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Background: Variability in cognitive decline among adults with Alzheimer's disease (AD) is seen across studies. While such variability is often modelled using linear models, in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study, application of a sigmoidal methodology has shown excellent precision in modelling cognitive and biomarker changes. Here we expand these findings by examining associations of brain volumes in AD specific Regions of Interest (ROIs) with accelerated cognitive decline among amyloid‐beta positive (Ab+) AIBL participants. Method: Longitudinal cognitive scores for the AIBL PACC, Language, Visuospatial functioning and CDR‐SB were mapped to sigmoidal trajectories, with a threshold defining the inflection point of accelerated cognitive decline. Participants to the left of the threshold were classified as having non‐accelerated decline (non‐accelerators), and participants beyond the threshold were classed as accelerators (Figure 1B). Using these classifications, we investigated differences in 16 ICV corrected ROI (left and right hemispheres pooled) for reductions in brain volume via generalised linear models adjusted for age, gender, and APOE‐e4 status. Three participant subgroups were tested: 1) Ab+/Tau unknown, 2) Ab+/Tau‐ and 3) Ab+/Tau+. Significant t‐values for the summed ROI volumes were mapped on a standard brain mesh for visualisation. Result: Of regions tested, two stood out consistently amongst top markers in each of the participant subgroups and cognitive outcomes: 1) supramarginal volume and 2) middle temporal volume (Figure 1C). Largest volume differences between accelerators and non‐accelerators were seen in the Ab+/Tau+ group; whilst smallest p‐values were in the Ab+/Tau unknown group due to a larger sample size (Table 1). Brain mesh visualization showed most of the AD signature ROIs altered in accelerator groups as compared with non‐accelerator groups. Figure 1D shows the AD signature for each cognitive outcome amongst the Ab+/Tau participant group. Top ranked ROI for the left being middle temporal volume (T=7.10, PACC) and supramarginal volume (T=7.10, CDR‐SB). Conclusion: Sigmoid analyses of MRI using binary cognitive scores show decreased ROI volumes in AIBL Ab+ participants with accelerated cognitive decline. This effect was mediated by known information on Tauopathy. Whilst effect sizes were high, smaller sample sizes in some groups affected p‐values and should therefore be replicated in larger samples. [ABSTRACT FROM AUTHOR]

Background: Human cytomegalovirus (HCMV) is a ubiquitous infectious agent, widely distributed in human populations. Its infection has been correlated with a number of age‐related disorders but associations with neurocognitive decline are not seen consistently. The Tumor Necrosis Factor‐α (TNF) is a cytokinine playing a key role in inflammation and TNF polymorphisms have been associated with various autoimmune diseases. In this study, we investigated the impact of TNF genotype and HCMV on age‐related cognitive decline. Method: The study cohort consisted of 200 Caucasian Australians (aged 59‐89 years) drawn from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. We used linear regression models to assess the effect of TNF genotype, HCMV and their interaction on a series of domain‐specific composite scores (Preclinical Alzheimer Cognitive Composite; PACC, Recognition, Attention Processing, Language). The models accounted for the potential effect of age, education level and Apolipoprotein E genotype. Result: The interaction between HCMV and TNF genotype significantly predicted PACC (b = 5.3; SE = 2.56; p = 0.04) and Recognition scores (b = 1.9; SE = 0.78; p = 0.01). Interactions were not significant in the other domains investigated (attention processing & language). Conclusion: The results suggest that the presence of TNF polymorphism, combined with HCMV infection have a protective effect against cognitive loss. Further research is needed to understand the underpinning mechanisms. [ABSTRACT FROM AUTHOR]

Modern microbial mats are highly complex and dynamic ecosystems. Diffusive equilibration in thin films ( DET) and diffusive gradients in thin films ( DGT) samplers were deployed in a modern smooth microbial mat from Shark Bay in order to observe, for the first time, two-dimensional distributions of porewater solutes during day and night time. Two-dimensional sulfide and alkalinity distributions revealed a strong spatial heterogeneity and a minor contribution of sulfide to alkalinity. Phosphate distributions were also very heterogeneous, while iron( II) distributions were quite similar during day and night with a few hotspots of mobilization. Lipid biomarkers from the three successive layers of the mat were also analysed in order to characterize the microbial communities regulating analyte distributions. The major hydrocarbon products detected in all layers included n-alkanes and isoprenoids, whilst other important biomarkers included hopanoids. Phospholipid fatty acid profiles revealed a decrease in cyanobacterial markers with depth, whereas sulfate-reducing bacteria markers increased in abundance in accordance with rising sulfide concentrations with depth. Despite the general depth trends in community structure and physiochemical conditions within the mat, two-dimensional solute distributions showed considerable small-scale lateral variability, indicating that the distributions and activities of the microbial communities regulating these solute distributions were equally heterogeneous and complex. [ABSTRACT FROM AUTHOR]

