A systematic review of neuropsychiatric symptoms in mild cognitive impairment

Mild cognitive impairment (MCI) is a clinical concept proposed as an intermediate state between normal aging and dementia. This condition has multiple heterogeneous sources, including clinical presentation, etiology, and prognosis. Recently, the prevalence and associated features of neuropsychiatric symptoms (NPS) in MCI have been described. We systematically searched the PubMed database (last accessed on August 31, 2008) for articles on NPS in MCI. Included articles used strict selection criteria, and outcome variables were extracted in duplicate; of the 27 articles included, 14 (52%) used prospective cohorts. The global prevalence of NPS in MCI ranged from 35% to 85%. The most common behavioral symptoms were depression, anxiety, and irritability. Hospital-based samples reported a higher global prevalence of NPS than population-based studies; this discrepancy probably reflected differences in demographics, study setting, MCI diagnostic criteria, and behavioral instruments used. Prospective studies showed that NPS, particularly depression, may represent risk factors for MCI or predictors for the conversion of MCI to Alzheimer's disease (AD). NPS are very prevalent in subjects with MCI, displaying a similar pattern of symptoms compared to dementia and AD. Large cohort studies using standardized MCI criteria and behavioral instruments are required to evaluate the prognostic role of NPS in MCI.Mild cognitive impairment (MCI) is a clinical concept proposed as an intermediate state between normal aging and dementia. This condition has multiple heterogeneous sources, including clinical presentation, etiology, and prognosis. Recently, the prevalence and associated features of neuropsychiatric symptoms (NPS) in MCI have been described. We systematically searched the PubMed database (last accessed on August 31, 2008) for articles on NPS in MCI. Included articles used strict selection criteria, and outcome variables were extracted in duplicate; of the 27 articles included, 14 (52%) used prospective cohorts. The global prevalence of NPS in MCI ranged from 35% to 85%. The most common behavioral symptoms were depression, anxiety, and irritability. Hospital-based samples reported a higher global prevalence of NPS than population-based studies; this discrepancy probably reflected differences in demographics, study setting, MCI diagnostic criteria, and behavioral instruments used. Prospective studies showed that NPS, particularly depression, may represent risk factors for MCI or predictors for the conversion of MCI to Alzheimer’s disease (AD). NPS are very prevalent in subjects with MCI, displaying a similar pattern of symptoms compared to dementia and AD. Large cohort studies using standardized MCI criteria and behavioral instruments are required to evaluate the prognostic role of NPS in MC

Microearthquake moment tensors from the Coso Geothermal area

The Coso geothermal area, California, has produced hot water and steam for electricity generation for more than 20 years, during which time there has been a substantial amount of microearthquake activity in the area. Seismicity is monitored by a high-quality permanent network of 16 three-component digital borehole seismometers operated by the US Navy and supplemented by a ~ 14-station portable array of surface three-component digital instruments. The portable stations improve focal sphere coverage, providing seismic-wave polarity and amplitude data sets sufficient for determining full moment-tensor microearthquake mechanisms by the linearprogramming inversion method. We have developed a GUI-based interface to this inversion software that greatly increases its ease of use and makes feasible analyzing larger numbers of earthquakes than previously was practical. We show examples from an injection experiment conducted in well 34-9RD2, on the East Flank of the Coso geothermal area. This tight well was re-drilled February – March 2005 with the intention of hydrofracturing it, but instead, pervasive porosity and fractures were encountered at about 2660 m depth. Total drilling mud losses occurred, obviating the need to stimulate the well. These mud losses induced a 50-minute swarm of 44 microearthquakes, with magnitudes in the range -0.3 to 2.6. Most of the largest microearthquakes occurred in the first 2 minutes. Accurate relative relocations and moment tensors for the best-recorded subset reveal fine details of the fracture that was stimulated. This comprised a fault striking at N 20° E and dipping at 75° to the WNW, which propagated to the NNE and upward. Co-injection focal mechanisms reveal combined crack-opening and shear motion. Stress release and mode of failure differed between the pre-, co- and post-swarm periods. Some post-swarm events involved cavity collapse, suggesting that some of the cavity opening caused by the fluid injection was quickly reversed. Stress & mode of failure had not returned to pre-swarm conditions within 1 month following the injection, posing the question of how long stress perturbations persist following a stimulation experiment. This question may be answered by processing data spanning a longer postinjection period, work that is currently underway and will be reported in this presentation

