Patterns of regional cerebellar atrophy in genetic frontotemporal dementia

BACKGROUND: Frontotemporal dementia (FTD) is a heterogeneous neurodegenerative disorder with a strong genetic component. The cerebellum has not traditionally been felt to be involved in FTD but recent research has suggested a potential role. METHODS: We investigated the volumetry of the cerebellum and its subregions in a cohort of 44 patients with genetic FTD (20 MAPT, 7 GRN, and 17 C9orf72 mutation carriers) compared with 18 cognitively normal controls. All groups were matched for age and gender. On volumetric T1-weighted magnetic resonance brain images we used an atlas propagation and label fusion strategy of the Diedrichsen cerebellar atlas to automatically extract subregions including the cerebellar lobules, the vermis and the deep nuclei. RESULTS: The global cerebellar volume was significantly smaller in C9orf72 carriers (mean (SD): 99989 (8939) mm(3)) compared with controls (108136 (7407) mm(3)). However, no significant differences were seen in the MAPT and GRN carriers compared with controls (104191 (6491) mm(3) and 107883 (6205) mm(3) respectively). Investigating the individual subregions, C9orf72 carriers had a significantly lower volume than controls in lobule VIIa-Crus I (15% smaller, p < 0.0005), whilst MAPT mutation carriers had a significantly lower vermal volume (10% smaller, p = 0.001) than controls. All cerebellar subregion volumes were preserved in GRN carriers compared with controls. CONCLUSION: There appears to be a differential pattern of cerebellar atrophy in the major genetic forms of FTD, being relatively spared in GRN, localized to the lobule VIIa-Crus I in the superior-posterior region of the cerebellum in C9orf72, the area connected via the thalamus to the prefrontal cortex and involved in cognitive function, and localized to the vermis in MAPT, the 'limbic cerebellum' involved in emotional processing

Detailed volumetric analysis of the hypothalamus in behavioral variant frontotemporal dementia

Abnormal eating behaviors are frequently reported in behavioral variant frontotemporal dementia (bvFTD). The hypothalamus is the regulatory center for feeding and satiety but its involvement in bvFTD has not been fully clarified, partly due to its difficult identification on MR images. We measured hypothalamic volume in 18 patients with bvFTD (including 9 MAPT and 6 C9orf72 mutation carriers) and 18 cognitively normal controls using a novel optimized multimodal segmentation protocol, combining 3D T1 and T2-weighted 3T MRIs (intrarater intraclass correlation coefficients ≥0.93). The whole hypothalamus was subsequently segmented into five subunits: the anterior (superior and inferior), tuberal (superior and inferior), and posterior regions. The presence of abnormal eating behavior was assessed with the revised version of the Cambridge Behavioural Inventory (CBI-R). The bvFTD group showed a 17 % lower hypothalamic volume compared with controls (p < 0.001): mean 783 (standard deviation 113) versus 944 (73) mm(3) (corrected for total intracranial volume). In the hypothalamic subunit analysis, the superior parts of the anterior and tuberal regions and the posterior region were significantly smaller in the bvFTD group compared with controls. There was a trend for a smaller hypothalamic volume, particularly in the superior tuberal region, in those with severe eating disturbance scores on the CBI-R. Differences were seen between the two genetic subgroups with significantly smaller volumes in the MAPT but not the C9orf72 group compared with controls. In summary, bvFTD patients had lower hypothalamic volumes compared with controls. Different genetic mutations may have a differential impact on the hypothalamus

Heritability of Lumbar Trabecular Bone Mechanical Properties in Baboons

Genetic effects on mechanical properties have been demonstrated in rodents, but not confirmed in primates. Our aim was to quantify the proportion of variation in vertebral trabecular bone mechanical properties that is due to the effects of genes. L3 vertebrae were collected from 110 females and 46 male baboons (6–32 years old) from a single extended pedigree. Cranio-caudally oriented trabecular bone cores were scanned with microCT then tested in monotonic compression to determine apparent ultimate stress, modulus, and toughness. Age and sex effects and heritability (h2) were assessed using maximum likelihood-based variance components methods. Additive effects of genes on residual trait variance were significant for ultimate stress (h2 = 0.58), toughness (h2 = 0.64), and BV/TV (h2 = 0.55). When BV/TV was accounted for, the residual variance in ultimate stress accounted for by the additive effects of genes was no longer significant. Toughness, however, showed evidence of a non-BV/TV-related genetic effect. Overall, maximum stress and modulus show strong genetic effects that are nearly entirely due to bone volume. Toughness shows strong genetic effects related to bone volume and shows additional genetic effects (accounting for 10% of the total trait variance) that are independent of bone volume. These results support continued use of bone volume as a focal trait to identify genes related to skeletal fragility, but also show that other focal traits related to toughness and variation in the organic component of bone matrix will enhance our ability to find additional genes that are particularly relevant to fatigue-related fractures

