To investigate whether longitudinal declines in cognition are associated with higher fibrillar amyloid-beta (Abeta) deposition in vivo in individuals without dementia.
(11)CPiB images were obtained ...to measure fibrillar Abeta burden in 57 participants without dementia from the Baltimore Longitudinal Study of Aging. Participants (33 men, 24 women) had a mean (SD) age of 78.7 (6.2) years. Six participants (4 men, 2 women) had mild cognitive impairment defined as Clinical Dementia Rating = 0.5. To measure (11)CPiB retention, distribution volume ratios (DVR) for 15 regions of interest were estimated by fitting a simplified reference tissue model to the measured time activity curves. Mixed effects regression was used to predict cognitive trajectories over time using data before and including time of PiB (mean follow-up 10.8 years), with mean cortical DVR, age at baseline, sex, and education as independent predictors. Voxel-based analysis identified local associations.
(11)CPiB retention was higher in older individuals. Greater declines over time in mental status and verbal learning and memory, but not visual memory, were associated significantly with higher PiB retention. Voxel-based analysis showed significant associations in frontal and lateral temporal regions.
Higher Abeta deposition is associated with greater longitudinal decline in mental status and verbal memory in the preceding years. The differential association for verbal but not visual memory may reflect the greater reliance of verbal word list learning on prefrontal regions, which show early Abeta deposition. Prospective imaging may help distinguish between individuals with evolving neuropathology who develop accelerated cognitive decline vs those with normal aging.
PET imaging agents such as Pittsburgh compound B (PiB) allow detection of fibrillar β-amyloid (Aβ) in vivo. In addition to quantification of Aβ deposition in mild cognitive impairment and Alzheimer's ...disease, PiB has also increased our understanding of Aβ deposition in older adults without cognitive impairment. In vivo Aβ deposition has been studied in relation to genotype, structural and functional brain changes, as well as alterations in biomarker levels. To date, several studies have reported changes in Aβ burden over time. This, together with investigation of the relationship between Aβ deposition and cognition, sets the stage for elucidation of the temporal sequence of the neurobiological events leading to cognitive decline. Furthermore, correlation of Aβ levels detected by PiB PET and those obtained from biopsy or postmortem specimens will allow more rigorous quantitative interpretation of PiB PET data in relation to neuropathological evaluation. Since the first human study in 2004, in vivo amyloid imaging has led to advances in our understanding of the role of Aβ deposition in human aging and cognitive decline, as well as provided new tools for patient selection and therapeutic monitoring in clinical trials.
Anemia has been associated with elevated cerebral blood flow (CBF) in animal models and certain clinical conditions (eg, renal disease), but whether hemoglobin level variations across a relatively ...normal range are associated with local or diffuse CBF changes is unclear. We investigated whether lower hemoglobin is associated with regional increases in relative CBF in older individuals, and if these increases occur in watershed regions.
Seventy-four older nondemented adults underwent serial (15)O water positron emission tomography scans. Voxel-based analysis was used to investigate regional relative CBF patterns in association with hemoglobin level and in individuals with and without anemia. Analyses of cross-sectional relations between regional CBF and anemia were performed separately at two time points, 2 years apart, to identify replicable patterns of associations.
Restricting results to associations replicated across two cross-sectional analyses, lower hemoglobin was associated with higher relative CBF within the middle/inferior frontal, occipital, precuneus, and cerebellar regions. In addition, individuals with anemia (n = 15) showed higher relative CBF in superior frontal, middle temporal, hippocampal, and gyrus rectus regions than those without anemia. In some regions (right superior temporal gyrus, left inferior frontal gyrus, midline cuneus, and right precuneus); however, lower hemoglobin was associated with lower relative CBF.
In nondemented individuals, lower hemoglobin is associated with elevated relative CBF in specific cortical areas but reduced CBF in other areas. Whether this association between anemia and CBF in the absence of chronic diseases and in a normal physiologic range is related to clinical endpoints warrants further study.
Ictal brain SPECT (IS) findings in neocortical epilepsy (patients without mesiotemporal sclerosis) can be subtle. This study is aimed at assessing how the seizure focus identification was improved by ...the inclusion of individual IS and interictal brain SPECT (ITS)-MRI image registration as well as performing IS - ITS image subtraction.
