Although ankle–brachial index (ABI), an indicator of atherosclerosis or arterial stiffness, has been associated with dementia and Alzheimer’s disease (AD), no information is yet available for its contribution to AD pathologies. We investigated the relationship between the ABI and in vivo β-amyloid (Aβ) deposition and AD-specific neurodegeneration in cognitively normal (CN) elderly individuals. A total of 256 CN elderly subjects who participated in the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE), an ongoing prospective cohort study, were included. All subjects underwent comprehensive clinical and neuropsychological assessments, ABI measurement, apolipoprotein E (APOE) genotyping, [11C]Pittsburgh Compound B (PiB)-positron emission tomography (PET), [18F]-fludeoxyglucose PET, and magnetic resonance imaging. A significant positive association was found between the ABI and global cerebral Aβ retention measured by PiB-PET, even after controlling for age, sex, and APOE ε4. When three stratified ABI subgroups (ABI < 1.00, 1.00–1.29, and ≥ 1.30) were compared, the highest ABI subgroup (ie, ABI ≥ 1.30) showed significantly higher Aβ deposition than that of the other subgroups. This relationship between Aβ deposition and the ABI was significant only in APOE ε4 carriers, but not in noncarriers. No significant association was observed between the ABI and neurodegeneration in the AD-signature regions. Our findings suggest that a high ABI, possibly related to arterial stiffness, is associated with elevated brain Aβ burden in cognitively healthy elderly individuals, particularly in APOE ε4 carriers.
Abstract Several epidemiological and preclinical studies supported the protective effect of coffee on Alzheimer’s disease (AD). However, it is still unknown whether coffee is specifically related with reduced brain AD pathologies in human. Hence, this study aims to investigate relationships between coffee intake and in vivo AD pathologies, including cerebral beta-amyloid (Aβ) deposition, the neurodegeneration of AD-signature regions, and cerebral white matter hyperintensities (WMH). A total of 411 non-demented older adults were included. Participants underwent comprehensive clinical assessment and multimodal neuroimaging including [ 11 C] Pittsburgh compound B-positron emission tomography (PET), [ 18 F] fluorodeoxyglucose PET, and magnetic resonance imaging scans. Lifetime and current coffee intake were categorized as follows: no coffee or <2 cups/day (reference category) and ≥2 cups/day (higher coffee intake). Lifetime coffee intake of ≥2 cups/day was significantly associated with a lower Aβ positivity compared to coffee intake of <2 cups/day, even after controlling for potential confounders. In contrast, neither lifetime nor current coffee intake was not related to hypometabolism, atrophy of AD-signature region, and WMH volume. The findings suggest that higher lifetime coffee intake may contribute to lowering the risk of AD or related cognitive decline by reducing pathological cerebral amyloid deposition.
We aimed to examine the feasibility and effectiveness of a multidomain intervention including intensive and maintenance programs for reducing the risk of dementia in at-risk older adults. Community-dwelling older adults (aged ≥60 years) without dementia but having several risk factors for dementia (N = 32; 89% female; mean age±standard deviation, 76.8±4.7 years) were assigned to three parallel programs: intensive plus maintenance (INT+MNT), intensive only (INT-only), and active control. Subjects in INT+MNT and INT-only groups participated in a 4-week intensive group-based lifestyle modification program that focused on physical activity, vascular risk factors, dietary habits, cognitive activities, and social engagement. INT+MNT participants underwent an additional 20-week maintenance program to consolidate modified habits. The modified Australian National University-Alzheimer’s Disease Risk Index (ANU-ADRI) score was used as the primary outcome measure for dementia risk. The changes in ANU-ADRI scores exhibited a significant group-by-time interaction: the INT+MNT group showed significant improvement at 24 weeks (β= –6.05; SE = 1.86; p = 0.002), while the INT-only group did not. Additional exploratory analyses showed that the reduction in ANU-ADRI scores was caused by changes in protective factors rather than in risk factors. The INT + MNT group also showed greater improvement in executive function at 4 and 24 weeks (both p = 0.044), whereas changes in global cognitive function did not reach significance ( p = 0.055). A 24-week multidomain dementia prevention involving a maintenance strategy for sustaining modified lifestyle habits reduced the risk of dementia and improved executive function in at-risk older adults.
