Prolonged cholinergic enrichment influences regional cortical activation in early Alzheimer's disease

Neuroimaging studies of cholinesterase inhibitor (ChEI) treatment in Alzheimer's disease (AD) indicate that the short and long term actions of ChEIs are dissimilar. fMRI studies of the ChEI rivastigmine have focused on its short term action. In this exploratory study the effect of prolonged (20 weeks) rivastigmine treatment on regional brain activity was measured with fMRI in patients with mild AD. Eleven patients with probable AD and nine age-matched controls were assessed with a Pyramids and Palm Trees semantic association and an n-back working memory fMRI paradigm. In the patient group only, the assessment was repeated after 20 weeks of treatment. There was an increase in task-related brain activity after treatment with activations more like those of normal healthy elderly. Behaviorally, however, there were no significant differences between baseline and retest scores, with a range of performance probably reflecting variation in drug efficacy across patients. Variable patient response and drug dynamic/kinetic factors in small patient groups will inevitably bias (either way) the effect size of any relevant drug related changes in activation. Future studies should take drug response into account to provide more insight into the benefits of ChEI drugs at the individual level

Cognitive speed and white matter integrity in secondary progressive multiple sclerosis

BACKGROUND: Processing speed (PS) deficits have been consistently observed in secondary progressive multiple sclerosis (SPMS). However, the underlying neural correlates have not been clarified yet. The present study aimed to investigate the relationship between macrostructural and microstructural white matter (WM) integrity and performance on different cognitive measures with prominent PS load. METHODS: Thirty-one patients with SPMS were recruited and underwent neurological, neuropsychological, and MRI assessments. The associations between a composite index of PS abilities and scores on various tests with prominent PS load and T1-weighted and diffusion tensor image parameters were tested. Analyses were carried out using voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS). RESULTS: VBM results showed that only the semantic fluency task correlated with grey matter (GM) volume in a range of cortical and subcortical areas bilaterally as well as the corpus callosum and the superior longitudinal fasciculus. TBSS analysis revealed consistent results across all the cognitive measures investigated, showing a prominent role of commissural and frontal associative WM tracts in supporting PS-demanding cognitive operations. CONCLUSIONS: In patients with SPMS, PS abilities are mainly dependent on the degree of both macrostructural and microstructural WM integrity. Preservation of associative WM tracts that support information integration seems crucial to sustain performance in tasks requiring fast cognitive processes

Increased Functional Connectivity in the Default Mode Network in Mild Cognitive Impairment: A Maladaptive Compensatory Mechanism Associated with Poor Semantic Memory Performance

Semantic memory decline and changes of default mode network (DMN) connectivity have been reported in mild cognitive impairment (MCI). Only a few studies, however, have investigated the role of changes of activity in the DMN on semantic memory in this clinical condition. The present study aimed to investigate more extensively the relationship between semantic memory impairment and DMN intrinsic connectivity in MCI. Twenty-one MCI patients and 21 healthy elderly controls matched for demographic variables took part in this study. All participants underwent a comprehensive semantic battery including tasks of category fluency, visual naming and naming from definition for objects, actions and famous people, word-association for early and late acquired words and reading. A subgroup of the original sample (16 MCI patients and 20 healthy elderly controls) was also scanned with resting state functional magnetic resonance imaging and DMN connectivity was estimated using a seed-based approach. Compared with healthy elderly, patients showed an extensive semantic memory decline in category fluency, visual naming, naming from definition, words-association, and reading tasks. Patients presented increased DMN connectivity between the medial prefrontal regions and the posterior cingulate and between the posterior cingulate and the parahippocampus and anterior hippocampus. MCI patients also showed a significant negative correlation of medial prefrontal gyrus connectivity with parahippocampus and posterior hippocampus and visual naming performance. Our findings suggest that increasing DMN connectivity may contribute to semantic memory deficits in MCI, specifically in visual naming. Increased DMN connectivity with posterior cingulate and medio-temporal regions seems to represent a maladaptive reorganization of brain functions in MCI, which detrimentally contributes to cognitive impairment in this clinical population

Cognitive stimulation of the default-mode network modulates functional connectivity in healthy aging

