Chemical Amelioration of Expansive Soils

Expansive soils swell when they absorb water and shrink when water evaporates from them. Hence, lightly loaded civil engineering structures found in these soils are subjected to severe distress. Therefore, there is a need to ameliorate or improve these swelling soils through some innovative methods. This paper discusses chemical stabilisation of expansive soils, a technique in which chemical reagents such as lime and calcium chloride are added to expansive soils to reduce the volumetric changes occurring in expansive soils and also to improve their engineering behaviour

Chemical Amelioration of Expansive Soils

Expansive soils swell when they absorb water and shrink when water evaporates from them. Hence, lightly loaded civil engineering structures found in these soils are subjected to severe distress. Therefore, there is a need to ameliorate or improve these swelling soils through some innovative methods. This paper discusses chemical stabilisation of expansive soils, a technique in which chemical reagents such as lime and calcium chloride are added to expansive soils to reduce the volumetric changes occurring in expansive soils and also to improve their engineering behaviour

Effect of apolipoprotein E polymorphism on cognition and brain in the Cambridge Centre for Ageing and Neuroscience cohort.

Polymorphisms in the apolipoprotein E (APOE) gene have been associated with individual differences in cognition, brain structure and brain function. For example, the ε4 allele has been associated with cognitive and brain impairment in old age and increased risk of dementia, while the ε2 allele has been claimed to be neuroprotective. According to the 'antagonistic pleiotropy' hypothesis, these polymorphisms have different effects across the lifespan, with ε4, for example, postulated to confer benefits on cognitive and brain functions earlier in life. In this stage 2 of the Registered Report - https://osf.io/bufc4, we report the results from the cognitive and brain measures in the Cambridge Centre for Ageing and Neuroscience cohort (www.cam-can.org). We investigated the antagonistic pleiotropy hypothesis by testing for allele-by-age interactions in approximately 600 people across the adult lifespan (18-88 years), on six outcome variables related to cognition, brain structure and brain function (namely, fluid intelligence, verbal memory, hippocampal grey-matter volume, mean diffusion within white matter and resting-state connectivity measured by both functional magnetic resonance imaging and magnetoencephalography). We found no evidence to support the antagonistic pleiotropy hypothesis. Indeed, Bayes factors supported the null hypothesis in all cases, except for the (linear) interaction between age and possession of the ε4 allele on fluid intelligence, for which the evidence for faster decline in older ages was ambiguous. Overall, these pre-registered analyses question the antagonistic pleiotropy of APOE polymorphisms, at least in healthy adults

Distinct resting-state functional connections associated with episodic and visuospatial memory in older adults.

Episodic and spatial memory are commonly impaired in ageing and Alzheimer's disease. Volumetric and task-based functional magnetic resonance imaging (fMRI) studies suggest a preferential involvement of the medial temporal lobe (MTL), particularly the hippocampus, in episodic and spatial memory processing. The present study examined how these two memory types were related in terms of their associated resting-state functional architecture. 3T multiband resting state fMRI scans from 497 participants (60-82 years old) of the cross-sectional Whitehall II Imaging sub-study were analysed using an unbiased, data-driven network-modelling technique (FSLNets). Factor analysis was performed on the cognitive battery; the Hopkins Verbal Learning test and Rey-Osterreith Complex Figure test factors were used to assess verbal and visuospatial memory respectively. We present a map of the macroscopic functional connectome for the Whitehall II Imaging sub-study, comprising 58 functionally distinct nodes clustered into five major resting-state networks. Within this map we identified distinct functional connections associated with verbal and visuospatial memory. Functional anticorrelation between the hippocampal formation and the frontal pole was significantly associated with better verbal memory in an age-dependent manner. In contrast, hippocampus-motor and parietal-motor functional connections were associated with visuospatial memory independently of age. These relationships were not driven by grey matter volume and were unique to the respective memory domain. Our findings provide new insights into current models of brain-behaviour interactions, and suggest that while both episodic and visuospatial memory engage MTL nodes of the default mode network, the two memory domains differ in terms of the associated functional connections between the MTL and other resting-state brain networks

