Neuroimaging and other modalities to assess Alzheimer's disease in Down syndrome

People with Down syndrome (DS) develop Alzheimer's disease (AD) at higher rates and a younger age of onset compared to the general population. As the average lifespan of people with DS is increasing, AD is becoming an important health concern in this group. Neuroimaging is becoming an increasingly useful tool in understanding the pathogenesis of dementia development in relation to clinical symptoms. Furthermore, neuroimaging has the potential to play a role in AD diagnosis and monitoring of therapeutics. This review describes major recent findings from in vivo neuroimaging studies analysing DS and AD via ligand-based positron emission tomography (PET), [18F] fluorodeoxyglucose (FDG)-PET, structural magnetic resonance imaging (sMRI), and diffusion tensor imaging (DTI). Electroencephalography (EEG) and retinal imaging are also discussed as emerging modalities. The review is organized by neuroimaging method and assesses the relationship between cognitive decline and neuroimaging changes. We find that amyloid accumulation seen on PET occurs prior to dementia onset, possibly as a precursor to the atrophy and white matter changes seen in MRI studies. Future PET studies relating tau distribution to clinical symptoms will provide further insight into the role this protein plays in dementia development. Brain activity changes demonstrated by EEG and metabolic changes seen via FDG-PET may also follow predictable patterns that can help track dementia progression. Finally, newer approaches such as retinal imaging will hopefully overcome some of the limitations of neuroimaging and allow for detection of dementia at an earlier stage.This work was supported by a scholarship from the Clinical Neuroscience Training Program of Perelman School of Medicine to Natalie Neale

The Early Presentation of Dementia in People with Down Syndrome: a Systematic Review of Longitudinal Studies

Adults with Down syndrome (DS) are at a very high risk of developing early onset Alzheimer's disease (AD) due to trisomy of chromosome 21. AD is preceded by a prolonged prodromal "pre-clinical" phase presenting with clinical features that do not fulfil the diagnostic criteria for AD. It is important to clinically characterise this prodromal stage to help early detection of the disease as neuropathology of AD is almost universal by the fifth decade in DS. There is a lack of knowledge of the trajectory of decline associated with the onset of dementia in this population and early signs may be overlooked or misdiagnosed, negatively affecting the quality of life of those affected and the use of early pharmacological or psychosocial interventions. The objective of this systematic review is to evaluate the published literature on longitudinal data in order to identify the cognitive and behavioural changes occurring during the prodromal and early stages of AD in this population. Fifteen peer-reviewed articles met the inclusion criteria, including a total number of 831 participants, with the duration between baseline and follow up varying from 1 year to 47 years. Results suggest that, compared to the general population for which short-term (episodic) memory loss is the most common indicator associated with the onset of AD, in people with DS, executive dysfunction and Behavioural and Psychological Symptoms of Dementia (BPSD) are commonly observed during pre-clinical and early stages and may precede memory loss. The review highlights the importance of using a broad spectrum of assessments in the context of heterogeneity of symptoms. Theoretical and practical implications are discussed, as well as the need for further research.This systematic review is part of a larger research study funded by the Baily Thomas Charitable Fund, Addenbrookes Charitable Trust and the Health Foundation. Queens’ College Cambridge contributed via a grant which enabled the dissemination of these findings at BNA 2015 Festival of Neuroscience in Edinburgh

Art Installation as a Catalyst to Activities and Positive Behaviour in Back Lanes of Shah Alam Commercial Areas

