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BACKGROUND Many recent studies have identified white matter abnormalities in late life depression (LLD). These abnormalities include an increased volume of discrete white matter hyperintensities on T2-weighted imaging (WMH) and changes in the diffusion tensor properties of water. However, no study of LLD to date has examined the integrity of white matter(More)
Identifying high-risk populations is an important component of disease prevention strategies. One approach for identifying at-risk populations for Alzheimer's disease (AD) is examining neuroimaging parameters that differ between patients, including functional connections known to be disrupted within the default-mode network. We have previously shown these(More)
BACKGROUND Disease-modifying therapies for Alzheimer's disease (AD) would be most effective during the preclinical stage (pathology present, cognition intact) before significant neuronal loss occurs. Therefore, biomarkers that detect AD pathology in its early stages and predict dementia onset and progression will be invaluable for patient care and efficient(More)
OBJECTIVE There is a growing need to identify cerebrospinal fluid (CSF) markers that can detect Alzheimer's disease (AD) pathology in cognitively normal individuals because it is in this population that disease-modifying therapies may have the greatest chance of success. While AD pathology is estimated to begin ~10-15 years prior to the onset of cognitive(More)
Aggregation of amyloid-β (Aβ) as toxic oligomers and amyloid plaques within the brain appears to be the pathogenic event that initiates Alzheimer's disease (AD) lesions. One therapeutic strategy has been to reduce Aβ levels to limit its accumulation. Activation of certain neurotransmitter receptors can regulate Aβ metabolism. We assessed the ability of(More)
In vivo quantification of β-amyloid deposition using positron emission tomography is emerging as an important procedure for the early diagnosis of the Alzheimer's disease and is likely to play an important role in upcoming clinical trials of disease modifying agents. However, many groups use manually defined regions, which are non-standard across imaging(More)
CONTEXT Research on vascular depression has used 2 approaches to subtype late-life depression, based on executive dysfunction or white matter hyperintensity severity. OBJECTIVE To evaluate the relationship of neuropsychological performance and white matter hyperintensity with clinical response in late-life depression. DESIGN Two-site, prospective,(More)
OBJECTIVE To evaluate the cognitive reserve hypothesis by examining whether individuals of greater educational attainment have better cognitive function than individuals with less education in the presence of elevated fibrillar brain amyloid levels. DESIGN, SETTING, AND PARTICIPANTS Uptake of carbon 11-labeled Pittsburgh Compound B ([(11)C]PiB) was(More)
Data are limited on the attributable outcomes of Clostridium difficile-associated disease (CDAD), particularly in CDAD-endemic settings. We conducted a retrospective cohort study of nonsurgical inpatients admitted for >/=48 hours in 2003 (N = 18,050). The adjusted hazard ratios for readmission (hazard ratio 2.19, 95% confidence interval [CI] 1.87-2.55) and(More)
Variable selection in genome-wide association studies can be a daunting task and statistically challenging because there are more variables than subjects. We propose an approach that uses principal-component analysis (PCA) and least absolute shrinkage and selection operator (LASSO) to identify gene-gene interaction in genome-wide association studies. A PCA(More)