Cognitive aging in persons with minimal amyloid-β and white matter hyperintensities

Substantial individual differences exist in the magnitude of the cognitive decline associated with normal aging. Potential contributors to this intersubject variability include white matter hyperintensities (WMH) and preclinical Alzheimer′s disease, evident as increased brain amyloid. This study examined whether older individuals with minimal evidence of WMH and/or brain amyloid-beta (seen on positron emission tomography with the Pittsburgh compound B radiotracer—PiB) still showed significant cognitive decrements compared to the young. Older individuals, conservatively screened for normal range performance on an extensive neuropsychological battery, underwent structural magnetic resonance imaging (MRI) and PiB scans and performed tests of information processing speed, working memory and inhibitory function. The elderly were divided into PiB(+) and PiB(−) groups based on radiotracer retention. There were no significant differences in cognitive performance between PiB(+) and PiB(−) elderly. However, both PiB groups performed significantly worse than did the young on cognitive testing. WMH burden in the same individuals was quantified by consensus ratings using a 10 point scale with a median split defining two groups, WMH(+) and WMH(−). There were no differences in cognitive performance between WMH(+) and WMH(−) individuals, but both WMH groups performed significantly worse than did the young. Older participants who were both PiB(−) and WMH(−) also performed significantly worse than did the young in all three cognitive domains. The present results suggest that normal-elderly individuals whose brain scans show minimal evidence of amyloid deposition or WMH, still demonstrate a major decrement in comparison to younger persons on measures of processing resources and inhibitory efficiency.     

Fusion of white and gray matter geometry: A framework for investigating brain development

Current neuroimaging investigation of the white matter typically focuses on measurements derived from diffusion tensor imaging, such as fractional anisotropy (FA). In contrast, imaging studies of the gray matter oftentimes focus on morphological features such as cortical thickness, folding and surface curvature. As a result, it is not clear how to combine findings from these two types of approaches in order to obtain a consistent picture of morphological changes in both gray and white matter.In this paper, we propose a joint investigation of gray and white matter morphology by combining geometrical information from white and the gray matter. To achieve this, we first introduce a novel method for computing multi-scale white matter tract geometry. Its formulation is based on the differential geometry of curve sets and is easily incorporated into a continuous scale-space framework.We then incorporate this method into a novel framework for “fusing” white and gray matter geometrical information. Given a set of fiber tracts originating in a particular cortical region, the key idea is to compute two scalar fields that represent geometrical characteristics of the white matter and of the surface of the cortical region. A quantitative marker is created by combining the distributions of these scalar values using Mutual Information. This marker can be then used in the study of normal and pathological brain structure and development. We apply this framework to a study on autism spectrum disorder in children. Our preliminary results support the view that autism may be characterized by early brain overgrowth, followed by reduced or arrested growth (Courchesne, 2004).     

Environmental Inequality in Exposures to Airborne Particulate Matter Components in the United States

Background: Growing evidence indicates that toxicity of fine particulate matter ≤ 2.5 μm in diameter (PM_2.5) differs by chemical component. Exposure to components may differ by population.Objectives: We investigated whether exposures to PM_2.5 components differ by race/ethnicity, age, and socioeconomic status (SES).Methods: Long-term exposures (2000 through 2006) were estimated for 215 U.S. census tracts for PM_2.5 and for 14 PM_2.5 components. Population-weighted exposures were combined to generate overall estimated exposures by race/ethnicity, education, poverty status, employment, age, and earnings. We compared population characteristics for tracts with and without PM_2.5 component monitors.Results: Larger disparities in estimated exposures were observed for components than for PM_2.5 total mass. For race/ethnicity, whites generally had the lowest exposures. Non-Hispanic blacks had higher exposures than did whites for 13 of the 14 components. Hispanics generally had the highest exposures (e.g., 152% higher than whites for chlorine, 94% higher for aluminum). Young persons (0–19 years of age) had levels as high as or higher than other ages for all exposures except sulfate. Persons with lower SES had higher estimated exposures, with some exceptions. For example, a 10% increase in the proportion unemployed was associated with a 20.0% increase in vanadium and an 18.3% increase in elemental carbon. Census tracts with monitors had more non-Hispanic blacks, lower education and earnings, and higher unemployment and poverty than did tracts without monitors.Conclusions: Exposures to PM_2.5 components differed by race/ethnicity, age, and SES. If some components are more toxic than others, certain populations are likely to suffer higher health burdens. Demographics differed between populations covered and not covered by monitors.     

Characterization of Printed Circuit Boards for Metal and Energy Recovery after Milling and Mechanical Separation

The proper disposal of electrical and electronic waste is currently a concern of researchers and environmental managers not only because of the large volume of such waste generated, but also because of the heavy metals and toxic substances it contains. This study analyzed printed circuit boards (PCBs) from discarded computers to determine their metal content and characterized them as solid waste and fuel. The analysis showed that PCBs consist of approximately 26% metal, made up mainly of copper, lead, aluminum, iron and tin, as well as other heavy metals such as cadmium and nickel. Comparison with the results of other studies indicated that the concentration of precious metals (gold and silver) has declined over time. Analysis of the leachate revealed high concentrations of cadmium and lead, giving the residue the characteristics of hazardous waste. After milling the PCBs, we found that larger amounts of metal were concentrated in smaller fractions, while the lightest fraction, obtained by density separation, had a gross calorific value of approximately 11 MJ/kg, although with a high ash content. Milling followed by density separation proved potentially useful for recovery of metals and energy-rich fractions.     

