Using health check data to understand risks for dementia and cognitive impairment among Torres Strait Islander and Aboriginal peoples in northern Queensland—a data linkage study

Objective: High rates of dementia are evident in First Nations populations, and modifiable risk factors may be contributing to this increased risk. This study aimed to use a longitudinal dataset to gain insights into the long-term risk and protective factors for dementia and cognitive impairment not dementia (CIND) in a Torres Strait Islander and Aboriginal population in Far North Queensland, Australia. Study Design and Setting: Probabilistic data linkage was used to combine baseline health check data obtained in 1998/2000 and 2006/2007 for 64 residents in remote communities with their results on a single dementia assessment 10–20 years later (2015–2018). The relationship between earlier measures and later CIND/dementia status was examined using generalized linear modeling with risk ratios (RRs). Due to the small sample size, bootstrapping was used to inform variable selection during multivariable modeling. Results: One third of participants (n = 21, 32.8%) were diagnosed with dementia (n = 6) or CIND (n = 15) at follow-up. Secondary school or further education (RR = 0.38, 95% CI 0.19–0.76, p = 0.006) and adequate levels of self-reported physical activity (RR = 0.26, 95% CI 0.13–0.52, p < 0.001) were repeatedly selected in bootstrapping and showed some evidence of protection against later CIND/dementia in final multivariate models, although these had moderate collinearity. Vascular risk measures showed inconclusive or unexpected associations with later CIND/dementia risk. Conclusions: The preliminary findings from this small study highlighted two potential protective factors for dementia that may be present in this population. A tentative risk profile for later CIND/dementia risk is suggested, although the small sample size limits the applicability of these findings

Using health check data to investigate cognitive function in Aboriginal and Torres Strait Islanders living with diabetes in the Torres Strait, Australia

Background: Type 2 Diabetes (T2DM) has a subtle deleterious effect on cognition and imposes a higher lifetime risk of cognitive impairment and dementia. In populations where both T2DM and dementia are highly prevalent, understanding more about the early effects of T2DM on cognition may provide insights into the lifetime risks of this disease. Methods: In 2016, 186 Australian Aboriginal and/or Torres Strait Islander residents of the Torres Strait (54% female, mean age =8.9 years, SD =15.9, range =15–74) participated in a community health check. The effect of diabetes (Type 1 or Type 2) on speed of thinking and working memory was assessed with the Cogstate Brief Battery (CBB) during the health check. Results: One third of participants had diabetes (n = 56, 30.1%). After adjusting for age, education and previous iPad/Tablet experience, participants with diabetes had a small, yet significant reduction in accuracy on the One Back working memory task (β = −.076, p =.010, r2 =.042). The effect was most pronounced among participants with diabetes aged 20–49 years (n = 20), who also had evidence of poorer diabetes control (eg HbA1c% ≥6.5, 76.6%), relative to participants with diabetes aged 50 years and over (n = 31) (HbA1c% ≥6.5, 32.0%, p =.005). Conclusions: Early and subtle decrements in working memory may be a potential complication of diabetes among Aboriginal and Torres Strait Islander residents of the Torres Strait. Several potentially influential variables were not captured in this study (eg medication and diabetes duration). Greater preventative health resources are required for this population, particularly given the emerging elevated dementia rates linked to chronic disease

Compartmentalized PDE4A5 signaling impairs hippocampal synaptic plasticity and long-term memory

