Institution
Rush University Medical Center
Healthcare•Chicago, Illinois, United States•
About: Rush University Medical Center is a healthcare organization based out in Chicago, Illinois, United States. It is known for research contribution in the topics: Population & Dementia. The organization has 13915 authors who have published 29027 publications receiving 1379216 citations. The organization is also known as: Rush Presbyterian St. Luke's Medical Center.
Topics: Population, Dementia, Transplantation, Cognitive decline, Health care
Papers published on a yearly basis
Papers
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TL;DR: It is proposed that Aβ*56 may play a pathogenic role very early in the pathogenesis of Alzheimer's disease, as well as three amyloid-β oligomers previously described in mouse models, which are studied in several mouse models and systematically in humans.
Abstract: Alzheimer’s disease begins about two decades before the onset of symptoms or neuron death, and is believed to be caused by pathogenic amyloid-β aggregates that initiate a cascade of molecular events culminating in widespread neurodegeneration. The microtubule binding protein tau may mediate the effects of amyloid-β in this cascade. Amyloid plaques comprised of insoluble, fibrillar amyloid-β aggregates are the most characteristic feature of Alzheimer’s disease. However, the correspondence between the distribution of plaques and the pattern of neurodegeneration is tenuous. This discrepancy has stimulated the investigation of other amyloid-β aggregates, including soluble amyloid-β oligomers. Different soluble amyloid-β oligomers have been studied in several mouse models, but not systematically in humans. Here, we measured three amyloid-β oligomers previously described in mouse models—amyloid-β trimers, Aβ*56 and amyloid-β dimers—in brain tissue from 75 cognitively intact individuals, ranging from young children to the elderly, and 58 impaired subjects with mild cognitive impairment or probable Alzheimer’s disease. As in mouse models, where amyloid-β trimers appear to be the fundamental amyloid-β assembly unit of Aβ*56 and are present in young mice prior to memory decline, amyloid-β trimers in humans were present in children and adolescents; their levels rose gradually with age and were significantly above baseline in subjects in their 70s. Aβ*56 levels were negligible in children and young adults, rose significantly above baseline in subjects in their 40s and increased steadily thereafter. Amyloid-β dimers were undetectable until subjects were in their 60s; their levels then increased sharply and correlated with plaque load. Remarkably, in cognitively intact individuals we found strong positive correlations between Aβ*56 and two pathological forms of soluble tau (tau-CP13 and tau-Alz50), and negative correlations between Aβ*56 and two postsynaptic proteins (drebrin and fyn kinase), but none between amyloid-β dimers or amyloid-β trimers and tau or synaptic proteins. Comparing impaired with age-matched unimpaired subjects, we found the highest levels of amyloid-β dimers, but the lowest levels of Aβ*56 and amyloid-β trimers, in subjects with probable Alzheimer’s disease. In conclusion, in cognitively normal adults Aβ*56 increased ahead of amyloid-β dimers or amyloid-β trimers, and pathological tau proteins and postsynaptic proteins correlated with Aβ*56, but not amyloid-β dimers or amyloid-β trimers. We propose that Aβ*56 may play a pathogenic role very early in the pathogenesis of Alzheimer’s disease.
385 citations
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TL;DR: The selective dopamine-1 agonist fenoldopam mesylate does not prevent further renal function deterioration after contrast administration in patients with chronic renal insufficiency and is not effective in preventing contrast nephropathy.
Abstract: ContextThe development of contrast-induced nephropathy in patients undergoing
invasive cardiac procedures is associated with a marked increase in cardiovascular
morbidity and mortality. Fenoldopam mesylate, a specific agonist of the dopamine-1
receptor, preserves renal blood flow after iodinated contrast administration
and has shown promise in ameliorating contrast nephropathy in previous observational
and small randomized trials.ObjectiveTo examine the efficacy of fenoldopam mesylate in preventing contrast
nephropathy after invasive cardiovascular procedures.DesignProspective, placebo-controlled, double-blind, multicenter randomized
trial with serial serum creatinine levels measured at a central biochemistry
laboratory (at baseline and 1, 24, 48, and 72 to 96 hours after study drug
administration) and 30-day clinical follow-up.Patients and SettingBetween March 2001 and July 2002, 315 patients with creatinine clearance
less than 60 mL/min (1.00 mL/s) at 28 centers in the United States were randomized
to receive fenoldopam mesylate (n = 157) or placebo (n = 158).InterventionsPatients were hydrated and randomized to receive intravenous fenoldopam
(0.05 µg/kg/min titrated to 0.10 µg/kg/min) vs matching placebo,
starting 1 hour prior to angiography and continuing for 12 hours.Main Outcome MeasureContrast-induced nephropathy, defined as an increase of 25% or more
in serum creatinine level within 96 hours postprocedure.ResultsMean (SD) patient age was 70 (11) years, and 49% had diabetes mellitus.