The study involved the posthoc analysis of 64 IS scans using 99mTc-ethyl cysteinate dimer that were obtained in 38 patients without mesiotemporal sclerosis but with or without other abnormalities on MRI. Radiotracer injection occurred during video-electroencephalographic (EEG) monitoring. Patients were injected 2-80 s (median time, 13 s) after clinical or EEG seizure onset. All patients had sufficient follow-up to correlate findings with the SPECT results. All patients had ITS and MRI, including a coronal volume sequence used for registration. Image registration (IS and ITS to MRI) was performed using automated software. After normalization, IS - ITS subtraction was performed. The IS, ITS, and subtraction studies were read by 2 experienced observers who were unaware of the clinical data and who assessed the presence and localization of an identifiable seizure focus before and after image registration and subtraction. Correlation was made with video-EEG (surface and invasive) and clinical and surgical follow-up.
Probable or definite foci were identified in 38 (59%) studies in 33 (87%) patients. In 52% of the studies, the image registration aided localization, and in 58% the subtraction images contributed additional information. In 9%, the subtraction images confused the interpretation. In follow-up after surgery, intracranial EEG or video-EEG monitoring (or both) has confirmed close or reasonable localization in 28 (74%) patients. In 6 (16%) patients, SPECT indicated false seizure localization.
Image registration and image subtraction improve the localization of neocortical seizure foci using IS, but close correlation with the original images is required. False localizations occur in a minority of patients.
The Framingham Heart Study group cardiovascular disease risk profile (FCRP) score was used to assess the relationship between baseline cardiovascular risk and subsequent changes in resting state ...cerebral blood flow (CBF) in cognitively normal older participants from the Baltimore Longitudinal Study of Aging.
Ninty-seven cognitively normal participants underwent annual resting-state positron emission tomography scans at baseline and over a period of up to 8 years (mean interval, 7.4 years). Images quantifying voxel-wise longitudinal rates of CBF change were calculated and used to examine the relationship between baseline FCRP score and changes over time in regional CBF. Individual components of the FCRP score (age, cholesterol, blood pressure, smoking status, and type 2 diabetes) were also correlated with changes in regional CBF to examine the independent contributions of each component to the overall pattern of change.
Higher baseline FCRP scores were associated with accelerated longitudinal decline in CBF in orbitofrontal, medial frontal/anterior cingulate, insular, precuneus, and brain stem regions. Of the components that comprise the FCRP score, higher diastolic blood pressure and diabetes were associated independently with greater decline in the medial frontal/anterior cingulate and insular regions, respectively.
Baseline cardiovascular risk factors are associated with greater rates of decline in resting state regional brain function. The regions showing accelerated decline participate in higher-order cognitive processes and are also vulnerable to age-related neuropathology. These results, in conjunction with other studies, encourage early treatment of cardiovascular risk factors in older individuals.
We have studied in vitro alveolar macrophages (AMs) obtained by tracheobronchial lavage from rats exposed to subacute (3 hours and 3 days) and chronic (3 weeks) hypoxia (FiO2 = 0.1) and from rats ...recovering from chronic hypoxia. Hydrogen peroxide production by AMs was measured by luminol-dependent chemiluminescence after AMs adhered to the walls of the measuring cuvette, after stimulation with phorbol-myristate-acetate (PMA), and when N-formyl-methionyl-leucyl-phenylanine (FMLP) was added subsequently to the cells which had been previously stimulated by adherence or PMA. H2O2 production after cell adherence and adherence combined with FMLP stimulation did not differ between the groups. The increase of H2O2 production after adding PMA, and FMLP in addition to PMA was significantly higher in AMs from rats exposed to hypoxia for 3 days than in the controls. Other experimental groups did not differ from their controls. It is concluded that 3 days' hypoxia primes AMs for enhanced production of H2O2 upon stimulation. The mechanism is probably at the level of synthesis of proteins involved in H2O2 production, or the shift to a more reactive phenotype of alveolar macrophages subpopulations.