Background: The blood‐brain barrier (BBB) is formed by a high‐density lining of endothelial cells, providing a border between circulating blood and the brain interstitial fluid. This structure plays a key role in protecting the brain microenvironment by restricting passage of certain molecules and circulating pathogens. Method: This study aimed at identifying associations between longitudinal brain volumetric changes and a set of 324 BBB‐related single nucleotide polymorphisms (SNP), genotyped from 222 unrelated individuals (Ab+: N=95; Ab‐: N=127) enrolled in the Australian Imaging, Biomarker & Lifestyle (AIBL) study. We focused this research on four brain regions (cortical grey matter, cortical white matter, ventricular volume, and hippocampal volume) and used a linear mixed model approach to assess if specific genotypes were linked to rates of atrophy over a 12‐year time span. Results: We identified three genetic markers, specific to the Ab+ population, associated with accelerated volume change of the hippocampus and ventricular regions. Two markers, namely, rs17063341 (TJP2, flanking, p=1.35e‐05) and rs7975334 (SLCO1C1, non‐coding transcript variant, p=5.65e‐06) were associated with accelerated atrophy of the hippocampus. One marker, rs282984 (JAM2, intronic, p= 8.78e‐05) was linked to accelerated ventricular enlargement. These markers were independent of variation due to the APOE e4 allele and remained significant after correction for multiple comparisons. The identified associations were not seen in the Ab negative population. Conclusions: The results suggest that specific markers in key genes involved in the regulation of BBB integrity are associated with longitudinal changes of specific brain regions. Further research is required to validate these findings and investigate how BBB functions maybe compromised by these genetic variations. [ABSTRACT FROM AUTHOR]

Background: Grey matter atrophy occurs as a function of ageing and is accelerated in neurodegenerative conditions, such as dementia. Previous research suggests higher physical activity is associated with larger grey matter volumes; however, there appears to be individual variability in this association. Understanding factors that can affect the relationship between physical activity and brain volume will enable identification of individuals that gain the greatest neural benefits from physical activity. Method: Data from 10,084 men and women (aged 50+ years) of the UK Biobank were used to examine: 1) the relationship between actigraphy‐measured habitual physical activity and brain volume; and 2) whether the relationship between objectively‐measured physical activity and brain volume is moderated by age, sex, BDNF Val66Met, or APOE ε4 allele carriage. All participants underwent a magnetic resonance imaging scan to quantify grey matter volumes, activity monitoring, and genotyping. Result: Physical activity was associated with larger total grey matter volume (B = 0.14, p = 0.001) and right hippocampal volume (B = 1.45, p = 0.008). The physical activity*sex interaction was significant for cortical grey matter (B = 0.22, p = 0.003), total grey matter (B = 0.30, p < 0.001), and right hippocampal volume (B = 3.62, p = 0.001). A relationship between physical activity and brain volume was observed in males only (cortical grey matter volume, B= 0.13, p = 0.01; total grey matter volume, B=0.23, p < 0.001; and right hippocampal volume, B = 2.29, p = 0.008). No other moderating factors of the physical activity and brain volume relationship were identified. Conclusion: Our results indicate that in males, but not females, an association exists between habitual physical activity and brain volume. Future research should evaluate longitudinal brain volumetrics to better understand the nature of sex‐effects on the relationship between physical activity and brain volume. [ABSTRACT FROM AUTHOR]

Background: Neurodevelopmental genes and their associated protein products are involved in a number of biological processes essential for brain assembly. Despite their relative importance, the impact of genetic variation in neurodevelopmental genes on the neurodegenerative and neurocognitive changes that occur in Alzheimer's disease, is poorly characterised. Here, we investigated the associations between Single Nucleotide Polymorphisms (SNPs) in neurodevelopmental genes and brain volumetrics. Method: From a curated list of 40 genes related to neurodevelopmental processes, we identified a set of 233 independent SNPs. The genotype data was generated from 715 unrelated individuals (Amyloid Beta (Ab) ‐ N=328, Ab+ N=387), enrolled in the Australian Imaging, Biomarker & Lifestyle (AIBL) study. We focused this research on the cortical grey, subcortical white matter, ventricular, and hippocampal volumes and used linear mixed models to assess whether specific genotypes were associated to regional volume changes over time. The associations with the traits of interest were assessed cross‐sectionally at baseline and longitudinally, over a 12‐year time span. Result: At baseline, cross‐sectional analyses revealed one significant association between the variant, rs2923137, located in DRC7 (<20KB KATNB1) and ventricular volume (p = 2.13e‐4, β = 5.8). In the longitudinal analyses, we found that rs1142749, a marker located near TUBB4B, was consistently associated with accelerated rate of change in grey matter (p = 9.2e‐4, β = 0.034), hippocampal (p = 2.9e‐3, β = 0.025) and ventricular volume (p = 2.1e‐3, β = ‐0.028). Further, we observed that the strength and effects of these associations were exacerbated in Ab+ individuals but were absent in Ab negative sub‐population. Another noticeable link was identified between rs2555172 (DCHS1) and hippocampal volume change (p = 1.4e‐3, β = ‐0.024). The identified associations were independent of variation due to the APOE e4 allele and remained significant after correction for multiple comparisons. Conclusion: The results support the hypothesis that genes associated with neurodevelopmental processes and signalling mechanisms are relevant to Alzheimer's Disease. The identified associations suggest that mutations in key neurodevelopment genes could be linked to accelerated atrophy in specific areas of the brain. [ABSTRACT FROM AUTHOR]