Alterations in cAMP signaling are thought to contribute to neurocognitive and neuropsychiatric disorders. Members of the cAMP-specific phosphodiesterase 4 (PDE4) family, which contains &gt;25 different isoforms, play a key role in determining spatial cAMP degradation so as to orchestrate compartmentalized cAMP signaling in cells. Each isoform binds to a different set of protein complexes through its unique N-terminal domain, thereby leading to targeted degradation of cAMP in specific intracellular compartments. However, the functional role of specific compartmentalized PDE4 isoforms has not been examined in vivo. Here, we show that increasing protein levels of the PDE4A5 isoform in mouse hippocampal excitatory neurons impairs a long-lasting form of hippocampal synaptic plasticity and attenuates hippocampus-dependent long-term memories without affecting anxiety. In contrast, viral expression of a truncated version of PDE4A5, which lacks the unique N-terminal targeting domain, does not affect long-term memory. Further, overexpression of the PDE4A1 isoform, which targets a different subset of signalosomes, leaves memory undisturbed. Fluorescence resonance energy transfer sensor-based cAMP measurements reveal that the full-length PDE4A5, in contrast to the truncated form, hampers forskolin-mediated increases in neuronal cAMP levels. Our study indicates that the unique N-terminal localization domain of PDE4A5 is essential for the targeting of specific cAMP-dependent signaling underlying synaptic plasticity and memory. The development of compounds to disrupt the compartmentalization of individual PDE4 isoforms by targeting their unique N-terminal domains may provide a fruitful approach to prevent cognitive deficits in neuropsychiatric and neurocognitive disorders that are associated with alterations in cAMP signaling

Dementia Risk Models in an Australian First Nations Population: Cross-Sectional Associations and Preparation for Follow-Up

Background: Reducing the burden of dementia in First Nations populations may be addressed through developing population specific methods to quantify future risk of dementia. Objective: To adapt existing dementia risk models to cross-sectional dementia prevalence data from a First Nations population in the Torres Strait region of Australia in preparation for follow-up of participants. To explore the diagnostic utility of these dementia risk models at detecting dementia. Methods: A literature review to identify existing externally validated dementia risk models. Adapting these models to cross-sectional data and assessing their diagnostic utility through area under the receiver operating characteristic curve (AUROC) analyses and calibration using Hosmer-Lemeshow Chi2. Results: Seven risk models could be adapted to the study data. The Aging, Cognition and Dementia (AgeCoDe) study, the Framingham Heart Study (FHS), and the Brief Dementia Screening Indicator (BDSI) had moderate diagnostic utility in identifying dementia (i.e., AUROC >0.70) before and after points for older age were removed. Conclusion: Seven existing dementia risk models could be adapted to this First Nations population, and three had some cross-sectional diagnostic utility. These models were designed to predict dementia incidence, so their applicability to identify prevalent cases would be limited. The risk scores derived in this study may have prognostic utility as participants are followed up over time. In the interim, this study highlights considerations when transporting and developing dementia risk models for First Nations populations

Potentially preventable dementia in a First Nations population in the Torres Strait and Northern Peninsula Area of North Queensland, Australia: A cross sectional analysis using population attributable fractions

Dementia is highly prevalent among Australia's First Nations peoples, including Torres Strait Islander and Aboriginal peoples in Far North Queensland (FNQ). It is likely that historically recent exposure to modifiable risk factors underlies these rates, and a large proportion of dementia may be potentially preventable. Data from two adult community health checks (2015-2018) were analyzed to determine the prevalence of 11 modifiable dementia risk factors among the First Nations residents of the Torres Strait and Northern Peninsula Area of FNQ. Population attributable fractions (PAF%) for dementia were calculated using age-standardized prevalence estimates derived from these health checks and relative risks obtained from previous meta-analyses in other populations. PAF% estimates were weighted for communality to account for overlap of risk factors. Half (52·1%) of the dementia burden in this population may be attributed to 11 potentially modifiable risk factors. Hypertension (9·4%), diabetes mellitus (9·0%), obesity (8·0%), and smoking (5·3%) were the highest contributing risk factors. The contribution of depression (2·0%) and alcohol (0·3%) was lower than other global and national estimates. While the adjusted PAF% for social isolation was low based on the adult community health check data (1·6%), it was higher (4·2%) when official census data were analyzed. These results suggest that a substantial proportion of dementia in FNQ First Nations peoples could potentially be prevented. Government investment in preventative health now is essential to reduce the future burden of dementia

Potentially modifiable dementia risk factors in all Australians and within population groups: an analysis using cross-sectional survey data

