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Healthy metabolic measures in humans are associated with longevity. Dysregulation leads to metabolic syndrome (MetS) and negative health outcomes. Recent exceptional longevity (EL) genome wide association studies have facilitated estimation of an individual's polygenic risk score (PRS) for EL. We tested the hypothesis that individuals with high ELPRS have a low prevalence of MetS. Participants were from five cohorts of middle-aged to older adults. The primary analyses were performed in the UK Biobank (UKBB) (n = 407,800, 40-69 years). Replication analyses were undertaken using three Australian studies: Hunter Community Study (n = 2122, 55-85 years), Older Australian Twins Study (n = 539, 65-90 years) and Sydney Memory and Ageing Study (n = 925, 70-90 years), as well as the Swedish Gothenburg H70 Birth Cohort Studies (n = 2273, 70-93 years). MetS was defined using established criteria. Regressions and meta-analyses were performed with the ELPRS and MetS and its components. Generally, MetS prevalence (22-30%) was higher in the older cohorts. In the UKBB, high EL polygenic risk was associated with lower MetS prevalence (OR = 0.94, p = 1.84 × 10-42) and its components (p < 2.30 × 10-8). Meta-analyses of the replication cohorts showed nominal associations with MetS (p = 0.028) and 3 MetS components (p < 0.05). This work suggests individuals with a high polygenic risk for EL have a healthy metabolic profile promoting longevity.

Perivascular space (PVS) burden is an emerging, poorly understood, magnetic resonance imaging marker of cerebral small vessel disease, a leading cause of stroke and dementia. Genome-wide association studies in up to 40,095 participants (18 population-based cohorts, 66.3 ± 8.6 yr, 96.9% European ancestry) revealed 24 genome-wide significant PVS risk loci, mainly in the white matter. These were associated with white matter PVS already in young adults (N = 1,748; 22.1 ± 2.3 yr) and were enriched in early-onset leukodystrophy genes and genes expressed in fetal brain endothelial cells, suggesting early-life mechanisms. In total, 53% of white matter PVS risk loci showed nominally significant associations (27% after multiple-testing correction) in a Japanese population-based cohort (N = 2,862; 68.3 ± 5.3 yr). Mendelian randomization supported causal associations of high blood pressure with basal ganglia and hippocampal PVS, and of basal ganglia PVS and hippocampal PVS with stroke, accounting for blood pressure. Our findings provide insight into the biology of PVS and cerebral small vessel disease, pointing to pathways involving extracellular matrix, membrane transport and developmental processes, and the potential for genetically informed prioritization of drug targets.

As autism is an invisible and often stigmatised condition, disclosing the diagnosis may lead to both support and/or discrimination. This mixed-methods questionnaire study examined autistic adults’ experiences of disclosure in various contexts. The sample consisted of 393 participants aged 17–83 years from two longitudinal surveys. Almost all participants disclosed their diagnosis to someone, most commonly to friends. A significant minority of participants studying and/or working at the time had not disclosed to their education provider/employer. Content analysis of open-ended responses showed participants desired to gain understanding and support from disclosure but feared prejudice. While some received support, others encountered dismissiveness and misunderstanding. Findings highlight the need to improve autism understanding and reduce stigma within and beyond educational and employment contexts.

Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging.

Carers of adults on the autism spectrum often experience high levels of stress, worry, and caregiver burden. There are few studies identifying the predictors of carer mental well-being and none have been conducted in Australia. Data from the Autism Cooperative Research Centre for Living with Autism’s Australian Longitudinal Study of Autism in Adulthood was used to test the conceptual model by Sonido et al. (Rev J Autism Dev Disord, 2019, https://doi.org/10.1007/s40489-019-00177-8) by (a) identifying the predictors of mental well-being for carers of adults on the spectrum, (b) using model selection to determine which predictors contribute to the model of best fit, and (c) testing for mediating relationships between the predictors. Several predictors were directly associated with carer psychological quality of life, including carer age, care recipient intellectual disability, and carer intolerance of uncertainty. Model selection strongly supported the inclusion of most clusters from the conceptual model. Some mediating relationships were found, such as care recipient depressive behaviours mediating the relationships between caregiver burden and psychological quality of life. Future studies of the conceptual model will improve understanding of the predictors of carer mental well-being and enable tailored interventions to improve the psychological health of carers of adults on the autism spectrum.