Thalamic diffusion differences related to cognitive function in white matter lesions

Cerebral white matter lesions (WMLs) are related to cognitive deficits, probably due to a disruption of frontal–subcortical circuits. We explored thalamic diffusion differences related to white matter lesions (WMLs) and their association with cognitive function in middle-aged individuals. Ninety-six participants from the Barcelona-AsIA Neuropsychology Study were included. Participants were classified into groups based on low grade and high grade of periventricular hyperintensities (PVHs) and deep white matter hyperintensities (DWMHs). Tract-Based Spatial Statistics was used to study thalamic diffusion differences between groups. Mean fractional anisotropy (FA) values in significant areas were calculated for each subject and correlated with cognitive performance. Participants with high-grade PVHs and DWMHs showed lower FA thalamic values compared to those with low-grade PVHs and DWMHs, respectively. Decreased FA thalamic values in high-grade DWMHs, but not high-grade PVH, were related to lower levels of performance in psychomotor speed, verbal fluency, and visuospatial skills. Thalamic diffusion differences are related to lower cognitive function only in participants with high-grade DWMHs. These results support the hypothesis that fronto–subcortical disruption is associated with cognitive function only in DWMHs.     

Nonexponential T2* decay in white matter

Visualizing myelin in human brain may help the study of diseases such as multiple sclerosis. Previous studies based on T₁ and T₂ relaxation contrast have suggested the presence of a distinct water pool that may report directly on local myelin content. Recent work indicates that T₂* contrast may offer particular advantages over T₁ and T₂ contrast, especially at high field. However, the complex mechanism underlying T₂* relaxation may render interpretation difficult. To address this issue, T₂* relaxation behavior in human brain was studied at 3 and 7 T. Multiple gradient echoes covering most of the decay curve were analyzed for deviations from mono‐exponential behavior. The data confirm the previous finding of a distinct rapidly relaxing signal component (T₂* ～ 6 ms), tentatively attributed to myelin water. However, in extension to previous findings, this rapidly relaxing component displayed a substantial resonance frequency shift, reaching 36 Hz in the corpus callosum at 7 T. The component's fractional amplitude and frequency shift appeared to depend on both field strength and fiber orientation, consistent with a mechanism originating from magnetic susceptibility effects. The findings suggest that T₂* contrast at high field may be uniquely sensitive to tissue myelin content and that proper interpretation will require modeling of susceptibility‐induced resonance frequency shifts. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Embracing oligodendrocyte diversity in the context of perinatal injury

Emerging evidence is fueling a new appreciation of oligodendrocyte diversity that is overturning the tradi-tional view that oligodendrocytes are a homogenous cell population. Oligodendrocytes of distinct origins, maturational stages, and regional locations may differ in their functional capacity or susceptibility to injury. One of the most unique qualities of the oligodendrocyte is its ability to produce myelin. Myelin abnormali-ties have been ascribed to a remarkable array of perinatal brain injuries, with concomitant oligodendrocyte dysregulation. Within this review, we discuss new insights into the diversity of the oligodendrocyte lineage and highlight their relevance in paradigms of perinatal brain injury. Future therapeutic development will be informed by comprehensive knowledge of oligodendrocyte pathophysiology that considers the particular facets of heterogeneity that this lineage exhibits.     

Changes in lactate dehydrogenase are associated with central gray matter lesions in newborns with hypoxic-ischemic encephalopathy

Purpose: Biomarkers may predict neurological prognosis in infants with hypoxic-ischemic encephalopathy (HIE). We evaluated the relationship between serum lactate dehydrogenase (LDH) and brain magnetic resonance imaging (MRI), which predicts neurodevelopmental outcomes, in order to assess whether LDH levels are similarly predictive.

Materials and methods: Medical records were reviewed for infants with HIE and LDH levels were assessed on the first (LDH₁) and third (LDH₃) days following birth. Receiver operating characteristic curves were obtained in relation to central gray matter hypoxic-ischemic lesions.

Results: Of 92 patients, 52 (56.5%) had hypoxic-ischemic lesions on brain MRI, and 21 of these infants (40.4%) had central gray matter lesions. LDH₁ and LDH₃ did not differ; however, the percentage change (ΔLDH%) was significantly higher in infants with central gray matter lesions (36.9% versus 6.6%, p?=?0.006). With cutoffs of 187 (IU/L, ΔLDH) and 19.4 (%, ΔLDH%), the sensitivity, specificity, positive predictive value and negative predictive value were 71.4, 69.0, 40.5 and 89.1%, respectively. The relative risk was 5.57 (p?=?0.001).

Conclusion: Changes in serum LDH may be a useful biomarker for predicting future neurodevelopmental prognosis in infants with HIE.