5-HT₄ Receptor Agonist Effects on Functional Connectivity in the Human Brain:Implications for Procognitive Action

Background: Cognitive deficits are often comorbid with mood disorders and can cause significant functional impairment even after resolution of the primary mood symptoms. We do not currently have pharmacological treatments that adequately address these deficits. 5-HT4 receptor agonists show promise as potential procognitive agents in animal and early human translational studies. Optimal cognitive performance in humans is directly associated with appropriate functional connectivity between specific resting-state neural networks. However, so far the effect of 5-HT4 receptor agonism on resting-state functional connectivity (rsFC) in the brain in humans is unknown.Methods: We collected resting-state functional magnetic resonance imaging scans from 50 healthy volunteers, of whom 25 received 6 days × 1 mg prucalopride (a highly selective 5-HT4 receptor agonist) and 25 received placebo in a randomized double-blind design.Results: Network analyses identified that participants in the prucalopride group had enhanced rsFC between the central executive network and the posterior/anterior cingulate cortex. Seed analyses also showed greater rsFC between the left and right rostral anterior cingulate cortex and the left lateral occipital cortex, and reduced rsFC between the hippocampus and other default mode network regions.Conclusions: Similar to other potentially procognitive medications, low-dose prucalopride in healthy volunteers appeared to enhance rsFC between regions involved in cognitive networks and reduce rsFC within the default mode network. This suggests a mechanism for the behavioral cognitive enhancement previously seen with 5-HT4 receptor agonists in humans and supports the potential for 5-HT4 receptor agonists to be used in clinical psychiatric populations

Effect of age and the APOE gene on metabolite concentrations in the posterior cingulate cortex.

Proton magnetic resonance spectroscopy (1H-MRS) has provided valuable information about the neurochemical profile of Alzheimer's disease (AD). However, its clinical utility has been limited in part by the lack of consistent information on how metabolite concentrations vary in the normal aging brain and in carriers of apolipoprotein E (APOE) ε4, an established risk gene for AD. We quantified metabolites within an 8cm3 voxel within the posterior cingulate cortex (PCC)/precuneus in 30 younger (20-40 years) and 151 cognitively healthy older individuals (60-85 years). All 1H-MRS scans were performed at 3T using the short-echo SPECIAL sequence and analyzed with LCModel. The effect of APOE was assessed in a sub-set of 130 volunteers. Older participants had significantly higher myo-inositol and creatine, and significantly lower glutathione and glutamate than younger participants. There was no significant effect of APOE or an interaction between APOE and age on the metabolite profile. Our data suggest that creatine, a commonly used reference metabolite in 1H-MRS studies, does not remain stable across adulthood within this region and therefore may not be a suitable reference in studies involving a broad age-range. Increases in creatine and myo-inositol may reflect age-related glial proliferation; decreases in glutamate and glutathione suggest a decline in synaptic and antioxidant efficiency. Our findings inform longitudinal clinical studies by characterizing age-related metabolite changes in a non-clinical sample

Inter- and intra-individual variation in brain structural-cognition relationships in aging

The sources of inter- and intra-individual variability in age-related cognitive decline remain poorly understood. We examined the association between 20-year trajectories of cognitive decline and multimodal brain structure and morphology in older age. We used the Whitehall II Study, an extensively characterised cohort with 3T brain magnetic resonance images acquired at older age (mean age = 69.52 ± 4.9) and 5 repeated cognitive performance assessments between mid-life (mean age = 53.2 ±4.9 years) and late-life (mean age = 67.7 ± 4.9). Using non-negative matrix factorization, we identified 10 brain components integrating cortical thickness, surface area, fractional anisotropy, and mean and radial diffusivities. We observed two latent variables describing distinct brain-cognition associations. The first describes variations in 5 structural components associated with low mid-life performance across multiple cognitive domains, decline in reasoning, but maintenance of fluency abilities. The second describes variations in 6 structural components associated with low mid-life performance in fluency and memory, but retention of multiple abilities. Expression of latent variables predicts future cognition 3.2 years later (mean age = 70.87 ± 4.9). This data-driven approach highlights brain-cognition relationships wherein individuals degrees of cognitive decline and maintenance across diverse cognitive functions are both positively and negatively associated with markers of cortical structure

Classification and characterization of periventricular and deep white matter hyperintensities on MRI: A study in older adults.