Ageing is associated with a decrease in odour identification. Additionally, deficits in olfaction have been linked to age-related disease and mortality. Heritability studies suggest genetic variation contributes to olfactory identification. The olfactory receptor (OR) gene family is the largest in the human genome and responsible for overall odour identification. In this study, we sought to find olfactory gene family variants associated with individual and overall odour identification and to examine the relationships between polygenic risk scores (PRS) for olfactory-related phenotypes and olfaction. Participants were Caucasian older adults from the Sydney Memory and Ageing Study and the Older Australian Twins Study with genome-wide genotyping data (n = 1395, mean age = 75.52 ± 6.45). The Brief-Smell Identification Test (BSIT) was administered in both cohorts. PRS were calculated from independent GWAS summary statistics for Alzheimer’s disease (AD), white matter hyperintensities (WMH), Parkinson’s disease (PD), hippocampal volume and smoking. Associations with olfactory receptor genes (n = 967), previously identified candidate olfaction-related SNPs (n = 36) and different PRS with BSIT scores (total and individual smells) were examined. All of the relationships were analysed using generalised linear mixed models (GLMM), adjusted for age and sex. Genes with suggestive evidence for odour identification were found for 8 of the 12 BSIT items. Thirteen out of 36 candidate SNPs previously identified from the literature were suggestively associated with several individual BSIT items but not total score. PRS for smoking, WMH and PD were negatively associated with chocolate identification. This is the first study to conduct genetic analyses with individual odorant identification, which found suggestive olfactory-related genes and genetic variants for multiple individual BSIT odours. Replication in independent and larger cohorts is needed.

Background: Studies of the representation of people with intellectual disability (ID) in custody report widely inconsistent findings that reflect variation in how ID is defined and the methods employed for identification. Using linked administrative data may be of utility in studies of the representation of people with ID in custody. However, this approach requires an understanding of the purpose of and factors influencing identification in disparate administrative datasets. Methods: This study uses linked administrative data encompassing disability, health and corrections data for the year 2014 to estimate the prevalence of ID in adult custody and explore how ID representation within administrative data impacts prevalence estimates and what patterns of identification reveal about support service access for this group. Results: This study finds that 4.3% of the New South Wales adult custody population had an identified ID. Prisoners with ID were younger, more likely to have had a previous custodial episode and more likely to be Indigenous than the general prison population. Identification of ID across linked administrative datasets is uneven, which, if used in isolation, would result in variation in prevalence estimates according to source data. Conclusions: The utilisation of linkage data from a broad range of health and support services including custody offers a comprehensive identification methodology. Inconsistency in the identification of ID across datasets indicates a potential disjuncture between prisoners with ID and support services, which may have relevance for efforts to reduce reincarceration of those in this population.

People with intellectual disability (ID) experience higher rates of mental illness and reduced access to appropriate care and treatment. Tailored electronic mental health (eMH) programs offer opportunities to address these disparities. The aim of this study is to examine whether a fully automated and self-guided eMH program tailored to the needs of people with ID can reduce symptoms of anxiety and depression and improve daily functioning in people with borderline-to-mild ID. Australians with borderline-to-mild ID, aged 16 years and older with mild-to-moderate depression and/or anxiety symptoms will be eligible to participate with the help of a nominated carer, if necessary. A randomised controlled trial with a sample size of 150 participants divided into treatment and waitlist control arms will be conducted. Participants randomised to the intervention group will have full access to the Healthy Mind program for eight weeks. The waitlist control group will gain full access to the program following the eight-week treatment period. Efficacy will be assessed on the Anxiety, Depression, and Mood Scale; Kessler-10; and the World Health Organisation Disability Assessment Schedule 2.0 across three time-points (baseline, eight weeks, and three months). We expect that people who use the intervention will report reduced depression and anxiety, relative to the control group. To our knowledge, this is the first study to examine the effectiveness of a fully automated eMH program for improving mental health in people with ID. We expect our study to render new knowledge on the delivery and effects of internet-based cognitive behaviour therapy (CBT) tools for people with ID.

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.

Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.

We aimed to examine the relationship between Apolipoprotein E ε4 (APOE*4) carriage on cognitive decline, and whether these associations were moderated by sex, baseline age, ethnicity, and vascular risk factors. Participants were 19,225 individuals aged 54–103 years from 15 longitudinal cohort studies with a mean follow-up duration ranging between 1.2 and 10.7 years. Two-step individual participant data meta-analysis was used to pool results of study-wise analyses predicting memory and general cognitive decline from carriage of one or two APOE*4 alleles, and moderation of these associations by age, sex, vascular risk factors, and ethnicity. Separate pooled estimates were calculated in both men and women who were younger (ie, 62 years) and older (ie, 80 years) at baseline. Results showed that APOE*4 carriage was related to faster general cognitive decline in women, and faster memory decline in men. A stronger dose-dependent effect was observed in older men, with faster general cognitive and memory decline in those carrying two versus one APOE*4 allele. Vascular risk factors were related to an increased effect of APOE*4 on memory decline in younger women, but a weaker effect of APOE*4 on general cognitive decline in older men. The relationship between APOE*4 carriage and memory decline was larger in older-aged Asians than Whites. In sum, APOE*4 is related to cognitive decline in men and women, although these effects are enhanced by age and carriage of two APOE*4 alleles in men, a higher numbers of vascular risk factors during the early stages of late adulthood in women, and Asian ethnicity.