Publishing and sharing multi-dimensional image data with OMERO

Imaging data are used in the life and biomedical sciences to measure the molecular and structural composition and dynamics of cells, tissues, and organisms. Datasets range in size from megabytes to terabytes and usually contain a combination of binary pixel data and metadata that describe the acquisition process and any derived results. The OMERO image data management platform allows users to securely share image datasets according to specific permissions levels: data can be held privately, shared with a set of colleagues, or made available via a public URL. Users control access by assigning data to specific Groups with defined membership and access rights. OMERO’s Permission system supports simple data sharing in a lab, collaborative data analysis, and even teaching environments. OMERO software is open source and released by the OME Consortium at www.openmicroscopy.org

The implications of the United Nations Paris Agreement on climate change for globally significant biodiversity areas

Climate change is already affecting species and their distributions. Distributional range changes have occurred and are projected to intensify for many widespread plants and animals, creating associated risks to many ecosystems. Here, we estimate the climate change-related risks to the species in globally significant biodiversity conservation areas over a range of climate scenarios, assessing their value as climate refugia. In particular, we quantify the aggregated benefit of countries’ emission reduction pledges (Intended Nationally Determined Contributions and Nationally Determined Contributions under the Paris Agreement), and also of further constraining global warming to 2 °C above pre-industrial levels, against an unmitigated scenario of 4.5 °C warming. We also quantify the contribution that can be made by using smart spatial conservation planning to facilitate some levels of autonomous (i.e. natural) adaptation to climate change by dispersal. We find that without mitigation, on average 33% of each conservation area can act as climate refugium (or 18% if species are unable to disperse), whereas if warming is constrained to 2 °C, the average area of climate refuges doubles to 67% of each conservation area (or, without dispersal, more than doubles to 56% of each area). If the country pledges are fulfilled, an intermediate estimate of 47–52% (or 31–38%, without dispersal) is obtained. We conclude that the Nationally Determined Contributions alone have important but limited benefits for biodiversity conservation, with larger benefits accruing if warming is constrained to 2 °C. Greater benefits would result if warming was constrained to well below 2 °C as set out in the Paris Agreement

The prevalence and experience of oral diseases in Adelaide nursing home residents

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.Background: The twenty-first century will see the evolution of a population of dentate older Australians with dental needs very different from those of older adults in past years. This study provided comprehensive information concerning oral disease prevalence in older South Australian nursing home residents. Methods: This paper presents cross-sectional baseline results. Results: Most of the 224 residents, from seven randomly selected nursing homes, were functionally dependent, medically compromised, cognitively impaired and behaviourally difficult older adults who presented many complex challenges to carers and to dental professionals. Two-thirds (66 per cent) were edentulous with many dental problems and treatment needs. Dentate residents had a mean of 11.9 teeth present, higher than previously reported. The prevalence and experience of coronal and root caries and plaque accumulation was very high in dentate residents; especially males, those admitted more than three years previously, those who ate fewer food types and those who were severely cognitively impaired. These residents had more retained roots, decayed teeth and missing teeth, and fewer filled teeth when compared with data for community-dwelling older adults. Conclusions: This study highlighted the poor oral health status of these nursing home residents and the great impact of dementia on their high levels of oral diseases.JM Chalmers, C Hodge, JM Fuss, AJ Spencer, KD Carte

A neurogenetic model for the study of schizophrenia spectrum disorders: The International 22q11.2 Deletion Syndrome Brain Behavior Consortium

Rare copy number variants contribute significantly to the risk for schizophrenia, with the 22q11.2 locus consistently implicated. Individuals with the 22q11.2 deletion syndrome (22q11DS) have an estimated 25-fold increased risk for schizophrenia spectrum disorders, compared to individuals in the general population. The International 22q11DS Brain Behavior Consortium is examining this highly informative neurogenetic syndrome phenotypically and genomically. Here we detail the procedures of the effort to characterize the neuropsychiatric and neurobehavioral phenotypes associated with 22q11DS, focusing on schizophrenia and subthreshold expression of psychosis. The genomic approach includes a combination of whole genome sequencing and genome-wide microarray technologies, allowing the investigation of all possible DNA variation and gene pathways influencing the schizophrenia-relevant phenotypic expression. A phenotypically rich data set provides a psychiatrically well-characterized sample of unprecedented size (n=1,616) that informs the neurobehavioral developmental course of 22q11DS. This combined set of phenotypic and genomic data will enable hypothesis testing to elucidate the mechanisms underlying the pathogenesis of schizophrenia spectrum disorders