This paper represents on women behavior safety enigma, also an on-going progress study of the cultural landscape in the context of the historic city where knowledge unfolds. The study has tracked women’s experience of place, which responses on the visual elements that become an incredibly diverse culture surrounding and norms. Eventually, the historic city seems meet their expectations in cultural aspects a safe building has resulted for living and work environment. Therefore, having known their understanding influence on structure-building façade concluded and rediscovered the perception that adds value contributes in the urban setting.© 2016. The Authors. Published for AMER ABRA by e-International Publishing House, Ltd., UK. Peer–review under responsibility of AMER (Association of Malaysian Environment-Behaviour Researchers), ABRA (Association of Behavioural Researchers on Asians) and cE-Bs (Centre for Environment-Behaviour Studies, Faculty of Architecture, Planning & Surveying, Universiti Teknologi MARA, Malaysia.Keywords: People and environments; cultural knowledge; architecture; indigenous architectur

Optimizing the lateral beamforming step for filtered-delay multiply and sum beamforming to improve active contour segmentation using ultrafast ultrasound imaging

As an alternative to delay-and-sum beamforming, a novel beamforming technique called filtered-delay multiply and sum (FDMAS) was introduced recently to improve ultrasound B-mode image quality. Although a considerable amount of work has been performed to evaluate FDMAS performance, no study has yet focused on the beamforming step size, , in the lateral direction. Accordingly, the performance of FDMAS was evaluated in this study by fine-tuning to find its optimal value and improve boundary definition when balloon snake active contour (BSAC) segmentation was applied to a B-mode image in ultrafast imaging. To demonstrate the effect of altering in the lateral direction on FDMAS, measurements were performed on point targets, a tissue-mimicking phantom and in vivo carotid artery, by using the ultrasound array research platform II equipped with one 128-element linear array transducer, which was excited by 2-cycle sinusoidal signals. With 9-angle compounding, results showed that the lateral resolution (LR) of the point target was improved by 67.9% and 81.2%, when measured at −6 dB and −20 dB respectively, when was reduced from to . Meanwhile the image contrast ratio (CR) measured on the CIRS phantom was improved by 10.38 dB at the same reduction and the same number of compounding angles. The enhanced FDMAS results with lower side lobes and less clutter noise in the anechoic regions provides a means to improve boundary definition on a B-mode image when BSAC segmentation is applied

The Down syndrome brain in the presence and absence of fibrillar β-amyloidosis

People with Down syndrome (DS) have a neurodevelopmentally distinct brain and invariably developed amyloid neuropathology by age 50. This cross-sectional study aimed to provide a detailed account of DS brain morphology and the changes occuring with amyloid neuropathology. Forty-six adults with DS underwent structural and amyloid imaging-the latter using Pittsburgh compound B (PIB) to stratify the cohort into PIB-positive (n = 19) and PIB-negative (n = 27). Age-matched controls (n = 30) underwent structural imaging. Group differences in deep gray matter volumetry and cortical thickness were studied. PIB-negative people with DS have neurodevelopmentally atypical brain, characterized by disproportionately thicker frontal and occipitoparietal cortex and thinner motor cortex and temporal pole with larger putamina and smaller hippocampi than controls. In the presence of amyloid neuropathology, the DS brains demonstrated a strikingly similar pattern of posterior dominant cortical thinning and subcortical atrophy in the hippocampus, thalamus, and striatum, to that observed in non-DS Alzheimer's disease. Care must be taken to avoid underestimating amyloid-associated morphologic changes in DS due to disproportionate size of some subcortical structures and thickness of the cortex.This work was supported by the Medical Research Council (grant number: 98480 ). Additional support was received from the NIHR Cambridge Biomedical Research Centre, the NIHR Collaborations in Leadership for Applied Health Research and Care (CLAHRC) for the East of England, the NIHR Cambridge Dementia Biomedical Research Unit, the Down Syndrome Association and the Health Foundation

A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association studies (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of 185 thousand CAD cases and controls, interrogating 6.7 million common (MAF>0.05) as well as 2.7 million low frequency (0.005<MAF<0.05) variants. In addition to confirmation of most known CAD loci, we identified 10 novel loci, eight additive and two recessive, that contain candidate genes that newly implicate biological processes in vessel walls. We observed intra-locus allelic heterogeneity but little evidence of low frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect siz