Cognitive Reserve Associated with FDG-PET in Preclinical Alzheimer Disease

OBJECTIVE: To examine the effect of education (a surrogate measure of cognitive reserve) on FDG-PET brain metabolism in elderly cognitively healthy (HC) subjects with preclinical Alzheimer disease (AD). METHODS: Fifty-two HC subjects (mean age 75 years) with FDG-PET and CSF measurement of Abeta1-42 were included from the prospective Alzheimer's Disease Neuroimaging Initiative biomarker study. HC subjects received a research classification of preclinical AD if CSF Abeta1-42 was <192 pg/mL (Abeta1-42 [+]) vs HC with normal Abeta (Abeta1-42 [-]). In regression analyses, we tested the interaction effect between education and CSF Abeta1-42 status (Abeta1-42 [+] vs Abeta1-42 [-]) on FDG-PET metabolism in regions of interest (ROIs) (posterior cingulate, angular gyrus, inferior/middle temporal gyrus) and the whole brain (voxel-based). RESULTS: An interaction between education and CSF Abeta1-42 status was observed for FDG-PET in the posterior cingulate (p < 0.001) and angular gyrus ROIs (p = 0.03), but was not significant for the inferior/middle temporal gyrus ROI (p = 0.06), controlled for age, sex, and global cognitive ability (Alzheimer's Disease Assessment Scale-cognitive subscale). The interaction effect was such that higher education was associated with lower FDG-PET in the Abeta1-42 (+) group, but with higher FDG-PET in the Abeta1-42 (-) group. Voxel-based analysis showed that this interaction effect was primarily restricted to temporo-parietal and ventral prefrontal brain areas. CONCLUSIONS: Higher education was associated with lower FDG-PET in preclinical AD (Abeta1-42 [+]), suggesting that cognitive reserve had a compensatory function to sustain cognitive ability in presence of early AD pathology that alters FDG-PET metabolism

Observation of Coulomb-Assisted Dipole-Forbidden Intraexciton Transitions in Semiconductors

We use terahertz pulses to induce resonant transitions between the eigenstates of optically generated exciton populations in a high-quality semiconductor quantum-well sample. Monitoring the excitonic photoluminescence, we observe transient quenching of the $1s$ exciton emission, which we attribute to the terahertz-induced $1s$-to-$2p$ excitation. Simultaneously, a pronounced enhancement of the $2s$-exciton emission is observed, despite the $1s$-to-$2s$ transition being dipole forbidden. A microscopic many-body theory explains the experimental observations as a Coulomb-scattering mixing of the 2$s$ and 2$p$ states, yielding an effective terahertz transition between the 1$s$ and 2$s$ populations.Comment: 5 pages, 3 figure

Comparative Leaf Water Absorption Between Chaparral Island and Mainland Taxa: a Common Garden Experiment

In California and other Mediterranean-type ecosystems, island species are typically exposed to more fog but less rain than mainland species. Because adaptations to absorb water from fog may conflict with those to minimize water loss, we hypothesized that island species should have greater fog absorption than their mainland congeners due to foliar uptake but at the cost of modifying other leaf structural and functional traits. To determine whether foliar water absorption is an adaptation to insularity, we compared seven physiological and anatomical leaf traits between congeneric island and mainland species of two genera, Ceanothus and Arctostaphylos, in a common garden in Claremont, California. We quantified leaf water potentials, maximum leaf water absorption rates, leaf hydrophobicity, leaf mass per area [LMA], succulence, stomatal density, and wax morphology. All taxa exhibited water permeability through their leaf surfaces, but only one of the three island taxa showed greater water absorption than their mainland counterparts. The island and mainland varieties of C. megacarpus were similar in water absorption and hydrophobicity, but the mainland variety had greater LMA, greater succulence, and thicker epicuticular wax. In Arctostaphylos, insularity promoted species-specific responses: A. catalinae had greater foliar absorption compared to the mainland species, whereas A. insularis displayed mesophytic traits such as hypostomatal morphology, horizontally oriented leaves and low LMA. Relative surface hydrophobicity was not linked to absorption rates, but the mainland species A. glauca had the most hydrophobic leaf surfaces in the study, achieved by their ornate epicuticular wax. Overall, island taxa displayed more mesophytic leaf traits than their mainland congeners. The results may have implications for biogeography in Mediterranean-type ecosystems that may be losing seasonal coastal fog with global change

Multiple indices of diffusion identifies white matter damage in mild cognitive impairment and Alzheimer's disease

