Biochemical, neuropathological, and neuroimaging characteristics of early-onset Alzheimer's disease due to a novel PSEN1 mutation.

Familial Alzheimer's disease (AD) due to PSEN1 mutations provides an opportunity to examine AD biomarkers in persons in whom the diagnosis is certain. We describe a 55 year-old woman with clinically probable AD and a novel PSEN1 mutation who underwent genetic, clinical, biochemical and magnetic resonance and nuclear imaging assessments. We also describe neuropathological findings in her similarly affected brother.

Defining optimal treatment with cholinesterase inhibitors in Alzheimer's disease.

Despite growing recognition that Alzheimer's disease (AD) represents a global public health and social care crisis, diagnosis is frequently slow and many patients still receive no treatment at all. Of those who do receive treatment, many remain on lower than recommended doses. The Alzheimer's disease International Global Charter promotes awareness and understanding of AD, stressing the importance of optimal treatment.

Wavelet analysis used for spectral background removal in the determination of glucose from near-infrared single-beam spectra.

Wavelet analysis is developed as a preprocessing tool for use in removing background information from near-infrared (near-IR) single-beam spectra before the construction of multivariate calibration models. Three data sets collected with three different near-IR spectrometers are investigated that involve the determination of physiological levels of glucose (1-30 mM) in a simulated biological matrix containing alanine, ascorbate, lactate, triacetin, and urea in phosphate buffer. A factorial design is employed to optimize the specific wavelet function used and the level of decomposition applied, in addition to the spectral range and number of latent variables associated with a partial least-squares calibration model.

Synthetic training sets for the development of discriminant functions for the detection of volatile organic compounds from passive infrared remote sensing data.

A novel synthetic data generation methodology is described for use in the development of pattern recognition classifiers that are employed for the automated detection of volatile organic compounds (VOCs) during infrared remote sensing measurements. The approach used is passive Fourier transform infrared spectrometry implemented in a downward-looking mode on an aircraft platform. A key issue in developing this methodology in practice is the need for example data that can be used to train the classifiers.

Assessment of processed porcine extracellular matrix as a protective barrier in a rabbit nerve wrap model.

Nerve wrapping can improve outcomes by protecting nerves in a scarred tissue bed. Autologous tissue wraps have shown good results, but there are limitations associated with harvesting and availability. Extracellular matrix (ECM) derived from porcine small intestinal submucosa offers an attractive off-the-shelf option.

Family history of Alzheimer's disease and hippocampal structure in healthy people.

Objective: Structural brain changes appear years before the onset of Alzheimer's disease, the leading cause of dementia late in life. Determining risk factors for such presymptomatic brain changes may assist in identifying candidates for future prevention treatment trials. In addition to the e4 allele of the apolipoprotein E gene (APOE-4), the major known genetic risk factor, a family history of Alzheimer's disease also increases the risk to develop the disease, reflecting yet unidentified genetic and, perhaps, nongenetic risks.

Isolated laryngeal myokymia: diagnosis and treatment.

Myokymia is an uncommon neuromuscular disorder that rarely affects the human larynx. No previous reports of isolated laryngeal myokymia are present in the literature, and as such, established treatment protocols are lacking. We report the first case of isolated laryngeal myokymia in a 48-year-old woman with no other neurological findings, and our successful results in initial treatment and maintenance therapy with focal intralaryngeal injections of botulinum toxin A.

Longitudinal changes in medial temporal cortical thickness in normal subjects with the APOE-4 polymorphism.

People with the apolipoprotein-Eepsilon4 (APOE-4) genetic risk for Alzheimer's disease show morphologic differences in medial temporal lobe regions when compared to non-carriers of the allele. Using a high-resolution MRI and cortical unfolding approach, our aim was to determine the rate of cortical thinning among medial temporal lobe subregions over the course of 2 years. We hypothesized that APOE-4 genetic risk would contribute to longitudinal cortical thickness change in the subiculum and entorhinal cortex, regions preferentially susceptible to Alzheimer's disease related pathology.

Improved heart function follows enhanced inflammatory cell recruitment and angiogenesis in 11betaHSD1-deficient mice post-MI.

Aims: Mice unable to locally regenerate corticosterone due to deficiency of 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) have enhanced angiogenesis during acute myocardial infarct healing. The present study investigates the hypotheses that in these mice (i) inflammation and angiogenic signalling are promoted and (ii) longer-term remodelling and function are improved.

Methods And Results: Myocardial infarction (MI) was induced by coronary artery ligation in 11βHSD1(-/-) and wild-type (C57BL/6) mice.

Therapeutics for cognitive aging.

This review summarizes the scientific talks presented at the conference "Therapeutics for Cognitive Aging," hosted by the New York Academy of Sciences and the Alzheimer's Drug Discovery Foundation on May 15, 2009. Attended by scientists from industry and academia, as well as by a number of lay people-approximately 200 in all-the conference specifically tackled the many aspects of developing therapeutic interventions for cognitive impairment. Discussion also focused on how to define cognitive aging and whether it should be considered a treatable, tractable disease.

Specific estrogen sulfotransferase (SULT1E1) substrates and molecular imaging probe candidates.

This work focuses on the development of specific substrates for estrogen sulfotransferase (SULT1E1) to produce molecular imaging probes for this enzyme. SULT1E1 is a key enzyme in estrogen homeostasis, playing a central role in the prevention and development of human disease. In vitro sulfation assays showed alkyl and aryl substitutions to a fused heterocyclic system modeled after beta-naphthol (betaN), based on compounds that interact with the estrogen receptor, rendered several molecules with enhanced specificity for SULT1E1 over SULT1A1*1, SULT1A1*2, SULT1A3, and SULT2A1.