White matter hyperintensities (WMH) are frequently divided into periventricular (PWMH) and deep (DWMH), and the two classes have been associated with different cognitive, microstructural, and clinical correlates. However, although this distinction is widely used in visual ratings scales, how to best anatomically define the two classes is still disputed. In fact, the methods used to define PWMH and DWMH vary significantly between studies, making results difficult to compare. The purpose of this study was twofold: first, to compare four current criteria used to define PWMH and DWMH in a cohort of healthy older adults (mean age: 69.58 ± 5.33 years) by quantifying possible differences in terms of estimated volumes; second, to explore associations between the two WMH sub-classes with cognition, tissue microstructure and cardiovascular risk factors, analysing the impact of different criteria on the specific associations. Our results suggest that the classification criterion used for the definition of PWMH and DWMH should not be considered a major obstacle for the comparison of different studies. We observed that higher PWMH load is associated with reduced cognitive function, higher mean arterial pressure and age. Higher DWMH load is associated with higher body mass index. PWMH have lower fractional anisotropy than DWMH, which also have more heterogeneous microstructure. These findings support the hypothesis that PWMH and DWMH are different entities and that their distinction can provide useful information about healthy and pathological aging processes

Development and validation of a dementia risk score in the UK Biobank and Whitehall II cohorts

BACKGROUND: Current dementia risk scores have had limited success in consistently identifying at-risk individuals across different ages and geographical locations. OBJECTIVE: We aimed to develop and validate a novel dementia risk score for a midlife UK population, using two cohorts: the UK Biobank, and UK Whitehall II study. METHODS: We divided the UK Biobank cohort into a training (n=176 611, 80%) and test sample (n=44 151, 20%) and used the Whitehall II cohort (n=2934) for external validation. We used the Cox LASSO regression to select the strongest predictors of incident dementia from 28 candidate predictors and then developed the risk score using competing risk regression. FINDINGS: Our risk score, termed the UK Biobank Dementia Risk Score (UKBDRS), consisted of age, education, parental history of dementia, material deprivation, a history of diabetes, stroke, depression, hypertension, high cholesterol, household occupancy, and sex. The score had a strong discrimination accuracy in the UK Biobank test sample (area under the curve (AUC) 0.8, 95% CI 0.78 to 0.82) and in the Whitehall cohort (AUC 0.77, 95% CI 0.72 to 0.81). The UKBDRS also significantly outperformed three other widely used dementia risk scores originally developed in cohorts in Australia (the Australian National University Alzheimer's Disease Risk Index), Finland (the Cardiovascular Risk Factors, Ageing, and Dementia score), and the UK (Dementia Risk Score). CLINICAL IMPLICATIONS: Our risk score represents an easy-to-use tool to identify individuals at risk for dementia in the UK. Further research is required to determine the validity of this score in other populations

Automated quality control for within and between studies diffusion MRI data using a non-parametric framework for movement and distortion correction

Diffusion MRI data can be affected by hardware and subject-related artefacts that can adversely affect downstream analyses. Therefore, automated quality control (QC) is of great importance, especially in large population studies where visual QC is not practical. In this work, we introduce an automated diffusion MRI QC framework for single subject and group studies. The QC is based on a comprehensive, non-parametric approach for movement and distortion correction: FSL EDDY, which allows us to extract a rich set of QC metrics that are both sensitive and specific to different types of artefacts. Two different tools are presented: QUAD (QUality Assessment for DMRI), for single subject QC and SQUAD (Study-wise QUality Assessment for DMRI), which is designed to enable group QC and facilitate cross- studies harmonisation efforts