The study of multiple indices of diffusion, including axial (DA), radial (DR) and mean diffusion (MD), as well as fractional anisotropy (FA), enables WM damage in Alzheimer's disease (AD) to be assessed in detail. Here, tract-based spatial statistics (TBSS) were performed on scans of 40 healthy elders, 19 non-amnestic MCI (MCIna) subjects, 14 amnestic MCI (MCIa) subjects and 9 AD patients. Significantly higher DA was found in MCIna subjects compared to healthy elders in the right posterior cingulum/precuneus. Significantly higher DA was also found in MCIa subjects compared to healthy elders in the left prefrontal cortex, particularly in the forceps minor and uncinate fasciculus. In the MCIa versus MCIna comparison, significantly higher DA was found in large areas of the left prefrontal cortex. For AD patients, the overlap of FA and DR changes and the overlap of FA and MD changes were seen in temporal, parietal and frontal lobes, as well as the corpus callosum and fornix. Analysis of differences between the AD versus MCIna, and AD versus MCIa contrasts, highlighted regions that are increasingly compromised in more severe disease stages. Microstructural damage independent of gross tissue loss was widespread in later disease stages. Our findings suggest a scheme where WM damage begins in the core memory network of the temporal lobe, cingulum and prefrontal regions, and spreads beyond these regions in later stages. DA and MD indices were most sensitive at detecting early changes in MCIa

Global impacts of energy demand on the freshwater resources of nations

The growing geographic disconnect between consumption of goods, the extraction and processing of resources, and the environmental impacts associated with production activities makes it crucial to factor global trade into sustainability assessments. Using an empirically validated environmentally extended global trade model, we examine the relationship between two key resources underpinning economies and human well-being—energy and freshwater. A comparison of three energy sectors (petroleum, gas, and electricity) reveals that freshwater consumption associated with gas and electricity production is largely confined within the territorial boundaries where demand originates. This finding contrasts with petroleum, which exhibits a varying ratio of territorial to international freshwater consumption, depending on the origin of demand. For example, although the United States and China have similar demand associated with the petroleum sector, international freshwater consumption is three times higher for the former than the latter. Based on mapping patterns of freshwater consumption associated with energy sectors at subnational scales, our analysis also reveals concordance between pressure on freshwater resources associated with energy production and freshwater scarcity in a number of river basins globally. These energy-driven pressures on freshwater resources in areas distant from the origin of energy demand complicate the design of policy to ensure security of fresh water and energy supply. Although much of the debate around energy is focused on greenhouse gas emissions, our findings highlight the need to consider the full range of consequences of energy production when designing policy

The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory

© 2019, The Author(s). The single nucleotide polymorphism (SNP) rs744373 in the bridging integrator-1 gene (BIN1) is a risk factor for Alzheimer’s disease (AD). In the brain, BIN1 is involved in endocytosis and sustaining cytoskeleton integrity. Post-mortem and in vitro studies suggest that BIN1-associated AD risk is mediated by increased tau pathology but whether rs744373 is associated with increased tau pathology in vivo is unknown. Here we find in 89 older individuals without dementia, that BIN1 rs744373 risk-allele carriers show higher AV1451 tau-PET across brain regions corresponding to Braak stages II–VI. In contrast, the BIN1 rs744373 SNP was not associated with AV45 amyloid-PET uptake. Furthermore, the rs744373 risk-allele was associated with worse memory performance, mediated by increased global tau levels. Together, our findings suggest that the BIN1 rs744373 SNP is associated with increased tau but not beta-amyloid pathology, suggesting that alterations in BIN1 may contribute to memory deficits via increased tau pathology

Robust automated detection of microstructural white matter degeneration in Alzheimer’s disease using machine learning classification of multicenter DTI data

Diffusion tensor imaging (DTI) based assessment of white matter fiber tract integrity can support the diagnosis of Alzheimer’s disease (AD). The use of DTI as a biomarker, however, depends on its applicability in a multicenter setting accounting for effects of different MRI scanners. We applied multivariate machine learning (ML) to a large multicenter sample from the recently created framework of the European DTI study on Dementia (EDSD). We hypothesized that ML approaches may amend effects of multicenter acquisition. We included a sample of 137 patients with clinically probable AD (MMSE 20.6±5.3) and 143 healthy elderly controls, scanned in nine different scanners. For diagnostic classification we used the DTI indices fractional anisotropy (FA) and mean diffusivity (MD) and, for comparison, gray matter and white matter density maps from anatomical MRI. Data were classified using a Support Vector Machine (SVM) and a Naïve Bayes (NB) classifier. We used two cross-validation approaches, (i) test and training samples randomly drawn from the entire data set (pooled cross-validation) and (ii) data from each scanner as test set, and the data from the remaining scanners as training set (scanner-specific cross-validation). In the pooled cross-validation, SVM achieved an accuracy of 80% for FA and 83% for MD. Accuracies for NB were significantly lower, ranging between 68% and 75%. Removing variance components arising from scanners using principal component analysis did not significantly change the classification results for both classifiers. For the scanner-specific cross-validation, the classification accuracy was reduced for both SVM and NB. After mean correction, classification accuracy reached a level comparable to the results obtained from the pooled cross-validation. Our findings support the notion that machine learning classification allows robust classification of DTI data sets arising from multiple scanners, even if a new data set comes from a scanner that was not part of the training sample

