A commonly carried genetic variant in the delta opioid receptor gene, OPRD1, is associated with smaller regional brain volumes: Replication in elderly and young populations

Delta opioid receptors are implicated in a variety of psychiatric and neurological disorders. These receptors play a key role in the reinforcing properties of drugs of abuse, and polymorphisms in OPRD1 (the gene encoding delta opioid receptors) are associated with drug addiction. Delta opioid receptors are also involved in protecting neurons against hypoxic and ischemic stress. Here, we first examined a large sample of 738 elderly participants with neuroimaging and genetic data from the Alzheimer's Disease Neuroimaging Initiative. We hypothesized that common variants in OPRD1 would be associated with differences in brain structure, particularly in regions relevant to addictive and neurodegenerative disorders. One very common variant (rs678849) predicted differences in regional brain volumes. We replicated the association of this single-nucleotide polymorphism with regional tissue volumes in a large sample of young participants in the Queensland Twin Imaging study. Although the same allele was associated with reduced volumes in both cohorts, the brain regions affected differed between the two samples. In healthy elderly, exploratory analyses suggested that the genotype associated with reduced brain volumes in both cohorts may also predict cerebrospinal fluid levels of neurodegenerative biomarkers, but this requires confirmation. If opiate receptor genetic variants are related to individual differences in brain structure, genotyping of these variants may be helpful when designing clinical trials targeting delta opioid receptors to treat neurological disorders.

Automated ventricular mapping with multi-atlas fluid image alignment reveals genetic effects in Alzheimer's disease

We developed and validated a new method to create automated 3D parametric surface models of the lateral ventricles in brain MRI scans, providing an efficient approach to monitor degenerative disease in clinical studies and drug trials. First, we used a set of parameterized surfaces to represent the ventricles in four subjects' manually labeled brain MRI scans (atlases). We fluidly registered each atlas and mesh model to MRIs from 17 Alzheimer's disease (AD) patients and 13 age- and gender-matched healthy elderly control subjects, and 18 asymptomatic ApoE4-carriers and 18 age- and gender-matched non-carriers. We examined genotyped healthy subjects with the goal of detecting subtle effects of a gene that confers heightened risk for Alzheimer's disease. We averaged the meshes extracted for each 3D MR data set, and combined the automated segmentations with a radial mapping approach to localize ventricular shape differences in patients. Validation experiments comparing automated and expert manual segmentations showed that (1) the Hausdorff labeling error rapidly decreased, and (2) the power to detect disease- and gene-related alterations improved, as the number of atlases, N, was increased from 1 to 9. In surface-based statistical maps, we detected more widespread and intense anatomical deficits as we increased the number of atlases. We formulated a statistical stopping criterion to determine the optimal number of atlases to use. Healthy ApoE4-carriers and those with AD showed local ventricular abnormalities. This high-throughput method for morphometric studies further motivates the combination of genetic and neuroimaging strategies in predicting AD progression and treatment response. © 2007 Elsevier Inc. All rights reserved.

Automated 3D mapping & shape analysis of the lateral ventricles via fluid registration of multiple surface-based atlases

We developed and validated a new method to create automated 3D parametric surface models of the lateral ventricles, designed for monitoring degenerative disease effects in clinical neuroscience studies and drug trials. First we used a set of parameterized surfaces to represent the ventricles in a manually labeled set of 9 subjects' MRIs (atlases). We fluidly registered each of these atlases and mesh models to a set of MRIs from 12 Alzheimer's disease (AD) patients and 14 matched healthy elderly subjects, and we averaged the resulting meshes for each of these images. Validation experiments on expert segmentations showed that (1) the Hausdorff labeling error rapidly decreased, and (2) the power to detect disease-related alterations monotonically improved as the number of atlases, N, was increased from 1 to 9. We then combined the segmentations with a radial mapping approach to localize ventricular shape differences in patients. In surface-based statistical maps, we detected more widespread and intense anatomical deficits as we increased the number of atlases, and we formulated a statistical stopping criterion to determine the optimal value of N. Anterior horn anomalies in Alzheimer's patients were only detected with the multi-atlas segmentation, which clearly outperformed the standard single-atlas approach.