Background Psychotropic medications are sometimes used off-label and inappropriately. This may cause harm to adolescents with intellectual disability. However, few studies have analysed off-label or inappropriate prescribing to this group. Aims To examine the appropriateness of psychotropic prescribing to adolescents with intellectual disability living in the community in south-east Queensland, Australia. Method Off-label medication use was determined based on whether the recorded medical condition treated was approved by the Australian Therapeutic Goods Administration. Clinical appropriateness of medication use was determined based on published guidelines and clinical opinion of two authors who specialise in developmental disability medicine (J.N.T. and D.H.). Results We followed 429 adolescents for a median of 4.2 years. A total of 107 participants (24.9%) were prescribed psychotropic medications on at least one occasion. Of these, 88 (82.2%) were prescribed their medication off-label or inappropriately at least once. Off-label or inappropriate use were most commonly associated with challenging behaviours. Conclusions Off-label or inappropriate use of psychotropic medications was common, especially for the management of challenging behaviours. Clinical decision-making accounts for individual patient factors and is made based on clinical experience as well as scientific evidence, whereas label indications are developed for regulatory purposes and, although appropriate at a population level, cannot encompass the foregoing considerations. Education for clinicians and other staff caring for people with intellectual disability, and a patient-centred approach to prescribing with involvement of families should encourage appropriate prescribing. The effect of the National Disability Insurance Scheme on the appropriateness of psychotropic medication prescribing should be investigated.

Background: People with intellectual disability (ID) have multiple and complex health needs, more frequent healthcare episodes, and experience poorer health outcomes. Research conducted two decades ago showed that medical professionals were lacking in the knowledge and skills required to address the complex needs of this patient group. The aim of the current study was to determine whether Australian undergraduate medical schools that offer ID health education content had changed the amount and nature of such teaching over this period. Methods: Identical or equivalent questionnaire items were compared across eight Australian medical schools that participated in curricula audits conducted in 1995 (referred to as T1) and 2013/14 (T2). The audits were of the nature of the ID content, methods used to teach it, and who taught it. Results: There was no significant difference in the number of hours of compulsory ID content offered to medical students at T2 (total = 158.3 h; median = 2.8 h per ID unit) compared with T1 (total = 171 h; median = 2.5 h). At T2 compared with T1, units with ID content taught in the area of general practice had increased (2 units; 3.6% to 7 units; 16.3%), while decreases were seen in paediatrics (22 units; 40.0% to 10 units; 23.3%) and psychiatry (10 units; 18.2% to 4 units; 9.3%). The number of schools using problem- and/or enquiry-based learning rose to six at T2 from one at T1. Inclusive teaching practices (people with ID develop or deliver content) in compulsory/elective units had increased at T2 (10 units; 23.3%) compared with T1 (6 units; 10.9%), but direct clinical contact with people with ID had decreased (29 units; 52.7% to 11 units; 25.6%). Conclusions: Overall, little progress has been made to address the gaps in ID education for medical students identified from an audit conducted in 1995. Renewal of ID content in medical curricula is indicated as a key element in efforts to improve workforce capacity in this area and reduce barriers to

Background: We examined how the relationship between education and latelife cognitive impairment (defined as a Mini Mental State Examination score below 24) is influenced by age, sex, ethnicity, and Apolipoprotein E epsilon 4 (APOE*4). Methods: Participants were 30,785 dementia-free individuals aged 55–103 years, from 18 longitudinal cohort studies, with an average follow-up ranging between 2 and 10 years. Pooled hazard ratios were obtained from multilevel parametric survival analyses predicting cognitive impairment (CI) from education and its interactions with baseline age, sex, APOE*4 and ethnicity. In separate models, education was treated as continuous (years) and categorical, with participants assigned to one of four education completion levels: Incomplete Elementary; Elementary; Middle; and High School. Results: Compared to Elementary, Middle (HR = 0.645, P = 0.004) and High School (HR = 0.472, P < 0.001) education were related to reduced CI risk. The decreased risk of CI associated with Middle education weakened with older baseline age (HR = 1.029, P = 0.056) and was stronger in women than men (HR = 1.309, P = 0.001). The association between High School and lowered CI risk, however, was not moderated by sex or baseline age, but was stronger in Asians than Whites (HR = 1.047, P = 0.044), and significant among Asian (HR = 0.34, P < 0.001) and Black (HR = 0.382, P = 0.016), but not White, APOE*4 carriers. Conclusion: High School completion may reduce risk of CI associated with advancing age and APOE*4. The observed ethnoregional differences in this effect are potentially due to variations in social, economic, and political outcomes associated with educational attainment, in combination with neurobiological and genetic differences, and warrant further study.