Mean (SD) baseline creatinine clearance was 29.0 (10.0) mL/min (0.48 [0.16]
mL/s) (range, 7.5-56.8 mL/min [0.12-0.94 mL/s]), and 157 (108) mL of contrast
was administered during the procedures. The primary end point of contrast-induced
nephropathy occurred in 33.6% of patients assigned to receive fenoldopam vs
30.1% assigned to receive placebo (relative risk, 1.11; 95% confidence interval,
0.79-1.57; P = .61). There were no significant differences
in the 30-day rates of death (2.0% vs 3.8%, P = .50),
dialysis (2.6% vs 1.9%, P = .72), or rehospitalization
(17.6% vs 19.9%, P = .66) in fenoldopam vs placebo
randomized patients, respectively.ConclusionThe selective dopamine-1 agonist fenoldopam mesylate does not prevent
further renal function deterioration after contrast administration in patients
with chronic renal insufficiency.
384 citations
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TL;DR: Standardised neuropathological assessment criteria and the development of non-invasive means of detection during life would be major steps towards understanding the causes and consequences of otherwise macroscopically invisible microinfarcts.
Abstract: Summary The association between small but still visible lacunar infarcts and cognitive decline has been established by population-based radiological and pathological studies. Microscopic examination of brain sections shows even smaller but substantially more numerous microinfarcts, the focus of this Review. These lesions often result from small vessel pathologies such as arteriolosclerosis or cerebral amyloid angiopathy. They typically go undetected in clinical–radiological correlation studies that rely on conventional structural MRI, although the largest acute microinfarcts can be detected by diffusion-weighted imaging. In view of their high numbers and widespread distribution, microinfarcts could directly disrupt important cognitive networks and thus account for some of the neurological dysfunction associated with lesions visible on conventional MRI such as lacunar infarcts and white matter hyperintensities. Standardised neuropathological assessment criteria and the development of non-invasive means of detection during life would be major steps towards understanding the causes and consequences of otherwise macroscopically invisible microinfarcts.
383 citations
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TL;DR: Estimates of smoking's effects on cognitive decline may be underestimated due to differential attrition, especially for risk factors, such as smoking, that strongly influence mortality and dropout.
Abstract: Background
Selective attrition may introduce bias into analyses of the determinants of cognitive decline. This is a concern especially for risk factors, such as smoking, that strongly influence mortality and drop-out. Using inverse-probability-of-attrition weights (IPAWs), we examined the influence of selective attrition on the estimated association of current smoking (versus never smoking) with cognitive decline.
382 citations
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TL;DR: Clinical aspects of the disorder and new insights with respect to pathophysiology are reviewed, and potential new therapeutics based on the disease mechanism are discussed, such as prostacyclin analogues, serotonin antagonists, and calcitonin gene-related peptides.
382 citations
Authors
Showing all 14032 results
Name | H-index | Papers | Citations |
---|---|---|---|
John Q. Trojanowski | 226 | 1467 | 213948 |
Virginia M.-Y. Lee | 194 | 993 | 148820 |
Luigi Ferrucci | 193 | 1601 | 181199 |
David A. Bennett | 167 | 1142 | 109844 |
Todd R. Golub | 164 | 422 | 201457 |
David Cella | 156 | 1258 | 106402 |
M.-Marsel Mesulam | 150 | 558 | 90772 |
John D. E. Gabrieli | 142 | 480 | 68254 |
David J. Kupfer | 141 | 862 | 102498 |
Clifford B. Saper | 136 | 406 | 72203 |
Pasi A. Jänne | 136 | 685 | 89488 |
Nikhil C. Munshi | 134 | 906 | 67349 |
Martin B. Keller | 131 | 541 | 65069 |
Michael E. Thase | 131 | 923 | 75995 |
Steven R. Simon | 129 | 1090 | 80331 |