Diffusion indices on magnetic resonance imaging and neuropsychological performance in amnestic mild cognitive impairment

Background: Magnetic resonance diffusion tensor imaging (DTI) shows promise in the early detection of microstructural pathophysiological changes in the brain. Objectives: To measure microstructural differences in the brains of participants with amnestic mild cognitive impairment (MCI) compared with an age-matched control group using an optimised DTI technique with fully automated image analysis tools and to investigate the correlation between diffusivity measurements and neuropsychological performance scores across groups. Methods: 34 participants (17 participants with MCI, 17 healthy elderly adults) underwent magnetic resonance imaging (MRI)-based DTI. To control for the effects of anatomical variation, diffusion images of all participants were registered to standard anatomical space. Significant statistical differences in diffusivity measurements between the two groups were determined on a pixel-by-pixel basis using gaussian random field theory. Results: Significantly raised mean diffusivity measurements (p<0.001) were observed in the left and right entorhinal cortices (BA28), posterior occipital-parietal cortex (BA18 and BA19), right parietal supramarginal gyrus (BA40) and right frontal precentral gyri (BA4 and BA6) in participants with MCI. With respect to fractional anisotropy, participants with MCI had significantly reduced measurements (p<0.001) in the limbic parahippocampal subgyral white matter, right thalamus and left posterior cingulate. Pearson's correlation coefficients calculated across all participants showed significant correlations between neuropsychological assessment scores and regional measurements of mean diffusivity and fractional anisotropy. Conclusions: DTI-based diffusivity measures may offer a sensitive method of detecting subtle microstructural brain changes associated with preclinical Alzheimer's disease.

Corrigendum to "Mapping hippocampal and ventricular change in Alzheimer disease" [NeuroImage 22 (2004) 1754-1766] (DOI:10.1016/j.neuroimage.2004.03.040)

We recently noticed an error in the demographic data in this article. The validity of the findings and the conclusions of the paper is not affected. However, there is an error in the reported sample size and in the means and standard deviations of the subjects’ ages and MMSE scores. We would like to correct this error, which came to light when we were re-analyzing the data for a meta-analysis. The error occurred because an older version of a spreadsheet was incorrectly used when reporting the sample composition. Instead of examining 12 Alzheimer's disease patients and 14 healthy elderly controls, we in fact examined 17 Alzheimer’s disease patients and 14 healthy elderly controls. All maps and morphometric data reported in the paper are correct, except that the sample size was in fact slightly higher than that originally reported, and the maps computed in the paper were based on the larger sample (which included five more subjects in the Alzheimer’s disease group). All of the maps and figures in the paper are correct, and the conclusions of the paper are unchanged. We apologize for this error, which falls under the sole responsibility of the first author. The corrected demographic information appears below.

Malnutrition in the elderly : a narrative review

The focus of nutrition is often on healthy diets and exercise to minimise the risk of developing lifestyle diseases such as cancer, diabetes and cardiovascular disease. However, during the shift into older years often the nutrition priorities change towards meeting increased nutrient needs with less energy requirements and minimising lean muscle loss. There are several causes of general malnutrition in the elderly that lead to depletion of muscle including starvation (protein-energy malnutrition), sarcopenia and cachexia. The prevalence of protein-energy malnutrition increases with age and the number of comorbidities. A range of simple and validated screening tools can be used to identify malnutrition in older adults e.g. MST, MNA-SF and ‘MUST’. Older adults should be screened for nutritional issues at diagnosis, on admission to hospitals or care homes and during follow up at outpatient or General Practitioner clinics, at regular intervals depending on clinical status. Early identification and treatment of nutrition problems can lead to improved outcomes and better quality of life.

Genome-wide scan of healthy human connectome discovers SPON1 gene variant influencing dementia severity

Aberrant connectivity is implicated in many neurological and psychiatric disorders, including Alzheimer's disease and schizophrenia. However, other than a few disease-associated candidate genes, we know little about the degree to which genetics play a role in the brain networks; we know even less about specific genes that influence brain connections. Twin and family-based studies can generate estimates of overall genetic influences on a trait, but genome-wide association scans (GWASs) can screen the genome for specific variants influencing the brain or risk for disease. To identify the heritability of various brain connections, we scanned healthy young adult twins with high-field, highangular resolution diffusion MRI. We adapted GWASs to screen the brain's connectivity pattern, allowing us to discover genetic variants that affect the human brain's wiring. The association of connectivity with the SPON1 variant at rs2618516 on chromosome 11 (11p15.2) reached connectome-wide, genome-wide significance after stringent statistical corrections were enforced, and it was replicated in an independent subsample. rs2618516 was shown to affect brain structure in an elderly population with varying degrees of dementia. Older people who carried the connectivity variant had significantly milder clinical dementia scores and lower risk of Alzheimer's disease. As a posthoc analysis, we conducted GWASs on several organizational and topological network measures derived from the matrices to discover variants in and around genes associated with autism (MACROD2), development (NEDD4), and mental retardation (UBE2A) significantly associated with connectivity. Connectome-wide, genome-wide screening offers substantial promise to discover genes affecting brain connectivity and risk for brain diseases.