More adults are undergoing autism assessment due to recent changes in awareness, diagnostic criteria and professional practices. This scoping review aimed to summarise research on autism diagnosis in adulthood and identify any gaps for future study. The authors searched for studies involving first-time assessment and diagnosis of autism in adults, which identified 82 studies from 13 countries using various methodologies. Six themes of (1) prevalence, (2) diagnostic pathways and processes, (3) gender, (4) psychosocial characteristics, (5) co-occurring conditions and (6) experiences of diagnosis were identified across the studies. Findings suggest that receiving an autism diagnosis has a significant emotional impact on adults, but accessibility and processes are inconsistent, and formal support services are lacking. More research is needed on autism diagnosis in adults with intellectual disability, consequences of the timing of diagnosis, and support after diagnosis. Lay abstract: More adults are getting assessed for possible autism. Here, we give an overview on what is already known about autism diagnosis in adulthood and find areas that need more research. We divided results from the studies we found into six topics of (1) rates of autism in different groups; (2) the process of getting an autism diagnosis in adulthood; (3) gender; (4) personality traits, abilities and behaviours of diagnosed adults; (5) mental and physical health conditions that occur together with autism; and (6) how adults think and feel about being assessed and diagnosed. We found that adults often have strong emotions after being diagnosed, the process of getting a diagnosis can be unclear and different for everyone, and not many support services are available for adults. More research on diagnosing adults with intellectual disability, differences between early and late-diagnosed adults, and support after diagnosis would be useful.

Background: People with intellectual disability (ID) experience higher mortality than the general population. This study examines factors contributing to deaths in people with intellectual disability. Method: Linked administrative data spanning ten years for 49,947 people with intellectual disability receiving disability services were analysed to assess the impact of demographic variables, comorbidities and health service utilization on the risk of death using Cox proportional hazard models. Results: People admitted for cancer were 8 times more likely to die within the study period compared to people not admitted for cancer. Down syndrome, cerebral palsy and heart disease also increased the risk of death. Emergency department presentations and/or mental health admissions increased the risk of death 4 times. Conclusions: Our findings provide a basis for policy changes and public health interventions. Cancer screening, mental health interventions, inclusion of people with intellectual disability in health policy and improved health care are needed to meet the needs of this population.

There is a gap in our knowledge of aging with autism. The present study examined the applicability of the popular gerontology concept of “aging well” to autistic adults. Using survey data, a model of “aging well” was operationalised and applied to 92 autistic adults and 60 controls. A very small proportion (3.3%) of autistic adults were found to be aging well. Significantly less autistic adults were “maintaining physical and cognitive functioning” and “actively engaging with life” in comparison to controls. Whilst important differences in health and functioning status were found, the current dominant model of “aging well” is limited for examining autistic individuals. Suggested adjustments include development of a broader, more flexible and strengths -based model.

Introduction: Depression commonly accompanies Alzheimer's disease, but the nature of this association remains uncertain. Methods: Longitudinal data from the COSMIC consortium were harmonized for eight population-based cohorts from four continents. Incident dementia was diagnosed in 646 participants, with a median follow-up time of 5.6 years to diagnosis. The association between years to dementia diagnosis and successive depressive states was assessed using a mixed effect logistic regression model. A generic inverse variance method was used to group study results, construct forest plots, and generate heterogeneity statistics. Results: A common trajectory was observed showing an increase in the incidence of depression as the time to dementia diagnosis decreased despite cross-national variability in depression rates. Discussion: The results support the hypothesis that depression occurring in the preclinical phases of dementia is more likely to be attributable to dementia-related brain changes than environment or reverse causality.

Background: Can disability support services (DS) facilitate access to mental health services (MHS) for people with intellectual disability? This study utilized 10 years of data from 6,260 persons in NSW who had received DS and specific MHS to quantify the relationship between DS utilization and MHS utilization in adults with intellectual disability and co-existing mental illness. Results: Receipt of DS was associated with greater odds of accessing community mental health (CMH) services (36%, 95% CI 29%–43%) but not psychiatric admissions. Age, sex and social disadvantage did not affect the odds of psychiatric admission or CMH use. Individuals living in a remote area had greater odds of CMH use and lesser odds of psychiatric admission. Conclusions: Receipt of DS was associated with greater CMH but not psychiatric hospital utilization in people with intellectual disability and co-existing mental illness.

