Corrigendum

No abstrac

Impact of Genetic Variation in SORCS1 on Memory Retention

We previously reported that genetic variants in SORCS1 increase the risk of AD, that over-expression of SorCS1 reduces γ-secretase activity and Aβ levels, and that SorCS1 suppression increases γ-secretase processing of APP and Aβ levels. We now explored the effect of variation in SORCS1 on memory.We explored associations between SORCS1-SNPs and memory retention in the NIA-LOAD case control dataset (162 cases,670 controls) and a cohort of Caribbean Hispanics (549 cases,544 controls) using single marker and haplotype analyses.Three SNPs in intron 1, were associated with memory retention in the NIA-LOAD dataset or the Caribbean Hispanic dataset (rs10884402(A allele:β = -0.15,p = 0.008), rs7078098(C allele:β = 0.18,p = 0.007) and rs950809(C allele:β = 0.17,p = 0.008)) and all three SNPs were significant in a meta-analysis of both datasets (0.002<p<0.03). The corresponding A-T-T haplotype for these SNPs was associated with lower scores in both datasets (p = 0.02,p = 0.0009), and the complementary G-C-C haplotype was associated with higher scores in NIA-LOAD (p = 0.02). These associations were restricted to cases.Variation in intron 1 in SORCS1 is associated with memory changes in AD

Anemia and risk for cognitive decline in chronic kidney disease

BACKGROUND: Anemia is common among patients with chronic kidney disease (CKD) but its health consequences are poorly defined. The aim of this study was to determine the relationship between anemia and cognitive decline in older adults with CKD. METHODS: We studied a subgroup of 762 adults age ≥55 years with CKD participating in the Chronic Renal Insufficiency Cohort (CRIC) study. Anemia was defined according to the World Health Organization criteria (hemoglobin <13 g/dL for men and <12 g/dL for women). Cognitive function was assessed annually with a battery of six tests. We used logistic regression to determine the association between anemia and baseline cognitive impairment on each test, defined as a cognitive score more than one standard deviation from the mean, and mixed effects models to determine the relation between anemia and change in cognitive function during follow-up after adjustment for demographic and clinical characteristics. RESULTS: Of 762 participants with mean estimated glomerular filtration rate of 42.7 ± 16.4 ml/min/1.73 m(2), 349 (46 %) had anemia. Anemia was not independently associated with baseline cognitive impairment on any test after adjustment for demographic and clinical characteristics. Over a median 2.9 (IQR 2.6–3.0) years of follow-up, there was no independent association between anemia and change in cognitive function on any of the six cognitive tests. CONCLUSIONS: Among older adults with CKD, anemia was not independently associated with baseline cognitive function or decline. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12882-016-0226-6) contains supplementary material, which is available to authorized users

Mood is a key determinant of cognitive performance in community-dwelling older adults: a cross-sectional analysis

First Online: 06 October 2012Identification of predictors of cognitive trajectories through the establishment of composite or single-parameter dimensional categories of cognition and mood may facilitate development of strategies to improve quality of life in the elderly. Participants (n = 487, aged 50+ years) were representative of the Portuguese population in terms of age, gender, and educational status. Cognitive and mood profiles were established using a battery of neurocognitive and psychological tests. Data were subjected to principal component analysis to identify core dimensions of cognition and mood, encompassing multiple test variables. Dimensions were correlated with age and with respect to gender, education, and occupational status. Cluster analysis was applied to isolate distinct patterns of cognitive performance and binary logistic regression models to explore interrelationships between aging, cognition, mood, and socio-demographic characteristics. Four main dimensions were identified: memory, executive function, global cognitive status, and mood. Based on these, strong and weak cognitive performers were distinguishable. Cluster analysis revealed further distinction within these two main categories into very good, good, poor, and very poor performers. Mood was the principal factor contributing to the separation between very good and good, as well as poor and very poor, performers. Clustering was also influenced by gender and education, albeit to a lesser extent; notably, however, female gender × lower educational background predicted significantly poorer cognitive performance with increasing age. Mood has a significant impact on the rate of cognitive decline in the elderly. Gender and educational level are early determinants of cognitive performance in later life.This work was funded by the European Commission (FP7) “SwitchBox” (Contract HEALTH-F2-2010-259772). NCS is supported by a SwitchBox post-doctoral fellowship. We are thankful to all study participants. The authors would like to acknowledge all colleagues who assisted with participant recruitment and evaluation