A comprehensive neuropsychiatric study of elderly twins: The Older Australian Twins Study

The Older Australian Twins Study (OATS) was recently initiated to investigate genetic and environmental factors and their associations and interactions in healthy brain ageing and ageing-related neurocognitive disorders. The study extends the classic MZ-DZ design to include one or two equivalently aged siblings for each twin pair and utilizes the rich resources of the Australian Twin Registry. The study has a number of distinguishing features including comprehensive psychiatric, neuropsychological, cardiovascular, metabolic, and neuroimaging assessments, a longitudinal design and links with a brain donor program. The study measures many behavioral and environmental factors, but in particular lifetime physical and mental activity, physical and psychological trauma, loss of parent early in life, later losses and life events, early-life socioeconomic environment, alcohol and drug use, occupational exposure, and nutrition. It also includes comprehensive cardiovascular assessment, blood biochemistry, genetics and proteomics. The socio-demographic and health data on the first 172 pairs of twins participating in this study are presented. Prevalence of mild cognitive impairment is 12.8% and of dementia 1.5% in the sample. The target sample size is 1000, with at least 400 pairs of twins aged 65-90 years. The cohort will be assessed every two years, with in-depth assessments being repeated. OATS offers an excellent opportunity for collaboration with other similar studies as well as researchers who share the same interests.

How to choose a healthy, eco-friendly childcare centre

The early years have been recognized as a “natural starting point” for education for sustainability. ECEfS is a newly emerging area and Australian educators, teacher educators, and researchers are leaders in this field. Indeed, there is a growing list of exemplary kindergartens, child care centres, preschools, and preps across the country engaged in EfS focusing on a range of topics that include, for example, water education, reducing energy use, recycling, growing gardens, and cleaning up parks and creeks. Some centres focus more on the social dimensions of sustainability – strengthening Indigenous communities, working with the elderly, supporting the unemployed, fostering gender equality in their communities, being more socially inclusive. There is mounting evidence that early lessons in sustainability help reshape adult sustainability actions in homes, schools and communities.

Smart buildings for healthy and sustainable workplace: scoping study report

Deficiencies in the design and operation of office buildings can give rise to high social, environmental and economic (triple bottom line) costs. As a result, there are significant pressures and incentives to develop ‘smart building’ technologies that can facilitate improved indoor environment quality (IEQ), and more energy efficient operation of office buildings. IEQ indicators include lighting, ventilation, thermal comfort, indoor air quality and noise. In response to this, the CRC for Construction Innovation commissioned a six-month scoping study (Project no. 2002-043) to examine how different technologies could be used to improve the ‘triple bottom line’ for office buildings. The study was supported by three industry partners, Bovis Lend Lease, Arup, and The Queensland Department of Public Works. The objective of the study was to look at the history, trends, drivers, new technologies and potential application areas related to the operation of healthy and efficient office buildings. The key output from the study was a recommendation for a prototype system for intelligent monitoring and control of an office environment, based on identified market, technical and user requirements and constraints.

Exercise alone is not enough : weight loss also needs a healthy (Mediterranean) diet?

Objective: In the majority of exercise intervention studies, the aggregate reported weight loss is often small. The efficacy of exercise as a weight loss tool remains in question. The aim of the present study was to investigate the variability in appetite and body weight when participants engaged in a supervised and monitored exercise programme. ---------- Design: Fifty-eight obese men and women (BMI = 31·8 ± 4·5 kg/m2) were prescribed exercise to expend approximately 2092 kJ (500 kcal) per session, five times a week at an intensity of 70 % maximum heart rate for 12 weeks under supervised conditions in the research unit. Body weight and composition, total daily energy intake and various health markers were measured at weeks 0, 4, 8 and 12. ---------- Results: Mean reduction in body weight (3·2 ± 1·98 kg) was significant (P < 0·001); however, there was large individual variability (−14·7 to +2·7 kg). This large variability could be largely attributed to the differences in energy intake over the 12-week intervention. Those participants who failed to lose meaningful weight increased their food intake and reduced intake of fruits and vegetables. ---------- Conclusion: These data have demonstrated that even when exercise energy expenditure is high, a healthy diet is still required for weight loss to occur in many people.