Data on dexamethasone, cytarabine, and cisplatin (DHAP) as a mobilization regimen, compared to high-dose cyclophosphamide (HDC), for up-front autologous stem cell transplantation (ASCT) in non-Hodgkin's lymphoma (NHL) is limited.Consecutive patients with aggressive NHL treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or rituximab-CHOP who underwent chemomobilization using HDC or DHAP plus granulocyte-colony stimulating factor (G-CSF) for up-front ASCT were enrolled from three institutions between 2004 and 2014.Ninety-six patients (57 men) were included. Sixty-five patients (67.7%) received HDC; and 31 (32.3%), DHAP. The total CD34+ cells mobilized were significantly higher in patients receiving DHAP (16.1 vs. 6.1 × 106/kg, p = 0.001). More patients achieved successful mobilization with DHAP (CD34+ cells ≥ 5.0 × 106/kg) compared to HDC (87.1% vs. 61.5%, respectively; p = 0.011), particularly within the first two sessions of apheresis (64.5% vs. 32.3%, respectively; p = 0.003). Mobilization failure rate (CD34+ cells < 2.0 × 106/kg) was significantly higher in patients receiving HDC (20.0% vs. 3.2%, p = 0.032). On multivariate analysis, the DHAP regimen (odds ratio, 4.12; 95% confidence interval, 1.12 to 15.17) was an independent predictor of successful mobilization. During chemomobilization, patients receiving HDC experienced more episodes of febrile neutropenia compared to patients receiving DHAP (32.3% vs. 12.9%, p = 0.043).The DHAP regimen was associated with a significantly higher efficacy for stem cell mobilization and lower frequency of febrile neutropenia. Therefore, DHAP plus G-CSF is an effective for mobilization in patients with aggressive NHL who were candidates for up-front ASCT.
4119 Background: Modified FOLFIRINOX (mFOLFIRINOX) consisting of 5-fluorouracil/leucovorin, irinotecan, and oxaliplatin has been assessed as second-line treatment of patients with advanced pancreatic cancer in retrospective and phase II studies. However, the result was not confirmed by randomized controlled trial. Methods: A randomized, open-label, phase III trial was conducted at 9 institutions in Korea. Patients with metastatic pancreatic adenocarcinoma (mPAC) and Eastern Cooperative Oncology Group performance status of 0-1 who failed to first-line gemcitabine-based chemotherapy were randomly assigned to receive mFOLFIRINOX or S-1. The primary endpoint was overall survival. Results: A total of 80 patients were enrolled from March 2017 to December 2019. The accrual of patients was early terminated due to clear difference of efficacy in the interim analysis and expectation of poor recruitment due to conflicting adjuvant regimens. Objective response and disease control rates were 15.4% vs. 2.4% ( p= 0.041) and 66.7% vs. 36.6% ( p= 0.007) in the mFOLFIRINOX and S-1 arms, respectively. The median progression-free survival was 5.2 and 2.2 months in the mFOLFIRINOX and S-1 arms, respectively ( p= 0.002). The median overall survival was 9.2 and 4.9 months in the mFOLFIRINOX and S-1 arms, respectively ( p= 0.048). The adjusted hazard ratio of the mFOLFIRINOX arm to the S-1 arm for overall survival was 0.402 (95% confidence interval 0.223-0.725, p= 0.002). All grade 3-4 adverse events occurred in 56.5% and 17.1% in the mFOLFIRINOX and S-1 arms, respectively ( p< 0.001). However, only one patient in each arm prematurely discontinued treatment due to toxicity and there was no treatment-related mortality in both arms. Minimally important differences in the health-related quality of life were not observed in both arms. Conclusions: mFOLFIRINOX as second-line treatment in mPAC patients failed to gemcitabine-based chemotherapy demonstrated a survival benefit versus S-1 alone with acceptable toxicities. Clinical trial information: KCT0003534.
