Cumulative data suggest that neuroinflammation plays a prominent role in Alzheimer's disease (AD) pathogenesis. The purpose of this work was to assess if patients with AD present a specific cerebrospinal fluid (CSF) cytokine profile and if it correlates to disease progression. We determined the levels of 27 cytokines in CSF of patients with AD and compared them with patients with frontotemporal dementia and nondemented controls. In addition, we correlated the cytokine levels with cognitive status and disease progression after 12 months. Patients with AD had higher levels of proinflammatory and anti-inflammatory cytokines (eotaxin, interleukin [IL]-1ra, IL-4, IL-7, IL-8, IL-9, IL-10, IL-15, granulocyte colony-stimulating factor, monocyte chemotactic protein 1, platelet-derived growth factor, tumor necrosis factor alfa) compared to nondemented controls. There was a negative correlation between the disease progression and the levels of several cytokines (IL-1b, IL-4, IL-6, IL-9, IL-17A, basic fibroblast growth factor, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interferon gamma, macrophage inflammatory proteins-1b). To the best of our knowledge, this is the first study reporting a "protective" role of the upregulation of specific intrathecal cytokine levels in AD. This finding supports that a fine "rebalancing" of the immune system represents a new target in AD therapeutic approach.
These figures are in keeping with similar studies and emphasize the importance of diagnosis and management of MG in elderly populations. Muscle Nerve 54: 413-421, 2016.
Objectives ANCA-associated vasculitis (AAV) can affect all age groups. We aimed to show that differences in disease presentation and 6 month outcome between younger- and older-onset patients are still incompletely understood. Methods We included patients enrolled in the Diagnostic and Classification Criteria for Primary Systemic Vasculitis (DCVAS) study between October 2010 and January 2017 with a diagnosis of AAV. We divided the population according to age at diagnosis: <65 years or ≥65 years. We adjusted associations for the type of AAV and the type of ANCA (anti-MPO, anti-PR3 or negative). Results A total of 1338 patients with AAV were included: 66% had disease onset at <65 years of age [female 50%; mean age 48.4 years (s.d. 12.6)] and 34% had disease onset at ≥65 years [female 54%; mean age 73.6 years (s.d. 6)]. ANCA (MPO) positivity was more frequent in the older group (48% vs 27%; P = 0.001). Younger patients had higher rates of musculoskeletal, cutaneous and ENT manifestations compared with older patients. Systemic, neurologic,cardiovascular involvement and worsening renal function were more frequent in the older-onset group. Damage accrual, measured with the Vasculitis Damage Index (VDI), was significantly higher in older patients, 12% of whom had a 6 month VDI ≥5, compared with 7% of younger patients (P = 0.01). Older age was an independent risk factor for early death within 6 months from diagnosis [hazard ratio 2.06 (95% CI 1.07, 3.97); P = 0.03]. Conclusion Within 6 months of diagnosis of AAV, patients >65 years of age display a different pattern of organ involvement and an increased risk of significant damage and mortality compared with younger patients.
To develop and validate updated classification criteria for giant cell arteritis (GCA). Methods. Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 6 phases: 1) identification of candidate items, 2) prospective collection of candidate items present at the time of diagnosis, 3) expert panel review of cases, 4) data-driven reduction of candidate items, 5) derivation of a points-based risk classification score in a development data set, and 6) validation in an independent data set.Results. The development data set consisted of 518 cases of GCA and 536 comparators. The validation data set consisted of 238 cases of GCA and 213 comparators. Age ≥50 years at diagnosis was an absolute requirement for classification. The final criteria items and weights were as follows: positive temporal artery biopsy or temporal artery halo sign on ultrasound (+5); erythrocyte sedimentation rate ≥50 mm/hour or C-reactive protein ≥10 mg/liter (+3); sudden visual loss (+3); morning stiffness in shoulders or neck, jaw or tongue claudication, new temporal headache, scalp tenderness, temporal artery abnormality on vascular examination, bilateral axillary involvement on imaging, and fluorodeoxyglucose-positron emission tomography activity throughout the aorta (+2 each). A patient could be classified as having GCA with a cumulative score of ≥6 points. When these criteria were tested in the validation data set, the model area under the curve was 0.91 (95% confidence interval [95% CI] 0.88-0.94) with a sensitivity of 87.0% (95% CI 82.0-91.0%) and specificity of 94.8% (95% CI 91.0-97.4%).Conclusion. The 2022 American College of Rheumatology/EULAR GCA classification criteria are now validated for use in clinical research.This criteria set has been approved by the American College of Rheumatology (ACR) Board of Directors and the EULAR Executive Committee. This signifies that the criteria set has been quantitatively validated using patient data, and it has undergone validation based on an independent data set. All ACR/EULAR-approved criteria sets are expected to undergo intermittent updates.The ACR is an independent, professional, medical and scientific society that does not guarantee, warrant, or endorse any commercial product or service.This article is published simultaneously in Annals of the Rheumatic Diseases. The Diagnostic and Classification Criteria in Vasculitis (DCVAS) study, which included the development of this classification criteria, was funded by grants from the American College of Rheumatology (ACR), EULAR, the Vasculitis Foundation, and the
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