Autistic adults experience a higher rate of physical and mental health conditions and lower rates of employment and post-secondary education participation than their non-autistic counterparts, which may affect negatively quality of life. Limited information exists on predictors of quality of life for autistic individuals, or how quality of life compares to non-autistic individuals. Our aims were to (a) examine and compare indicators of physical (e.g. sleep quality) and mental health (e.g. anxiety) on quality of life among a sample of 244 autistic and 165 non-autistic individuals aged 15–80 years and (b) examine factors contributing to quality of life 2 years later among the autistic sample (n = 93). Participants were from two Australian longitudinal studies. The pattern of results for quality of life was similar across the autistic and non-autistic groups, with depression symptomatology, psychological well-being, sleep quality and autonomic symptoms all significantly predicting quality of life. In addition, among the autistic group, baseline quality of life had the greatest influence on quality of life 2 years later. These findings have implications for support services for autistic individuals, implying that in order to improve quality of life, mental health, particularly depression, needs addressing. Given known relationships between sleep and mental health, an intervention addressing these may have greatest clinical impact on quality of life among autistic individuals. Lay Abstract: Research shows that autistic adults are at risk of a range of physical (e.g. sleep difficulties) and mental health (e.g. anxiety) conditions, as well as lower employment and post-secondary education participation; these all can affect one’s quality of life. However, we have little information about what affects quality of life for autistic individuals across the lifespan and whether this differs from non-autistic people. We determined what factors (e.g. mental or physical health chall

We have carried out meta-analyses of genome-wide association studies (GWAS) (n = 23 784) of the first two principal components (PCs) that group together cortical regions with shared variance in their surface area. PC1 (global) captured variations of most regions, whereas PC2 (visual) was specific to the primary and secondary visual cortices. We identified a total of 18 (PC1) and 17 (PC2) independent loci, which were replicated in another 25 746 individuals. The loci of the global PC1 included those associated previously with intracranial volume and/or general cognitive function, such as MAPT and IGF2BP1. The loci of the visual PC2 included DAAM1, a key player in the planar-cell-polarity pathway. We then tested associations with occupational aptitudes and, as predicted, found that the global PC1 was associated with General Learning Ability, and the visual PC2 was associated with the Form Perception aptitude. These results suggest that interindividual variations in global and regional development of the human cerebral cortex (and its molecular architecture) cascade-albeit in a very limited manner-to behaviors as complex as the choice of one's occupation.

For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.

Objective: To describe the characteristics and clinical capacity of Australian and New Zealand psychiatrists working in intellectual and developmental disability mental health (IDDMH). Method: Consultant psychiatrists (n=71) with an interest or expertise in IDDMH completed an online survey about their roles, experience and time spent in intellectual developmental disability (IDD)-related activities. Results: Psychiatrists had worked in IDDMH for a median of 11.34 years and half (53.5%) reported expertise in the area. One-fifth of psychiatrists reported IDDMH as their main area of practice. The majority of respondents (85.1%) reported that they were working clinically with people with IDD. Respondents practicing clinically worked a median of 8 hours in clinical and 3 hours in non-clinical IDD-related work per week. Conclusions: Surveyed psychiatrists had considerable experience in IDDMH. However, their work in IDDMH represented a relatively small proportion of their overall work hours, and a minority of respondents were responsible for a large proportion of clinical work. Exploring ways to broaden capacity is crucial to ensuring the mental health needs of people with IDD are met.

Objectives: This study aimed to examine the training experiences of and determine capacity to train future Australian and New Zealand psychiatrists working in intellectual and developmental disability mental health. Methods: Australian and New Zealand psychiatrists with expertise or interest in intellectual and developmental disability mental health completed an online survey detailing their training pathway, support for subspecialty training and capacity to provide rotations in this area. Results: Psychiatrists (n=71) indicated the most common reasons they started practicing in intellectual and developmental disability mental health, and these included seeing people with intellectual or developmental disability in a service in which they worked, or personal experience with intellectual or developmental disability. Compared to those trained overseas, psychiatrists trained in Australia or New Zealand had lower ratings of the sufficiency of education received in intellectual and developmental disability mental health. Of the total respondents, 80% supported the development of subspecialty training. Augmentation of intellectual and developmental disability mental health content in the intermediate stage of training was also strongly supported. Participants identified 80 potential six-month training rotations in this area. Conclusions: Psychiatrists working in intellectual and developmental disability mental health strongly support enhancements to intellectual or developmental disability training, including the development of subspecialty training, and can identify potential training capacity if such subspecialty training was developed.

Fragile X-associated tremor ataxia syndrome is an inherited neurodegenerative disorder caused by premutation expansions (55–200 CGG repeats) of the FMR1 gene. There is accumulating evidence to suggest that early cognitive and brain imaging signs may be observed in some premutation carriers without motor signs of FXTAS, but few studies have examined the relationships between subcortical brain volumes and cognitive performance in this group. This study examined the relationships between caudate volume and select cognitive measures (executive function and information processing speed) in men at risk of developing FXTAS and controls with normal FMR1 alleles (<45 CGG repeats). The results showed that men with premutation alleles performed worse on measures of executive function and information processing speed, and had significantly reduced caudate volume, compared to controls. Smaller caudate volume in the premutation group was associated with slower processing speed. These findings provide preliminary evidence that early reductions in caudate volume may be associated with cognitive slowing in men with the premutation who do not present with cardinal motor signs of FXTAS. If confirmed in future studies with larger PM cohorts, these findings will have important implications for the identification of sensitive measures with potential utility for tracking cognitive decline.