Time-dependent seismic tomography and its application to the Coso geothermal area, 1996-2006

Measurements of temporal changes in Earth structure are commonly determined using localearthquake tomography computer programs that invert multiple seismic-wave arrival time data sets separately and assume that any differences in the structural results arise from real temporal variations. This assumption is dangerous because the results of repeated tomography experiments would differ even if the structure did not change, simply because of variation in the seismic ray distribution caused by the natural variation in earthquake locations. Even if the source locations did not change (if only explosion data were used, for example), derived structures would inevitably differ because of observational errors. A better approach is to invert multiple data sets simultaneously, which makes it possible to determine what changes are truly required by the data. This problem is similar to that of seeking models consistent with initial assumptions, and techniques similar to the “damped least squares” method can solve it. We have developed a computer program, dtomo, that inverts multiple epochs of arrival-time measurements to determine hypocentral parameters and structural changes between epochs. We shall apply this program to data from the seismically active Coso geothermal area, California, in the near future. The permanent network operated there by the US Navy, supplemented by temporary stations, has provided excellent earthquake arrival-time data covering a span of more than a decade. Furthermore, structural change is expected in the area as a result of geothermal exploitation of the resource. We have studied the period 1996 through 2006. Our results to date using the traditional method show, for a 2-km horizontal grid spacing, an irregular strengthening with time of a negative VP/VS anomaly in the upper ~ 2 km of the reservoir. This progressive reduction in VP/VS results predominately from an increase of VS with respect to VP. Such a change is expected to result from effects of geothermal operations such as decreasing fluid pressure and the drying of argillaceous minerals such as illite

Seismic monitoring of EGS tests at the Coso Geothermal area, California, using accurate MEQ locations and full moment tensors

We studied high-resolution relative locations and full moment tensors of microearthquakes (MEQs) occurring before, during and following Enhanced Geothermal Systems (EGS) experiments in two wells at the Coso geothermal area, California. The objective was to map new fractures, determine the mode and sense of failure, and characterize the stress cycle associated with injection. New software developed for this work combines waveform crosscorrelation measurement of arrival times with relative relocation methods, and assesses confidence regions for moment tensors derived using linearprogramming methods. For moment tensor determination we also developed a convenient Graphical User Interface (GUI), to streamline the work. We used data from the U.S. Navy’s permanent network of three-component digital borehole seismometers and from 14 portable three-component digital instruments. The latter supplemented the permanent network during injection experiments in well 34A-9 in 2004 and well 34-9RD2 in 2005. In the experiment in well 34A-9, the co-injection earthquakes were more numerous, smaller, more explosive and had more horizontal motion, compared with the pre-injection earthquakes. In the experiment in well 34-9RD2 the relocated hypocenters reveal a well-defined planar structure, 700 m long and 600 m high in the depth range 0.8 to 1.4 km below sea level, striking N 20° E and dipping at 75° to the WNW. The moment tensors show that it corresponds to a mode I (opening) crack. For both wells, the perturbed stress state near the bottom of the well persisted for at least two months following the injection

Biomarkers of oxidative and nitrosative damage in Alzheimer's disease and mild cognitive impairment