Production of hydrogen peroxide by rat lung alveolar macrophages represents one of the key events in the inflammatory process. For the interpretation of the in vitro measurements it is important to ...control all possible interfering influences. The present work documents that the type of anaesthesia might critically influence the observed results. H2O2 production was measured in isolated rat alveolar macrophages by luminol chemiluminescence catalyzed by horseradish peroxidase. Three different mechanisms of H2O2 production were observed after stimulation of cells with a chemotactic peptide (FMLP), phorbol ester (PMA), and during cell adherence. All these activities were influenced independently by the treatment with barbiturates, which both stimulated or inhibited the H2O2 production, depending on the barbiturate concentration. As the effective barbiturate concentrations were found to be within the range used for the anaesthesia of experimental animals, the presented results imply that barbiturates are not suitable for experiments in which the production of reactive oxygen species by phagocytes is measured, and that other anaesthetics should be tested.
Basal ganglia or thalamic activation has been reported in ictal SPECT studies of patients with intractable epilepsy. We hypothesized that lateralization of activation of these subcortical structures ...may aid in the lateralization of seizure foci in patients in whom the cortical focus is subtle or equivocal.
This was a retrospective analysis of 72 ictal (99m)Tc-ethylcysteinate dimer SPECT studies in 43 patients with intractable epilepsy in whom seizure laterality could be eventually determined. All patients underwent video-electroencephalography (EEG) monitoring, MRI, and one or more ictal SPECT scans as well as an interictal SPECT scan. Intracranial electrode EEG monitoring and surgery were performed as clinically indicated. Ictal and interictal studies were coregistered with patients' MRI scans using automated software, and ictal minus interictal subtraction images were obtained. The presence of asymmetric basal ganglia or thalamic activation was determined by 2 experienced observers who were unaware of clinical information. The final seizure focus was determined by surgical cure in 37 patients. In patients in whom surgery was not indicated or initial surgery was performed at another institution (n = 6), a consistent focus detected by intracranial electrode monitoring or repeated stereotypical seizures all originating from the same site on video-surface EEG monitoring was considered to indicate the final seizure focus.
Thirty-five patients had neocortical seizures and 8 had mesial temporal lobe seizures. Asymmetric basal ganglia activation was seen in 22 (30.6%) studies. This activation was ipsilateral to the final determined seizure focus in 17 of 22 of these studies (77.3%) and contralateral in 5 of 22 (21.7%). Asymmetric thalamic activation was seen in 15 studies (20.8%), of which 12 of 15 (80%) were ipsilateral to the final seizure focus, whereas 3 of 15 (20%) were contralateral. In 3 of 5 studies with contralateral basal ganglia activation and 1 of 3 studies with contralateral thalamic activation, the SPECT study as a whole was found to be falsely localizing. In another 2 cases of contralateral subcortical activation, the SPECT study as a whole was considered nonlocalizing. Worse outcome was not observed in patients with false ictal SPECT subcortical lateralization; however, the presence of asymmetric subcortical uptake, regardless of relationship to seizure focus, was associated with decreased incidence of seizures at 1 y after surgery.
Although asymmetric basal ganglia or thalamic activation is common, it is rarely the sole indicator of seizure localization. However, it may be a useful confirmatory sign in subtle cases of cortical localization. In cases of false ictal SPECT subcortical lateralization, the basal ganglia appear to follow cortical activation pattern. Furthermore, there appears to be a correlation between lateralizing uptake in subcortical structures on ictal SPECT and postsurgical outcome in intractable epilepsy patients.
•Nanocones were prepared by Metal Organic Vapour Phase Epitaxy.•Nanocones were fully covered by Ag nanoparticles deposited from aqueous solution of silver nitrate.•A part of nanocones under study was ...covered by thin layer of Molybdenum disulphide.
Zinc-doped gallium phosphide (GaP) nanowires and nanocones were grown by metal organic vapour phase epitaxy (MOVPE) on GaP〈1 1 1〉B substrates by a VLS technique using 30 nm colloidal gold particles as seeds. The growth was performed in an AIX 200 MOVPE low-pressure reactor between 500 and 690 °C. As the growth temperature Tg was increased, GaP nanocrystals changed their shape from rod-like nanowires at 500 °C through tapered nanocones at between 610 and 660 °C and finally to biconical shape at 690 °C. The nanocones had hexagonal cross-sections at their bases following the orientation of the substrate. GaP substrates were nanostructured with nanowires or nanocones with the aim to create experimental platforms for further exploration namely for (1) the deposition of Ag nanoballs that should facilitate surface enhanced Raman scattering, and (2) the synthesis of a thin molybdenum disulphide (MoS2) layer that would be suitable for solar cell and water disinfection applications.
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