Focused investigations regarding mortality rates, risk factors, and cause of death in autistic populations remain scarce. The present study used large linked datasets spanning 2001–2015 to report the rates and risk factors for mortality and cause of death in individuals on the autism spectrum (n = 35,929 age range 5–64) with and without concurrent intellectual disability (ID) in New South Wales, Australia. Mortality rates for those on the autism spectrum were 2.06 times that of the general population. Concurrent ID, epilepsy, mental health conditions, and chronic physical health conditions were associated with a higher risk of death for those on the spectrum, whereas demographic variables such as gender and socioeconomic status were not. A differing profile of top causes of death was found for autistic individuals relative to the general population, with “nervous system and sense disorders” and “injury and poisoning” being the top-ranked causes for those on the spectrum. The findings alert the need for health promotion and management of concurrent physical and mental health conditions for those on the autism spectrum. There is also a need for better identification, diagnosis, and documentation of older adults on the autism spectrum. Autism Research 2019, 12: 806–815. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary: Rates of death are higher for autistic individuals compared to the general population. There is higher risk of death for autistic individuals who have additional mental and physical health conditions. The leading causes of death for autistic individuals with and without ID are “nervous system and sense disorders”, which includes epilepsy and “injury and poisoning”, respectively. To minimize risk of death, it is important to manage the mental and physical health individuals on the autism spectrum and to better understand the circumstances surrounding preventable deaths for this population.

Background: Australian publicly funded mental health services play a significant role in the assessment and management of mental illness for people with intellectual disability. However, there is limited knowledge on their preparedness to meet the needs of this population. Method: Public mental health professionals (n=566) completed an online survey that explored their attitudes, confidence, and training needs in the area of intellectual disability mental health. Descriptive analyses were undertaken. Results: Participants agreed that people with intellectual disability have the right to receive good mental health care, and have the same access to their service. They viewed treating them as part of their role, but given the resources available it was not possible to provide comprehensive care. Participants reported low confidence in key clinical areas and insufficient training. Conclusions: A comprehensive workforce development strategy is required to facilitate the engagement and capacity of public mental health professionals in this area.

People with intellectual disabilities (ID) experience high rates of mental health problems, particularly during the period of transition to adulthood. It is therefore important that the transition from child- to adult-oriented health services for people with ID is well managed to ensure appropriate orientation to ongoing adult mental health care. The purpose of this paper is to summarise the impact and experience of transition to adult mental health care for people with ID and those who support them, as well as issues related to current policy and practice in this area. Several opportunities for improvement are identified in the broad areas of policy, service structure and organisation, research and workforce capacity. Enhancements in these areas will lead to improved outcomes for young people with ID transitioning from child- to adult-oriented mental health care.

Little research has been carried out on the physical health of people with autism spectrum disorder (ASD). From the studies conducted with both children and adults, few studies have moved beyond retrospective record analysis and survey and conducted health assessment. The majority of the studies are from the United States of America with a small number conducted in Europe. A scoping review was conducted to determine what is known of the physical health of adults with ASD and to identify research gaps. In addition to studies of adults, this review includes studies of children to determine possible health trajectories. From the findings, it can be stated with confidence that people with ASD have a high rate of comorbidity and increased risk for chronic disease.

Blood levels of growth differentiation factor-15 (GDF-15), also known as macrophage inhibitory cytokine-1 (MIC-1), have been associated with various pathological processes and diseases, including cardiovascular disease and cancer. Prior studies suggest genetic factors play a role in regulating blood MIC-1/GDF-15 concentration. In the current study, we conducted the largest genome-wide association study (GWAS) to date using a sample of ~5,400 community-based Caucasian participants, to determine the genetic variants associated with MIC-1/GDF-15 blood concentration. Conditional and joint (COJO), gene-based association, and gene-set enrichment analyses were also carried out to identify novel loci, genes, and pathways. Consistent with prior results, a locus on chromosome 19, which includes nine single nucleotide polymorphisms (SNPs) (top SNP, rs888663, p = 1.690 × 10-35), was significantly associated with blood MIC-1/GDF-15 concentration, and explained 21.47% of its variance. COJO analysis showed evidence for two independent signals within this locus. Gene-based analysis confirmed the chromosome 19 locus association and in addition, a putative locus on chromosome 1. Gene-set enrichment analyses showed that the"COPI-mediated anterograde transport" gene-set was associated with MIC-1/GDF15 blood concentration with marginal significance after FDR correction (p = 0.067). In conclusion, a locus on chromosome 19 was associated with MIC-1/GDF-15 blood concentration with genome-wide significance, with evidence for a new locus (chromosome 1). Future studies using independent cohorts are needed to confirm the observed associations especially for the chromosomes 1 locus, and to further investigate and identify the causal SNPs that contribute to MIC-1/GDF-15 levels.