A comparison of the hazard perception ability of matched groups of healthy drivers aged 35 to 55, 65 to 74, and 75 to 84 years

We examined differences in response latencies obtained during a validated video-based hazard perception driving test between three healthy, community-dwelling groups: 22 mid-aged (35-55 years), 34 young-old (65-74 years), and 23 old-old (75-84 years) current drivers, matched for gender, education level, and vocabulary. We found no significant difference in performance between mid-aged and young-old groups, but the old-old group was significantly slower than the other two groups. The differences between the old-old group and the other groups combined were independently mediated by useful field of view (UFOV), contrast sensitivity, and simple reaction time measures. Given that hazard perception latency has been linked with increased crash risk, these results are consistent with the idea that increased crash risk in older adults could be a function of poorer hazard perception, though this decline does not appear to manifest until age 75+ in healthy drivers.

Elderly people's use of and attitudes towards assistive devices

People in developed countries are living longer with the help of medical advances. Literature has shown that older people prefer to stay independent and live at home for as long as possible. Therefore, it is important to find out how to best accommodate and assist them in maintaining quality of life and independence as well as easing human resources. Researchers have claimed that assistive devices assist in older people’s independence, however, only a small number of studies regarding the efficiency of assistive devices have been undertaken of which several have stated that devices are not being used. The overall aim of this research was to identify whether the disuse and ineffectiveness of assistive devices are related to change in abilities or related to the design of the devices. The objective was to gather information from the elderly; to identify what assistive devices are being used or not used and to gain an understanding on their attitudes towards assistive devices. Research was conducted in two phases. The initial phase of the research was conducted with the distribution of questionnaires to people over the age of fifty that asked general questions and specific questions on type of devices being used. Phase One was followed on by Phase Two, where participants from Phase One who had come in contact with assistive devices were invited to participate in a semi-structured interview. Questions were put forth to the interviewee on their use of and attitudes towards assistive devices. Findings indicated that the reasons for the disuse in assistive devices were mostly design related; bulkiness, reliability, performance of the device, difficulty of use. The other main reason for disuse was socially related; elderly people preferred to undertake activities on their own and only use a device as a precaution or when absolutely necessary. They would prefer not having to rely on the devices. Living situation and difference in gender did not affect the preference for the use of assistive devices over personal assistance. The majority strongly supported the idea of remaining independent for as long as possible. In conclusion, this study proposes that through these findings, product designers will have a better understanding of the requirements of an elderly user. This will enable the designers to produce assistive devices that are more practical, personalised, reliable, easy to use and tie in with the older people’s environments. Additional research with different variables is recommended to further justify these findings.

Healthy children, healthy planet : the case for transformative education in schools and early childhood from an Australian perspective

Climate change is an urgent global public health issue with substantial predicted impacts in the coming decades. Concurrently, global burden of disease studies highlight problems such as obesity, mental health problems and a range of other chronic diseases, many of which have origins in childhood. There is a unique opportunity to engage children in both health promotion and education for sustainability during their school years to help ameliorate both environmental and health issues. Evidence exists for the most effective ways to do this, through education that is empowering, action orientated and relevant to children’s day to day interests and concerns, and by tailoring such education to different educational sectors. The aim of this discussion paper is to argue the case for sustainability education in schools that links with health promotion and that adopts a practical approach to engaging children in these important public health and environmental issues. We describe two internationally implemented whole-school reform movements, Health Promoting Schools (HPS) and Sustainable Schools (SS) which seek to operationalise transformative educational processes. Drawing on international evidence and Australian case examples, we contend that children’s active involvement in such processes is not only educationally engaging and rewarding, it also contributes to human and environmental resilience and health. Further, school settings can play an important ecological public health role, incubating and amplifying the socially transformative changes urgently required to create pathways to healthy, just and sustainable human futures, on a viable planet.