informed Consent, 71 were eligible for randomization, 67 were randomized and 63 completed the 3-month visit and were statistically evaluable. The primary outcome measures were change in the Alzheimer Disease Assessment Scale-Cognitive (ADAS-cog) performance and the Clinical Global Impression of Change (CGIC). Secondary outcome measures included the MMSE, Geriatric Depression Scale (GDS), the Neuropsychiatric Inventory (NPI) and the ADCS Activities of Daily Living inventory (ADCS-ADL). Tertiary outcome measures included levels of total circulating cholesterol, LDL and VLDL, and circulating activity of the free radical scavenger enzymes superoxide dismutase (SOD) and glutathione peroxidase (GpX). Atorvastatin reduced circulating cholesterol levels and produced a positive signal on each of the clinical outcome measures compared to placebo, but did not elicit a difference in circulating SOD or GpX activities. The observed beneficial clinical effect reached significance for the GDS (p = 0.040) and the ADAS-cog at 6 months (p = 0.003), was all but significant for the ADAS-cog (p = 0.055) at 12 months, and was of marginal significance for the CGIC (p = 0.073) and NPI (p = 0.071) at 12 months when employing the primary statistical approach (ANCOVA with LOCF). Application of repeated measures ANCOVA statistics revealed the difference was significant for the CGIC and marginally significant for the ADAS-cog, but not significant for the other clinical indices. This evaluation indicated significant time-by-treatment interactions (altered progression) for the ADAS-cog and MMSE, but not the CGIC. Application of random intercept regression analysis revealed a significant difference for the CGIC, ADAS-cog and MMSE. Regression analysis also indicated that atorvastatin produced change in the slope of deterioration on the MMSE. Accordingly, atorvastatin therapy may be an effective treatment and may slow the progression of AD among mild-to-moderately affected patients.
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http://dx.doi.org/10.2174/1567205054367900 | DOI Listing |
Int J Stroke
January 2025
Department of Neurosurgery and Interventional Neuroradiology, Xuanwu Hospital, China International Neuroscience Institute, Capital Medical University, National Center for Neurological Disorders, 45 Changchun St, Beijing 100053, China.
Rationale: The Chemical Optimization of Cerebral Embolectomy (CHOICE) trial suggested that the administration of intra-arterial alteplase after successful endovascular thrombectomy (EVT) may improve neurological outcomes in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO) in the anterior circulation. However, the use of adjunctive intra-arterial alteplase following successful EVT in acute posterior circulation stroke remains unexplored.
Aims: This study aims to investigate the efficacy and safety of intra-arterial alteplase after successful EVT for AIS-LVO in the posterior circulation.
Int J Gynaecol Obstet
January 2025
Department of Obstetrics and Gynaecology, Hamdard Institute of Medical Sciences and Research, Jamia Hamdard, Delhi, India.
Objective: This study compares ambulatory glycemic profile and glycemic variability between pregnant women diagnosed with type 2 diabetes mellitus (T2DM) receiving pharmacotherapy and healthy pregnant women without diabetes and assesses their correlation with fetal outcome.
Method: This was a case-control study involving 60 pregnant women (40 with T2DM and 20 healthy controls) in the third trimester of pregnancy. A flash glucose monitor device was applied over the upper arm to obtain the ambulatory glucose profile.
Am J Sports Med
January 2025
Department of Sports Medicine, Peking University Third Hospital; Institute of Sports Medicine of Peking University; Beijing Key Laboratory of Sports Injuries, Beijing, China.
Background: There is a lack of evidence and continuous debate on whether femoral tunnel displacement substantially influences the clinical efficacy of medial patellofemoral ligament reconstruction (MPFL-R) in addressing recurrent patellar dislocation.
Purpose: To investigate possible associations between inaccurate femoral tunnel placement during MPFL-R and clinical outcomes, with a specific focus on proximal tunnel malpositioning.
Study Design: Cohort study; Level of evidence, 3.
Clin Transl Allergy
January 2025
Institute of Allergology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Background: Patient-reported outcome measures (PROMs) help to assess disease control and quality of life (QoL) in chronic spontaneous urticaria (CSU) and recurrent angioedema (RA). This study aimed to assess the correlation between two different concepts: disease control and QoL, using disease-specific PROMs.
Methods: We analyzed data from 445 CSU and 330 RA patients who completed both a disease control and QoL PROM as part of the clinical routine.
BMC Med Educ
January 2025
Division of Learning and Teaching, Charles Sturt University, Bathurst, NSW, Australia.
Background: Interviewers' judgements play a critical role in competency-based assessments for selection such as the multiple-mini-interview (MMI). Much of the published research focuses on the psychometrics of selection and the impact of rater subjectivity. Within the context of selecting for entry into specialty postgraduate training, we used an interpretivist and socio-constructivist approach to explore how and why interviewers make judgments in high stakes selection settings whilst taking part in an MMI.
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