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Valid, applicable models with low risk of bias were found in two settings advanced dementia in a nursing home and outpatient practices. The outpatient model requires external validation. Better models are needed for persons with mild to moderate dementia in nursing homes, a common demographic. These models may be useful for educating persons living with dementia and care partners and directing resources for end of life care.RegistrationThe study protocol is registered on PROSPERO as RD4202018076. Valid, applicable models with low risk of bias were found in two settings advanced dementia in a nursing home and outpatient practices. The outpatient model requires external validation. Better models are needed for persons with mild to moderate dementia in nursing homes, a common demographic. These models may be useful for educating persons living with dementia and care partners and directing resources for end of life care.RegistrationThe study protocol is registered on PROSPERO as RD4202018076. Cerebral amyloid angiopathy with related inflammation (CAA-ri) is a rare age-associated disorder characterized by an inflammatory response to amyloid in cerebral blood vessels. CAA-ri is often treated with corticosteroids, but response to treatment is variable. To assess the relationship between clinical and paraclinical measures and outcomes in patients with CAA-ri treated with high doses of methylprednisolone. Longitudinal clinical course, and results from serum and cerebrospinal fluid (CSF) testing, electroencephalography, and neuroimaging were reviewed from 11 prospectively-accrued CAA-ri patients diagnosed, treated, and followed at Barnes Jewish Hospital (St. Louis, MO, USA). Magnetic resonance imaging (MRI) changes were quantified using a scoring system validated in cases of amyloid related imaging abnormality (ARIA-E). Clinical outcomes were assessed as change in modified Rankin Scale (ΔmRS) from baseline to final assessment (median 175 days from treatment with high doses of methylprednisolone; range, 31-513). Worse outcomes following methylprednisolone treatment were associated with requirement for intensive care unit admission (median ΔmRS, 5 versus 1.5; p = 0.048), CSF pleocytosis (median ΔmRS 4.5 versus 1; p = 0.04), or lower CSF Aβ40 at presentation (rho = -0.83; p = 0.02), and diffusion restriction (median ΔmRS 4 versus 1.5; p = 0.03) or higher late ARIA-E scores (rho = 0.70; p = 0.02) on MRI, but not preexisting cognitive decline (median ΔmRS 2 versus 2; p = 0.66). Clinical and paraclinical measures associated with outcomes may inform clinical counseling and treatment decisions in patients with CAA-ri. Baseline cognitive status was not associated with treatment responsiveness. Clinical and paraclinical measures associated with outcomes may inform clinical counseling and treatment decisions in patients with CAA-ri. Baseline cognitive status was not associated with treatment responsiveness. The apolipoprotein E (APOE) ɛ4 allele is associated with dose-response effects on cognitive dysfunction and dementia risk in older adults. However, its effects on cognition in middle-aged adults remains unclear. We examined effects of ɛ4 heterozygosity and homozygosity on objective and subjective cognition in middle-aged adults enrolled in the Healthy Brain Project (HBP) and in older adults from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. HBP participants (1,000 non-carriers; 450 ɛ4 heterozygotes; 50 ɛ4 homozygotes) completed unsupervised assessments of the Cogstate Brief Battery (CBB), ratings of subjective cognitive function and provided a saliva sample. AIBL cognitively normal participants (650 non-carriers; 204 ɛ4 heterozygotes; 31 ɛ4 homozygotes) completed in-person assessments of the CBB, ratings of subjective cognitive function and provided a blood sample. Greater memory impairment was observed in middle-aged ɛ4 homozygotes compared with ɛ4 heterozygotes and non-carriers. Whe our findings support the necessity of online platforms in large cohorts to assess these complex relationships. There is a need for more reliable diagnostic tools for the early detection of Alzheimer's disease (AD). This can be a challenge due to a number of factors and logistics making machine learning a viable option. In this paper, we present on a Support Vector Machine Leave-One-Out Recursive Feature Elimination and Cross Validation (SVM-RFE-LOO) algorithm for use in the early detection of AD and show how the SVM-RFE-LOO method can be used for both classification and prediction of AD. Data were analyzed on n = 300 participants (n = 150 AD; n = 150 cognitively normal controls). Serum samples were assayed via a multi-plex biomarker assay platform using electrochemiluminescence (ECL). The SVM-RFE-LOO method reduced the number of features in the model from 21 to 16 biomarkers and achieved an area under the curve (AUC) of 0.980 with a sensitivity of 94.0% and a specificity of 93.3%. When the classification and prediction performance of SVM-RFE-LOO was compared to that of SVM and SVM-RFE, we found similar performance across the models; however, the SVM-RFE-LOO method utilized fewer markers. We found that 1) the SVM-RFE-LOO is suitable for analyzing noisy high-throughput proteomic data, 2) it outperforms SVM-RFE in the robustness to noise and in the ability to recover informative features, and 3) it can improve the prediction performance. Our recursive feature elimination model can serve as a general model for biomarker discovery in other diseases. We found that 1) the SVM-RFE-LOO is suitable for analyzing noisy high-throughput proteomic data, 2) it outperforms SVM-RFE in the robustness to noise and in the ability to recover informative features, and 3) it can improve the prediction performance. Our recursive feature elimination model can serve as a general model for biomarker discovery in other diseases. The overlap between cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD) is frequent and relevant for patients with cognitive impairment. To assess the role of the diagnosis of CAA on the phenotype of amyloid-β (Aβ) positive patients from a university-hospital memory clinic. Consecutive patients referred for suspected cognitive impairment, screened for Aβ pathological changes in cerebrospinal fluid (CSF), with available MRI and neuropsychological results were included. https://www.selleckchem.com/products/AZD0530.html We determined the association between probable CAA and clinical, neuropsychological (at presentation and after a mean follow-up of 17 months in a sub-sample) and MRI (atrophy, white matter hyperintensities, perivascular spaces) characteristics. Of 218 amyloid-positive patients, 8.3% fulfilled criteria for probable CAA. A multivariable logistic regression showed an independent association of probable CAA with lower Aβ1-42 (adjusted odds ratio [aOR] = 0.94, 95% confidence interval [95% CI] = 0.90-0.98, p = 0.003), and Aβ1-40 (aOR = 0.
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