Background: Despite experiencing higher rates of physical and mental health conditions compared with the general population, people with intellectual disability face inequitable access to healthcare services. Improving education of healthcare professionals is one way to reduce these inequalities. Objective: To determine how intellectual disability content is taught within Australian nursing schools. Design: A two-phase audit of Australian nursing curricula content was conducted using an interview and online survey. Setting: Nursing schools Australia-wide providing pre-registration courses. Participants: For Phase 1, course coordinators from 31 nursing schools completed an interview on course structure. Teaching staff from 15 schools in which intellectual disability content was identified completed an online survey for Phase 2. Methods: Methods used to teach intellectual disability content and who taught the content were audited using an online survey. Results: Across the 15 schools offering intellectual disability content, lectures were the most common teaching method (82% of units), followed by tutorials (59%), workshops (26%), then other methods (e.g. e-learning; 12%). Approximately three-quarters of intellectual disability teaching used some problem-and/or enquiry-based learning. Only one nursing school involved a person with intellectual disability in delivering teaching content. Six (19%) participating schools identified staff who specialise in intellectual disability, and seven (23%) identified staff with a declared interest in the area. Conclusion: While some nursing schools are using diverse methods to teach intellectual disability content, many are not; as a result, nursing students may miss out on acquiring the attributes which enable them to address the significant health inequalities faced by this group. A specific deficit was identified relating to inclusive teaching and clinical contact with people with intellectual disability.

Background: Individuals with intellectual disability experience higher rates of physical and mental health conditions compared with the general population, yet have inequitable access to health care services. Improving the workplace capacity of medical professionals to meet the needs of this population is one way to reduce barriers to care and improve health outcomes. Using diverse pedagogy appropriate to learning outcomes to teach medical students about intellectual disability is a necessary step in improving future workplace capacity. However, there is a lack of research into how, and by whom, medical students are taught about intellectual disability. The aim of this study was to investigate this through an audit of Australian medical school curricula. Methods: The Deans of Australian universities that provide accredited medical degrees (n = 20) were invited by email to participate in a two-phase audit of intellectual disability content in the curricula. Phase 1 (n = 14 schools) involved the Dean's delegate completing a telephone interview or questionnaire regarding medical course structure. If intellectual disability content was identified, a unit coordinator was invited to complete a survey regarding how this content was taught and by whom (Phase 2; n = 12 schools). Results: There was considerable variability across Australian medical schools regarding methods used to teach content about intellectual disability. Didactic teaching methods were most frequently used (62% of units included some form of lecture), but workshops and tutorials were reasonably well represented (34% of units contained one or both). Thirty-six percent of units included two or more teaching methods. Almost all schools (83%) used some problem- and/or enquiry-based learning. Educator backgrounds included medicine, nursing, and allied health. A majority of schools (n = 9, 75%) involved people with intellectual disability designing and teaching content, but the extent to which this occurred was

Objective: To describe the characteristics of psychiatrists working in the area of intellectual and developmental disability mental health (IDDMH) across Australia and New Zealand. Methods: A secondary analysis of data collected by the Royal Australian and New Zealand College of Psychiatrists 2014 workforce survey. Characteristics of the IDDMH workforce (n=146 psychiatrists) were compared with those of the broader psychiatry workforce (n=1050 psychiatrists). Results: The IDDMH workforce were more likely than the broader psychiatry workforce to be working across both the public and private health sectors, be engaged in outreach work, endorse specialty practice areas pertinent to IDDMH, treat younger patients and work more clinical hours per week. Part-time status and retirement plans of the IDDMH workforce matched those of the broader psychiatry workforce. Conclusions: While some elements of the IDDMH workforce profile suggest this workforce is tailored to the needs of the population, the potential shortage of IDDMH psychiatrists highlights the need for the development of a specific training programme and pathway in this area.

Autism spectrum disorder is associated with high rates of co-occurring health conditions. While elevated prescription rates of psychotropic medications have been reported in the United Kingdom and the United States, there is a paucity of research investigating clinical and prescribing practices in Australia. This study describes the problems managed and medications prescribed by general practitioners in Australia during encounters where an autism spectrum disorder was recorded. Information was collected from 2000 to 2014 as part of the Bettering the Evaluation and Care of Health programme. Encounters where patients were aged less than 25 years and autism spectrum disorder was recorded as one of the reasons for encounter and/or problems managed (n = 579) were compared to all other Bettering the Evaluation and Care of Health programme encounters with patients aged less than 25 years (n = 281,473). At ‘autism spectrum disorder’ encounters, there was a significantly higher management rate of psychological problems, and significantly lower management rates of skin, respiratory and general/unspecified problems, than at ‘non-autism spectrum disorder’ encounters. The rate of psychological medication prescription was significantly higher at ‘autism spectrum disorder’ encounters than at ‘non-autism spectrum disorder’ encounters. The most common medications prescribed at ‘autism spectrum disorder’ encounters were antipsychotics and antidepressants. Primary healthcare providers need adequate support and training to identify and manage physical and mental health concerns among individuals with autism spectrum disorder.