Alzheimer's disease (AD) is the most common type of dementia in the elderly. Products of oxidative and nitrosative stress (OS and NS, respectively) accumulate with aging, which is the main risk factor for AD. This provides the basis for the involvement of OS and NS in AD pathogenesis. OS and NS occur in biological systems due to the dysregulation of the redox balance, caused by a deficiency of antioxidants and/or the overproduction of free radicals. Free radical attack against lipids, proteins, sugars and nucleic acids leads to the formation of bioproducts whose detection in fluids and tissues represents the currently available method for assessing oxidative/nitrosative damage. Post-mortem and in-vivo studies have demonstrated an accumulation of products of free radical damage in the central nervous system and in the peripheral tissues of subjects with AD or mild cognitive impairment (MCI). In addition to their individual role, biomarkers for OS and NS in AD are associated with altered bioenergetics and amyloid-beta (Aβ) metabolism. In this review we discuss the main results obtained in the field of biomarkers of oxidative/nitrosative stress in AD and MCI in humans, in addition to their potential role as a tool for diagnosis, prognosis and treatment efficacy in AD. © 2009 Elsevier Ireland Ltd. All rights reserved

Attenuation and Source Properties at the Coso Geothermal Area, California

We use a multiple-empirical Green's function method to determine source properties of small (M −0.4 to 1.3) earthquakes and P- and S-wave attenuation at the Coso Geothermal Field, California. Source properties of a previously identified set of clustered events from the Coso geothermal region are first analyzed using an empirical Green's function (EGF) method. Stress-drop values of at least 0.5-1 MPa are inferred for all of the events; in many cases, the corner frequency is outside the usable bandwidth, and the stress drop can only be constrained as being higher than 3 MPa. P- and S-wave stress-drop estimates are identical to the resolution limits of the data. These results are indistinguishable from numerous EGF studies of M 2-5 earthquakes, suggesting a similarity in rupture processes that extends to events that are both tiny and induced, providing further support for Byerlee's Law. Whole-path Q estimates for P and S waves are determined using the multiple-empirical Green's function (MEGF) method of Hough (1997), whereby spectra from clusters of colocated events at a given station are inverted for a single attenuation parameter, κ, with source parameters constrained from EGF analysis. The κ estimates, which we infer to be resolved to within 0.01 sec or better, exhibit almost as much scatter as a function of hypocentral distance as do values from previous single-spectrum studies for which much higher uncertainties in individual κ estimates are expected. The variability in κ estimates determined here therefore suggests real lateral variability in Q structure. Although the ray-path coverage is too sparse to yield a complete three-dimensional attenuation tomographic image, we invert the inferred κ value for three-dimensional structure using a damped least-squares method, and the results do reveal significant lateral variability in Q structure. The inferred attenuation variability corresponds to the heat-flow variations within the geothermal region. A central low-Q region corresponds well with the central high-heat flow region; additional detailed structure is also suggested

Transcranial random noise stimulation over the primary motor cortex in PD-MCI patients: a crossover, randomized, sham-controlled study

Mild cognitive impairment (MCI) is a very common non-motor feature of Parkinson’s disease (PD) and the non-amnestic single-domain is the most frequent subtype. Transcranial random noise stimulation (tRNS) is a non-invasive technique, which is capable of enhancing cortical excitability. As the main contributor to voluntary movement control, the primary motor cortex (M1) has been recently reported to be involved in higher cognitive functioning. The aim of this study is to evaluate the effects of tRNS applied over M1 in PD-MCI patients in cognitive and motor tasks. Ten PD-MCI patients, diagnosed according to the Movement Disorder Society, Level II criteria for MCI, underwent active (real) and placebo (sham) tRNS single sessions, at least 1 week apart. Patients underwent cognitive (Digit Span Forward and Backward, Digit Symbol, Visual Search, Letter Fluency, Stroop Test) and motor assessments (Unified Parkinson’s Disease Rating Scale [UPDRS-ME], specific timed trials for bradykinesia, 10-m walk and Timed up and go tests) before and after each session. A significant improvement in motor ability (UPDRS-ME and lateralized scores, ps from 0.049 to 0.003) was observed after real versus sham tRNS. On the contrary, no significant differences were found in other motor tasks and cognitive assessment both after real and sham stimulations. These results confirm that tRNS is a safe and effective tool for improving motor functioning in PD-MCI. Future studies using a multisession tRNS applied over multitargeted brain areas (i.e., dorsolateral prefrontal cortex and M1) are required to clarify the role of tRNS regarding rehabilitative intervention in PD

