There are many active research projects accessing and applying shared ADNI data. Use the search above to find specific research focuses on the active ADNI investigations. This information is requested annually as a requirement for data access.
| Principal Investigator | |
| Principal Investigator's Name: | Jodi Edwards |
| Institution: | University of Ottawa Heart Institute |
| Department: | Epidemiology |
| Country: | |
| Proposed Analysis: | Comparing the diagnostic accuracy of inflammatory markers of blood brain barrier permeability for dementia classification Background and rationale: Atrial fibrillation (AF) is one of the most prevalent forms of cardiac arrhythmia. AF is characterized by abnormal atrial depolarisations with a discrete lack of P waves on electrocardiograms.1 Due to this irregularity in blood flow, the blood in the heart has an increased chance of forming a blood clot, making AF one of the leading cardiac causes of stroke. There is growing evidence that AF is a risk factor for cognitive decline, such as dementia. A potential mechanism of the rapid cognitive decline and increased dementia risk among individuals with AF that has not been explored extensively is potential dysfunction of blood-brain barrier (BBB). The BBB plays a vital role in maintaining boundaries between the central nervous system and the periphery circulation by regulating the passage of nutrients and waste in the bloodstream and protecting neurons from toxins. Compromising the integrity of the BBB may affect the development of the brain vasculature and increase the risk for dementia. A number of studies have shown that systematic inflammation in the BBB accelerates the course of cognitive decline, and several blood-based markers of systematic inflammation, such as C-reactive protein (CRP), Interleukin-6 (IL-6), and Fibrinogen (Fg) have been shown to be associated with BBB integrity.2 However, it is currently unknown which of these blood-based markers demonstrate the highest sensitivity and specificity for predicting dementia. Purpose and specific objectives: The purpose of this project is to compare the burden and diagnostic accuracy of three blood-based inflammatory markers: C-reactive protein (CRP), Interleukin-6 (IL-6), and Fibrinogen (Fg) in aging dults with and without atrial fibrillation (AF) to investigate the potential relationship between BBB dysfunction, AF and dementia. Materials and methods: Data for this study will be obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort (www.adni.ca). All individuals with baseline measures of CRP, IL-6 and Fg will be identified and we will exclude those with prevalent dementia at baseline. The burden of each of these blood-based markers will be compared in elderly adults with and without AF and diagnostic accuracy tested using a receiver operating characteristic-area (ROC-AUC) under the curve analysis using R. ROC curve is a statistical tool that characterizes how accurately a diagnostic test can discriminate between a subject with and without a particular condition by plotting a diagnostic test’s true positive rate ( = specificity) on the y-axis and its false negative rate ( = 1 - specificity) on the x-axis.3 Sensitivity refers to the proportion of subjects who have the condition of interest and yield positive results (= true positives/[true positives + false negatives]). Specificity refers to the proportion of subjects who do not have the condition of interest and yield negative results (= true negatives/[true negatives + false positives]).4 A perfect diagnostic test would have a sensitivity and specificity of 100%.5 The area under the ROC curve (AUC) can numerically quantify the accuracy of the diagnostic test. A test that perfect discriminates between the presence or absence of the condition of interest will have an AUC of 1.0. Expected results: By doing this project, we expect to identify the most sensitive blood-based inflammatory marker to further investigate the role of the BBB in the relationship between vasuclar aging, AF and dementia. |
| Additional Investigators |
