ABSTRACT
BACKGROUND: At present, clinical use of MRI in Alzheimer's disease (AD) is mostly focused on the assessment of brain atrophy, namely in the hippocampal region. Despite this, multiple biomarkers reflecting structural and functional brain connectivity changes have shown promising results in the assessment of AD. To help identify the most relevant ones that may stand a chance of being used in clinical practice, we compared multiple biomarker in terms of their value to discriminate AD from healthy controls and analyzed their age dependency. METHODS: 20 AD patients and 20 matched controls underwent MRI-scanning (3T GE), including T1-weighted, diffusion-MRI, and resting-state-fMRI (rsfMRI). Whole brain, white matter, gray matter, cortical gray matter and hippocampi volumes were measured using icobrain. rsfMRI between regions of the default-mode-network (DMN) was assessed using group independent-component-analysis. Median diffusivity and kurtosis were determined in gray and white-matter. DTI data was used to evaluate pairwise structural connectivity between lobar regions and the hippocampi.Logistic-Regression and Random-Forest models were trained to classify AD-status based on, respectively different isolated features and age, and feature-groups combined with age. RESULTS: Hippocampal features, features reflecting the functional connectivity between the medial-Pre-Frontal-Cortex (mPFC) and the posterior regions of the DMN, and structural interhemispheric frontal connectivity showed the strongest differences between AD-patients and controls. Structural interhemispheric parietal connectivity, structural connectivity between the parietal lobe and hippocampus in the right hemisphere, and mPFC-DMN-features, showed only an association with AD-status (p < 0.05) but not with age. Hippocampi volumes showed an association both with age and AD-status (p < 0.05).Smallest-hippocampus-volume was the most discriminative feature. The best performance (accuracy:0.74, sensitivity:0.74, specificity:0.74) was obtained with an RF-model combining the best feature from each feature-group (smallest hippocampus volume, WM volume, median GM MD, lTPJ-mPFC connectivity and structural interhemispheric frontal connectivity) and age. CONCLUSIONS: Brain connectivity changes caused by AD are reflected in multiple MRI-biomarkers. Decline in both the functional DMN-connectivity and the parietal interhemispheric structural connectivity may assist sepparating healthy-aging driven changes from AD, complementing hippocampal volumes which are affected by both aging and AD.
ABSTRACT
Ketamine and midazolam are commonly used in children undergoing cardiac catheterization. However, there is controversy regarding the safety of administering these agents in the absence of an anesthesiologist. We retrospectively reviewed pediatric cardiac catheterization procedures at our institution between 1996 and 1997. A total of 154 patients (0.3-192 months) underwent a total of 205 procedures. They received ketamine (n = 79, 1.05 +/- 0.88 mg/kg/hr), midazolam (n = 35, 0.14 +/- 0.09 mg/kg/hr), or both (n = 91; ketamine, 1.13 +/- 0.84 mg/kg/hr; midazolam, 1.57 +/- 1.03 mg/kg//hr). In 18.5% of patients there were complex cardiac lesions. Mean procedure time was 79 +/- 36.2 minutes. Pre- and postprocedure systolic and diastolic mean blood procedure 72 +/- 14 and 68 +/- 12 mmHg, respectively. Pre- and postprocedure O2 saturation was 93.19 +/- 8.72 and 93.63 +/- 8.3, respectively. One patient required intubation, and 15% required oxygen therapy. The mortality rate was zero. The anesthesiologist's assistance was requested by the cardiologist in 21 procedures (group A) and not requested in 184 procedures (group B). The two groups were not different in relation to the drug used (p = 0.283) or the complexity of the cardiac lesions (p = 0.051). However, there was significant difference between the two regarding the need for supporting drugs (3/21 vs 3/184, p = 0.02) or oxygen treatment (7/21 vs 26/184, p = 0.014). No patients in group B required intubation, whereas 14% and 1.6% required oxygen therapy and supporting drugs, respectively. We conclude that low-dose ketamine and midazolam can be administered safely to most pediatric patients by the cardiologist, who can safely predict the need for an anesthesiologist.