Pharmacotherapy and other treatments for elderly patients with depression.

Depression in older adults can be difficult to diagnose and a challenge to treat. Clinicians must address treatment issues caused by aging, such as comorbid medical illness, physical limitations, or the presence of cognitive impairments. Proven treatments for depression in older adults include psychotherapy, medications, and electroconvulsive therapy.

Noninvasive assessment of left ventricular filling pressure after acute myocardial infarction: a prospective study of the relative prognostic utility of clinical assessment, echocardiography, and B-type natriuretic peptide.

Background: Elevated left ventricular filling pressure after acute myocardial infarction (AMI) may be identified using clinical assessment, echocardiography, and B-type natriuretic peptide (BNP) levels. All of these predict outcome in this setting. There are, however, no data assessing their relative prognostic value.

Movement correction method for human brain PET images: application to quantitative analysis of dynamic 18F-FDDNP scans.

Unlabelled: Head movement during a PET scan (especially a dynamic scan) can affect both the qualitative and the quantitative aspects of an image, making it difficult to accurately interpret the results. The primary objective of this study was to develop a retrospective image-based movement correction (MC) method and evaluate its implementation on dynamic 2-(1-{6-[(2-(18)F-fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ((18)F-FDDNP) PET images of cognitively intact controls and patients with Alzheimer's disease (AD).

Methods: Dynamic (18)F-FDDNP PET images, used for in vivo imaging of beta-amyloid plaques and neurofibrillary tangles, were obtained from 12 AD patients and 9 age-matched controls.

Reduced hippocampal CA2, CA3, and dentate gyrus activity in asymptomatic people at genetic risk for Alzheimer's disease.

Previous functional magnetic resonance imaging (MRI) studies in healthy subjects with the apolipoprotein Eepsilon4 (APOE-4) genetic risk for Alzheimer's disease have shown increased activation during memory task performance in broadly distributed cortical regions. These findings have been hypothesized to reflect compensatory recruitment of intact brain regions that presumably result from subtle neural dysfunction reflecting incipient disease. In this study, we used high-resolution functional MRI in APOE-4 carriers and non-carriers to measure activity in hippocampal subregions (CA fields 1, 2, 3; dentate gyrus [DG], and subiculum) and adjacent medial temporal lobe (parahippocampal and entorhinal) subregions.

Deviation from strict homeostasis across multiple trophic levels in an invertebrate consumer assemblage exposed to high chronic phosphorus enrichment in a Neotropical stream.

A central tenet of ecological stoichiometry is that consumer elemental composition is relatively independent of food resource nutrient content. Although the P content of some invertebrate consumer taxa can increase as a consequence of P-enriched food resources, little is known about how ecosystem nutrient loading can affect the elemental composition of entire consumer assemblages. Here we examine the potential for P enrichment across invertebrate consumer assemblages in response to chronic high P loading.

Quantitative analysis of [18F]FDDNP PET using subcortical white matter as reference region.

Purpose: Subcortical white matter is known to be relatively unaffected by amyloid deposition in Alzheimer's disease (AD). We investigated the use of subcortical white matter as a reference region to quantify [(18)F]FDDNP binding in the human brain.

Methods: Dynamic [(18)F]FDDNP PET studies were performed on 7 control subjects and 12 AD patients.

Oleate beta-oxidation in yeast involves thioesterase but not Yor180c protein that is not a dienoyl-CoA isomerase.

The beta-oxidation of oleic acid in Saccharomyces cerevisiae (S. cerevisiae) was studied by comparing the growth of wild-type cells on oleic acid or palmitic acid with the growth of mutants that either had a deletion in the YOR180c (DCI1) gene reported to encode delta3,5,delta2,4-dienoyl-CoA isomerase (dienoyl-CoA isomerase) or in the PTE1 gene encoding peroxisomal thioesterase 1. Growth of wild-type cells was indistinguishable from that of YOR180c mutant cells on either palmitic acid or oleic acid, whereas the PTE1 mutant grew slower and to a lower density on oleic acid but not on palmitic acid.

Utility of intraoperative electromyography in microvascular decompression for hemifacial spasm: a meta-analysis.

Object: In this paper, the authors' goal was to determine the utility of monitoring the abnormal muscle response (AMR) or "lateral spread" during microvascular decompression surgery for hemifacial spasm.

Methods: The authors' experience with AMR as well as the data available in the English-language literature regarding resolution or persistence of AMR and the resolution or persistence of hemifacial spasm at follow-up was pooled and subjected to a meta-analysis.

Results: The pooled OR revealed by the meta-analysis was 4.

PET of brain prion protein amyloid in Gerstmann-Sträussler-Scheinker disease.

In vivo amyloid PET imaging was carried out on six symptomatic and asymptomatic carriers of PRNP mutations associated with the Gerstmann-Sträussler-Scheinker (GSS) disease, a rare familial neurodegenerative brain disorder demonstrating prion amyloid neuropathology, using 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([F-18]FDDNP). 2-Deoxy-2-[F-18]fluoro-d-glucose PET ([F-18]FDG) and magnetic resonance imaging (MRI) scans were also performed in each subject. Increased [F-18]FDDNP binding was detectable in cerebellum, neocortex and subcortical areas of all symptomatic gene carriers in close association with the experienced clinical symptoms.