We used a sub-sample from the Older Australian Twins Study to estimate the heritability of performance on three tests of language ability: Boston Naming Test (BNT), Letter/Phonemic Fluency (FAS) and Category/Semantic Fluency (CFT) Tests. After adjusting for age, sex, education, mood, and global cognition (GC), heritability estimates obtained for the three tests were 0.35, 0.59, and 0.20, respectively. Multivariate analyses showed that the genetic correlation were high for BNT and CFT (0.61), but low for BNT and FAS (0.17), and for FAS and CFT (0.28). Genetic modelling with Cholesky decomposition indicated that the covariation between the three measures could be explained by a common genetic factor. Environmental correlations between the language ability measures were low, and there were considerable specific environmental influences for each measure. Future longitudinal studies with language performance and neuroimaging data can further our understanding of genetic and environmental factors involved in the process of cognitive aging.

General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.

© 2016 AMDA - The Society for Post-Acute and Long-Term Care Medicine.Background: The nature and commonality of late-life risk factors for mild cognitive impairment (MCI), dementia, and mortality remain unclear. Our aim was to investigate potential risk factors, simultaneously in a single cohort including many individuals initially with normal cognition and followed for 6 years. Methods: We classified 873 community-dwelling individuals (70-90 years old and without dementia at baseline) from the Sydney Memory and Ageing Study as cognitively normal (CN), having MCI or dementia, or deceased 6 years after baseline. Associations with baseline demographic, lifestyle, health, and medical factors were investigated, including apolipoprotein (APOE) genotype, MCI at baseline, and reversion from MCI to CN within 2 years of baseline. Results: Eighty-three (9.5%) participants developed dementia and 114 (13%) died within 6 years; nearly 33% had MCI at baseline, of whom 28% reverted to CN within 2 years. A core set of baseline factors was associated with MCI and dementia at 6 years, including older age (per year: odds ratios and 95% confidence intervals = 1.08, 1.01-1.14 for MCI; 1.19, 1.09-1.31 for dementia), MCI at baseline (5.75, 3.49-9.49; 8.23, 3.93-17.22), poorer smelling ability (per extra test point: 0.89, 0.79-1.02; 0.80, 0.68-0.94), slower walking speed (per second: 1.12, 1.00-1.25; 1.21, 1.05-1.39), and being an . APOE ε4 carrier (1.84, 1.07-3.14; 3.63, 1.68-7.82). All except . APOE genotype were also associated with mortality (age: 1.11, 1.03-1.20; MCI: 3.87, 1.97-7.59; smelling ability: 0.83, 0.70-0.97; walking speed: 1.18, 1.03-1.34). Compared with stable CN participants, individuals reverting from MCI to CN after 2 years were at greater risk of future MCI (3.06, 1.63-5.72). Those who reverted exhibited some different associations between baseline risk factors and 6-year outcomes than individuals with stable MCI. Conclusion: A core group of late-life risk factors indic

Recent evidence indicates that adults with a premutation (PM: 55–199 CGG repeats) expansion in the fragile X mental retardation 1 (FMR1) gene show postural control deficits that may reflect disruption to cerebellar motor regions. Less is known about the influence of reduced cerebellar volume and structural changes, and increase in CGG repeat and FMR1 mRNA levels on the attentional demands of step initiation in PM males. We investigated the effects of a concurrent cognitive task on choice stepping reaction time (CSRT) and explored the associations between CSRT performance, cerebellar volume, CGG size, and FMR1 mRNA levels in blood in PM males. We examined 19 PM males (ages 28–75) and 23 matched controls (CGG <44; ages 26–77), who performed a verbal fluency task during CSRT performance and single-task stepping without a secondary cognitive task. Our results provide preliminary evidence that smaller cerebellar volume (β = −2.73, p = 0.002) and increasing CGG repeat length (β = 1.69, p = 0.003) were associated with greater dual-task step initiation times in PM males, but not in controls. There was evidence of a mediating effect of cerebellar volume on the relationship between FMR1 mRNA levels and single-task CSRT performance in PM males (estimate coefficient = 8.69, standard error = 4.42, p = 0.049). These findings suggest increasing CGG repeat and FMR1 mRNA levels have neurotoxic effects on cerebellar regions underlying anticipatory postural responses during stepping. Cerebellar postural changes may be predictive of the increased risk of falls in older PM males.