Surface Feature-Guided Mapping of Cerebral Metabolic Changes in Cognitively Normal and Mildly Impaired Elderly

Purpose: The aim of this study was to investigate the longitudinal positron emission tomography (PET) metabolic changes in the elderly. Procedures: Nineteen nondemented subjects (mean Mini-Mental Status Examination 29.4±0.7 SD) underwent two detailed neuropsychological evaluations and resting 2-deoxy-2-[F-18]fluoro-D-glucose (FDG)-PET scan (interval 21.7±3.7 months), baseline structural 3T magnetic resonance (MR) imaging, and apolipoprotein E4 genotyping. Cortical PET metabolic changes were analyzed in 3-D using the cortical pattern matching technique. Results: Baseline vs. follow-up whole-group comparison revealed significant metabolic decline bilaterally in the posterior temporal, parietal, and occipital lobes and the left lateral frontal cortex. The declining group demonstrated 10–15 % decline in bilateral posterior cingulate/precuneus, posterior temporal, parietal, and occipital cortices. The cognitively stable group showed 2.5–5% similarly distributed decline. ApoE4-positive individuals underwent 5–15 % metabolic decline in the posterior association cortices. Conclusions: Using 3-D surface-based MR-guided FDG-PET mapping, significant metaboli

Role of Sphingomyelin Synthase in Controlling the Antimicrobial Activity of Neutrophils against Cryptococcus neoformans

The key host cellular pathway(s) necessary to control the infection caused by inhalation of the environmental fungal pathogen Cryptococcus neoformans are still largely unknown. Here we have identified that the sphingolipid pathway in neutrophils is required for them to exert their killing activity on the fungus. In particular, using both pharmacological and genetic approaches, we show that inhibition of sphingomyelin synthase (SMS) activity profoundly impairs the killing ability of neutrophils by preventing the extracellular release of an antifungal factor(s). We next found that inhibition of protein kinase D (PKD), which controls vesicular sorting and secretion and is regulated by diacylglycerol (DAG) produced by SMS, totally blocks the extracellular killing activity of neutrophils against C. neoformans. The expression of SMS genes, SMS activity and the levels of the lipids regulated by SMS (namely sphingomyelin (SM) and DAG) are up-regulated during neutrophil differentiation. Finally, tissue imaging of lungs infected with C. neoformans using matrix-assisted laser desorption-ionization mass spectrometry (MALDI-MS), revealed that specific SM species are associated with neutrophil infiltration at the site of the infection. This study establishes a key role for SMS in the regulation of the killing activity of neutrophils against C. neoformans through a DAG-PKD dependent mechanism, and provides, for the first time, new insights into the protective role of host sphingolipids against a fungal infection

Topography-derived variables provide insight into habitat occupancy of a cryptic snake, Bitis atropos

Understanding species’ habitat use is fundamental for conservation and management. However, quantifying habitat use for small cryptic species is limited by imperfect detection during field surveys and the lack of habitat data at meaningful spatial scales. Topographically-derived habitat variables from digital elevation models (DEMs) have the potential to overcome these limitations. Here we used DEM-derived topographic variables as fine-scale proxies for abiotic conditions to study site-occupancy patterns of the berg adder (Bitis atropos), a small-bodied cryptic viper. We carried out seven repeated field surveys across 219 hectares in a mountainous protected area in north-eastern South Africa to estimate snake detection probability and occupancy using maximum likelihood methods. Although snakes occurred across a third of the surveyed habitat, they were only detected 40% of the time during the springtime when detection was highest. Results showed that these snakes preferred north-west facing, mid and upper slopes, which are exposed to afternoon sun and presumably higher ambient energy. Our results demonstrate the value of using DEM-derived topographic variables for ecological studies where habitat data are either unavailable or inappropriate, thereby providing valuable insights into habitat use of cryptic and difficult to detect species