Time-dependent seismic tomography of the Coso geothermal area, 1996-2004

Local-earthquake tomographic images were calculated for each of the years 1996 - 2004 using arrival times from the U.S. Navy’s permanent seismometer network at the Coso geothermal area, California. The results show irregular strengthening with time of the wave-speed ratio VP/VS at shallow depths. These changes result predominately from progressive relative increase in VS with respect to VP, and could result from processes associated with geothermal operations such as decrease in fluid pressure and the drying of argillaceous minerals such as illite

SHIP2: A ‘‘NEW’’ Insulin Pathway Target for Aging Research

Strong evidence suggests that systemic inflammation and central adiposity contribute to and perpetuate metabolic syndrome. All of these alterations predispose individuals to type 2 diabetes mellitus (T2DM), cardiovascular disease, as well as Alzheimer’s disease (AD), all characterized by chronic inflammatory status. On the other hand, extensive abnormalities in insulin and insulin-like growth factor I (IGF-I) and IGF-II signaling mechanisms in brains with AD have been demonstrated, suggesting that AD could be a third form of diabetes. The Src homology domain-containing inositol 5-phosphatase 2 (SHIP2) has an important role in the insulin pathway because its over-expression causes impairment of insulin/IGF-1 signaling. Because some singlenucleotide polymorphisms (SNP) of the gene encoding SHIP2 were significantly associated in T2DM patients with metabolic syndrome and some related conditions, we decided to conduct a case–control study on this gene, analyzing AD and T2DM subjects as cases and young, old, and centenarians as controls. Our results suggest a putative correlation between the the rs144989913 SNP and aging, both successful and unsuccessful, rather than age-related diseases. Because this SNP is an insertion/deletion of 28 bp, it might cause an alteration in SHIP2 expression. It is noteworthy that SHIP2 has been demonstrated to be a potent negative regulator of insulin signaling and insulin sensitivity. Many studies demonstrated the association of the insulin/IGF1 pathway with aging and longevity, so it is tempting to speculate that the found association with SHIP2 and aging might depend on its effect on the insulin/IGF-1 pathwa

Frequency and Correlates of Mild Cognitive Impairment in Myasthenia Gravis

Background: Antibodies against acetylcholine receptors (AChRs) can also target nicotinic AChRs that are present throughout the central nervous system, thus leading to cognitive dysfunctions in patients with myasthenia gravis (MG). However, the presence of cognitive impairment in MG is controversial, and the factors that may influence this risk are almost completely unknown. In this study, the frequency of mild cognitive impairment (MCI) in MG, as well as the clinical, immunological, and behavioral correlates of MCI in MG were evaluated. Methods: A total of 52 patients with MG underwent a comprehensive assessment including motor and functional scales, serological testing, and neuropsychological and behavioral evaluation. Results: The frequency of MCI was 53.8%, and the most impaired cognitive domains were, in order, visuoconstructive/visuospatial skills, memory, and attention. After multivariate analysis, only pyridostigmine use was inversely associated with the presence of MCI, while a trend toward a positive association between MCI and disease severity and arms/legs hyposthenia was found. Correlation analyses showed that daily doses of prednisone and azathioprine significantly correlated with depressive symptomatology, while disease severity significantly correlated with depressive symptomatology and sleep disturbance. Conclusions: The presence of MCI is rather frequent in MG and is characterized by multidomain amnestic impairment. Such preliminary data need further confirmation on larger case series