Annals of neurology
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Annals of neurology · Jun 2016
Pathological α-synuclein in gastrointestinal tissues from prodromal Parkinson disease patients.
It has been hypothesized that Lewy pathology initiates in the enteric nervous system years prior to debut of clinical motor symptoms in Parkinson disease patients. This study investigates whether Lewy pathology is present in various gastrointestinal tract tissues from Parkinson disease patients in the prodromal phase. ⋯ We detected Lewy pathology in the gastrointestinal tract of patients up to 20 years prior to their Parkinson disease diagnosis. These findings are in accordance with a hypothesized prodromal disease phase spanning 10 to 20 years. Ann Neurol 2016;79:940-949.
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Annals of neurology · Jun 2017
Multicenter StudyPyrimethamine significantly lowers cerebrospinal fluid Cu/Zn superoxide dismutase in amyotrophic lateral sclerosis patients with SOD1 mutations.
Cu/Zn superoxide dismutase (SOD1) reduction prolongs survival in SOD1-transgenic animal models. Pyrimethamine produces dose-dependent SOD1 reduction in cell culture systems. A previous phase 1 trial showed pyrimethamine lowers SOD1 levels in leukocytes in patients with SOD1 mutations. This study investigated whether pyrimethamine lowered SOD1 levels in the cerebrospinal fluid (CSF) in patients carrying SOD1 mutations linked to familial amyotrophic lateral sclerosis (fALS/SOD1). ⋯ Pyrimethamine is safe and well tolerated in ALS. Pyrimethamine is capable of producing a significant reduction in total CSF SOD1 protein content in patients with ALS caused by different SOD1 mutations. Further long-term studies are warranted to assess clinical efficacy. Ann Neurol 2017;81:837-848.
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Annals of neurology · Jan 2016
Tau positron emission tomographic imaging in aging and early Alzheimer disease.
Detection of focal brain tau deposition during life could greatly facilitate accurate diagnosis of Alzheimer disease (AD), staging and monitoring of disease progression, and development of disease-modifying therapies. ⋯ These findings suggest that (18)F T807 PET could have value as a biomarker that reflects both the progression of AD tauopathy and the emergence of clinical impairment.
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Annals of neurology · May 2005
ReviewNeurocognitive complications after coronary artery bypass surgery.
Both short- and long-term cognitive changes continue to occur after coronary artery bypass grafting (CABG), but the pathophysiology of these neurobehavioral changes remains incompletely understood. The persistence of mild postoperative neurocognitive changes despite multiple improvements in the cardiopulmonary bypass procedure may be partially because of surgical populations being older and having more prevalent comorbid disease. The cause of the early postoperative changes is most likely multifactorial and may include ischemic injury from microemboli, hypoperfusion, and other factors resulting from major surgery. ⋯ A history of hypertension and other risk factors for vascular disease is known to be associated with increased risk for long-term cognitive decline in community-dwelling elderly individuals. Cerebrovascular risk factors are also associated with silent magnetic resonance imaging abnormalities in patients undergoing CABG. Thus, whereas both short- and long-term postoperative cognitive changes have been associated with CABG, only the short-term, transient changes appear to be directly related to the use of cardiopulmonary bypass.
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Annals of neurology · Nov 2016
Specifically neuropathic Gaucher's mutations accelerate cognitive decline in Parkinson's.
We hypothesized that specific mutations in the β-glucocerebrosidase gene (GBA) causing neuropathic Gaucher's disease (GD) in homozygotes lead to aggressive cognitive decline in heterozygous Parkinson's disease (PD) patients, whereas non-neuropathic GD mutations confer intermediate progression rates. ⋯ Mutations in the GBA gene pathogenic for neuropathic GD and complex alleles shift longitudinal cognitive decline in PD into "high gear." These findings suggest a relationship between specific types of GBA mutations and aggressive cognitive decline and have direct implications for improving the design of clinical trials. Ann Neurol 2016;80:674-685.