A cognitive-stimulation tool was created to regulate functional connectivity within the brain Default-Mode Network (DMN). Computerized exercises were designed based on the hypothesis that repeated task-dependent coactivation of multiple DMN regions would translate into regulation of resting-state network connectivity. Forty seniors (mean age: 65.90 years; SD: 8.53) were recruited and assigned either to an experimental group (n = 21) who received one month of intensive cognitive stimulation, or to a control group (n = 19) who maintained a regime of daily-life activities explicitly focused on social interactions. An MRI protocol and a battery of neuropsychological tests were administered at baseline and at the end of the study. Changes in the DMN (measured via functional connectivity of posterior-cingulate seeds), in brain volumes, and in cognitive performance were measured with mixed models assessing group-by-timepoint interactions. Moreover, regression models were run to test gray-matter correlates of the various stimulation tasks. Significant associations were found between task performance and gray-matter volume of multiple DMN core regions. Training-dependent up-regulation of functional connectivity was found in the posterior DMN component. This interaction was driven by a pattern of increased connectivity in the training group, while little or no up-regulation was seen in the control group. Minimal changes in brain volumes were found, but there was no change in cognitive performance. The training-dependent regulation of functional connectivity within the posterior DMN component suggests that this stimulation program might exert a beneficial impact in the prevention and treatment of early AD neurodegeneration, in which this neurofunctional pathway is progressively affected by the disease

Separations technology development to support accelerator-driven transmutation concepts

This is the final report of a one-year Laboratory-Directed Research and Development (LDRD) Project at the Los Alamos National Laboratory (LANL). This project investigated separations technology development needed for accelerator-driven transmutation technology (ADTT) concepts, particularly those associated with plutonium disposition (accelerator-based conversion, ABC) and high-level radioactive waste transmutation (accelerator transmutation of waste, ATW). Specific focus areas included separations needed for preparation of feeds to ABC and ATW systems, for example from spent reactor fuel sources, those required within an ABC/ATW system for material recycle and recovery of key long-lived radionuclides for further transmutation, and those required for reuse and cleanup of molten fluoride salts. The project also featured beginning experimental development in areas associated with a small molten-salt test loop and exploratory centrifugal separations systems

Development of the accelerator-driven energy production concept

This is the final report of a three-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). Accelerator Driven Transmutation Technology (ADTT) offers a means of generating nuclear energy in a clean, safe way that can be attractive to the general public. However, there are issues associated with the energy story (both at the system level and technical detail) that have to be seriously addressed before the scientific community, the public, and potential industrial sponsors can be compellingly convinced of its cost/benefit

Memory difficulties are not always a sign of incipient dementia: a review of the possible causes of loss of memory efficiency

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Tunable Reflectarray Cell for Wide Angle Beam-Steering Radar Applications

An electronically tunable reflectarray element is proposed in this work to design beam-steering antennas useful for radar applications. A reduced size reflectarray unit cell is properly synthesized in order to extend the antenna beam scanning capabilities within a wider angular region. The radiating structure is accurately optimized to provide a full phase tuning range by adopting a single varactor load as phase shifter element. A 0.46 -reflectarray cell is designed at the frequency of 11.5 GHz, obtaining a phase agility of about 330 ∘ . The cell is successfully adopted for the design of a 21 × 21 reconfigurable reflectarray. The antenna is numerically tested for different configurations of the varactors capacitance values, and good beam-steering performances are demonstrated within a wide angular range

Safety, tolerability, and nocebo phenomena during transcranial magnetic stimulation: a systematic review and meta‐analysis of placebo‐controlled clinical trials

Background The methodology used for the application of repetitive transcranial magnetic stimulation (TMS) is such that it may induce a placebo effect. Respectively, adverse events (AEs) can occur when using a placebo, a phenomenon called nocebo. The primary aim of our meta‐analysis is to establish the nocebo phenomena during TMS. Safety and tolerability of TMS were also studied. Methods After a systematic Medline search for TMS randomized controlled trials (RCTs), we assessed the number of patients reporting at least one AE and the number of discontinuations because of AE in active and sham TMS groups. Results Data were extracted from 93 RCTs. The overall pooled estimate of active TMS and placebo treated patients who discontinued treatment because of AEs was 2.5% (95% CI 1.9%‐3.2%) and 2.7% (95% CI 2.0%‐3.5%), respectively. The pooled estimate of active TMS and placebo treated patients experiencing at least one AE was 29.3% (95% CI 19.0%‐22.6%) and 13.6% (95% CI 11.6%‐15.8%), respectively, suggesting that the odds of experiencing an AE is 2.60 times higher (95% CI 1.75‐3.86) in the active treatment group compared to placebo (p < 0.00001). The most common AE was headache, followed by dizziness. Secondary meta‐analyses in depression and psychotic disorders showed that the odds of experiencing an AE is 3.98 times higher (95% CI 2.14‐7.40) and 2.93 times higher (95% CI 1.41‐6.07), respectively, in the active treatment groups compared to placebo. Conclusions TMS is a safe and well‐tolerated intervention. Nocebo phenomena do occur during TMS treatment and should be acknowledged during clinical trial design and daily clinical practice