Correspondence Between Resting-State and Episodic Memory-Task Related Networks in Elderly Subjects

Resting-state fMRI studies demonstrated temporally synchronous fluctuations in brain activity among ensembles of brain regions, suggesting the existence of intrinsic functional networks. A spatial match between some of the resting-state networks and regional brain activation during cognitive tasks has been noted, suggesting that resting-state networks support particular cognitive abilities. However, the spatial match and predictive value of any resting-state network and regional brain activation during episodic memory is only poorly understood. In order to address this research gap, we obtained fMRI acquired both during rest and a face-name association task in 38 healthy elderly subjects. In separate independent component analyses, networks of correlated brain activity during rest or the episodic memory task were identified. For the independent components identified for task-based fMRI, the design matrix of successful encoding or retrieval trials was regressed against the time course of each of the component to identify significantly activated networks. Spatial regression was used to assess the match of resting-state networks against those related to successful memory encoding or retrieval. We found that resting-state networks covering the medial temporal, middle temporal, and frontal areas showed increased activity during successful encoding. Resting-state networks located within posterior brain regions showed increased activity during successful recognition. However, the level of resting-state network connectivity was not predictive of the task-related activity in these networks. These results suggest that a circumscribed number of functional networks detectable during rest become engaged during successful episodic memory. However, higher intrinsic connectivity at rest may not translate into higher network expression during episodic memory

The B subunits of cholera and Escherichia coli heat-labile toxins enhance the immune responses in mice orally immunised with a recombinant live P-fimbrial vaccine for avian pathogenic E. coli

This study aimed to investigate the adjuvant effect of recombinant attenuated Salmonella expressing cholera toxin B subunit (CTB) and Escherichia coli heat-labile enterotoxin B subunit (LTB) for the P-fimbriae subunit-based vaccine of avian pathogenic E. coli (APEC) in a murine model. The PapA-specific sIgA and IgG responses were significantly enhanced after immunisation with the Salmonella-PapA vaccine in the presence of CTB or LTB. The group immunised with the Salmonella-LTB strain promoted Th1-type immunity, whereas that immunised with the Salmonella-CTB strain produced Th2-type immunity. We concluded that both Salmonella-CTB and -LTB strains can enhance the immune response to PapA, and that the LTB strain may be a more effective adjuvant for APEC vaccination, which requires higher Th1-type immunity for protection. Thus, our findings provide evidence that immunisation with an adjuvant, LTB, is one of the strategies of developing effective vaccines against P-fimbriated APEC

The left frontal cortex supports reserve in aging by enhancing functional network efficiency

Background: Recent evidence from fMRI studies suggests that functional hubs, i.e. highly connected brain regions, are important for mental health. We found recently that global connectivity of a hub in the left frontal cortex (LFC-connectivity) is associated with relatively preserved memory abilities and higher levels of protective factors (education, IQ) in normal aging and Alzheimer’s disease. These results suggest that LFC-connectivity supports reserve capacity alleviating memory decline. An open question is, however, why LFC-connectivity is beneficial and supports memory function in the face of neurodegeneration. We hypothesized that higher LFCconnectivity is associated with enhanced efficiency in connected major networks involved in episodic memory. We further hypothesized that higher LFC-related network efficiency predicts higher memory abilities. Methods: We assessed fMRI during a face-name association learning task in 26 healthy cognitively normal elderly participants. Using beta-series correlation analysis, we computed task-related LFC-connectivity to key memory networks including the default-mode network (DMN) and dorsal attention network (DAN). Network efficiency within the DMN and DAN was estimated by the graph theoretical small-worldness statistic. We applied linear regression analyses in order to test the association between LFC-connectivity to the DMN/DAN and small-worldness of these networks. Mediation analysis was applied to test LFC-connectivity to the DMN and DAN as a mediator of the association between education and higher DMN and DAN smallworldness. Lastly, we tested network small-worldness as a predictor of memory performance. Results: We found that higher LFC-connectivity to the DMN and DAN during successful memory encoding and recognition was associated with higher small-worldness of those networks. Higher task-related LFC-connectivity mediated the association between education and higher small-worldness in the DMN and DAN. Further, higher small-worldness of these networks predicted better performance in the memory task. Conclusions: The current results suggest that higher education-related LFC-connectivity to key memory networks during a memory task is associated with higher network efficiency and thus enhanced reserve of memory abilities in aging