Objective of the study: Clozapine is one of well-known antipsychotics which causes hematologic adverse effects, specifically neutropenia and agranulocytosis (1-3% of patients).We found a rare case of thrombocytosis and anemia after the re-administration of clozapine.Methods used: We reviewed the documents about clozapine induced hematologic adverse-effects, esp.anemia and thrombocytosis.And we summarized the case of anemia and thrombocytosis after re-start of clozapine by the result of hematologic work-up and clinical responses of it.Summary of results: Reports about blood dyscrasias like anemia and thrombocytosis after clozapine treatment has been extremely rare.In some cases, re-challenge of clozapine could lead to hematopoietic abnormality related to thrombocytopenia or thrombocytosis, which is may be a result of an immune reaction.The details of hematologic finding are shown in the graph.Conclusions reaches: This case report suggest that clinician should monitor platelet count after the re-treatment of clozapine.
The quality of dietary fats is associated with risk of cardiovascular diseases (CVD). We aimed to investigate the association between fatty acids in erythrocyte membrane phospholipids and CVD risk factors in middle-aged Korean adults. Fifty-five middle-aged adults who underwent health examinations were included in this retrospective and cross-sectional study. Anthropometry, serum lipids, clinical parameters, and erythrocyte membrane phospholipid fatty acid data were obtained from a registry. The proportion of C14:0 and C16:0 was greatly elevated in high quartile groups for triglyceride (TG) and systolic and diastolic blood pressure groups (SBP and DBP) (p = 0.042, p = 0.021, or p = 0.008 respectively) compared to low quartile groups. While C16:1n7 and/or C18:1n9 were positively associated with CVD risk factors, the delta 9 desaturase activity index (D9D) (C18:1n9/C18:0) was only significantly increased in high quartile groups for TG and blood pressures (p = 0.001, p = 0.002 or p = 0.003). Conversely, TG and blood pressures showed inverse relationships with C20:4n6 or D5D (C20:4n6/C20:3n6). C18:3n6 and/or D6D (C18:3n6/C18:2n6) were positively associated with insulin resistance and diabetic parameters. Particularly high D6D was detected in high quartile groups of FBS and insulin (p = 0.016 and p = 0.042). In linear regression analysis, D9D and/or C14:0 + C16:0 were significant contributors to serum TG and blood pressures. D6D was a contributing factor to FBS. The indices of D9D and D6D from erythrocyte membrane phospholipids and the proportion of saturated fatty acids were increased as the cardiovascular risk factors, including serum TG, blood pressures, and FBS increased their levels (IRB number C2014199 (1396)).
'%3e%3cg id='b'%3e%3cpath id='a' stroke='%23000' stroke-width='2' d='M-6-25H6m-12 3H6m-12 3H6'/%3e%3cuse xlink:href='%23a' y='44'/%3e%3c/g%3e%3cpath stroke='%23fff' d='M0 17v10'/%3e%3ccircle r='12' fill='%23cd2e3a'/%3e%3cpath fill='%230047a0' d='M0-12A6 6 0 0 0 0 0a6 6 0 0 1 0 12 12 12 0 0 1 0-24z'/%3e%3c/g%3e%3cg transform='rotate(-123.69)'%3e%3cuse xlink:href='%23b'/%3e%3cpath stroke='%23fff' d='M0-23.5v3M0 17v3.5m0 3v3'/%3e%3c/g%3e%3c/svg%3e)
'%3e%3ccircle r='120' fill='%230f47af'/%3e%3cg id='a'%3e%3cpath fill='%23fcdd09' d='m0-96-4.206 12.944 17.348 53.39h-23.13l-2.599 8h74.163l11.011-8H21.553z'/%3e%3cpath stroke='%23fcdd09' stroke-width='4' d='m25.863-35.597 30.564-42.069'/%3e%3c/g%3e%3cuse xlink:href='%23a' transform='rotate(72)'/%3e%3cuse xlink:href='%23a' transform='rotate(144)'/%3e%3cuse xlink:href='%23a' transform='rotate(216)'/%3e%3cuse xlink:href='%23a' transform='rotate(288)'/%3e%3c/g%3e%3c/svg%3e)