Background: Dementia is the second leading cause of disease burden in Australia. We aimed to calculate the population attributable fractions (PAFs) of dementia attributable to 11 of 12 previously identified potentially modifiable health and social risk factors (less education, hearing loss, hypertension, obesity, smoking, depression, social isolation, physical inactivity, diabetes, alcohol excess, air pollution, and traumatic brain injury), for Australians overall and three population groups (First Nations, and those of European and Asian ancestry). // Methods: We calculated the prevalence of dementia risk factors (excluding traumatic brain injury) and PAFs, adjusted for communality, from the cross-sectional National Aboriginal and Torres Strait Islander Health Survey (2018–19), National Aboriginal and Torres Strait Islander Social Survey (2014–15), National Health Survey (2017–18), and General Social Survey (2014) conducted by the Australian Bureau of Statistics. We conducted sensitivity analyses using proxy estimates for traumatic brain injury (12th known risk factor) for which national data were not available. // Findings: A large proportion (38·2%, 95% CI 37·2–39·2) of dementia in Australia was theoretically attributable to the 11 risk factors; 44·9% (43·1–46·7) for First Nations Australians, 36·4% (34·8–38·1) for European ancestry, and 33·6% (30·1–37·2) for Asian ancestry. Including traumatic brain injury increased the PAF to 40·6% (39·6–41·6) for all Australians. Physical inactivity (8·3%, 7·5–9·2), hearing loss (7·0%, 6·4–7·6), and obesity (6·6%, 6·0–7·3) accounted for approximately half of the total PAF estimates across Australia, and for all three population groups. // Interpretation: Our PAF estimates indicate a substantial proportion of dementia in Australia is potentially preventable, which is broadly consistent with global trends and results from other countries. The highest potential for dementia prevention was among First Nations Australians, reflecting the enduring effect of upstream social, political, environmental, and economic disadvantage, leading to greater life-course exposure to dementia risk factors. Although there were common dementia risk factors across different population groups, prevention strategies should be informed by community consultation and be culturally and linguistically appropriate. // Funding: Australian National Health and Medical Research Council and University College London Hospitals’ National Institute for Health Research (NIHR) Biomedical Research Centre, and North Thames NIHR Applied Research Collaboration

Primary care biomarkers and dementia in people of the Torres Strait, Australia: extended data analysis

Objective: Dementia disproportionately affects First Nations populations. Biomarkers collected in primary care may assist with determining dementia risk. Our previous underpowered study showed some suggestive associations between baseline biomarkers with follow-up dementia or cognitive impairment. The current study extended this work with a larger linked dataset. Study design and setting: Probabilistic data linkage was used to combine four baseline datasets with one follow-up assessment of dementia status 0–20 years later in a First Nations population in Australia. Mixed Effects Generalized Linear Regression models were used to test associations between baseline measures and follow-up status, accounting for repeated measures within individuals. Results: Linked data were available for 88 individuals, with 101–279 baseline observations, depending on the type of measure. Higher urinary albumin to creatine ratio was associated with greater risk of cognitive impairment/dementia, whereas body weight and key lipid markers were negatively associated. There was no clear trend when these associations were examined by timing of measurement (i.e., ≤10 years or >10 years before a dementia assessment). Conclusions: The results of this study support findings from our previous work and indicate that microalbuminuria can be an early indicator of dementia risk in this population. The weight and lipid profile findings reflect the mixed results in the published literature and require further investigation and interpretation

FNQ Connect: Connecting people, connecting care. A proposal for reform of disability, rehabilitation and lifestyle services for children, young people, adults and older people of FNQ

[Extract] FNQ Connect was created in response to a groundswell of interest and concern from FNQ people with lived experience of disability, their families and communities, together with stakeholders responsible for supporting them. They expressed an urgent need for service reform: current supply of services is outweighed by needs and is well below national standards; inaccuracies in national data conceal these inequities. Existing government, non-government and private services are largely fragmented; opportunities created by NDIS have added another layer of fragmentation. At the same time, demand for services is relentlessly increasing. To ensure quitable investment in services and continuity of care for the people of FNQ, accurate data and integration of services, were required

Accessing bacterial dark matter for improved enzyme discovery and engineering

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Biochemical adaptations of the retina and retinal pigment epithelium support a metabolic ecosystem in the vertebrate eye

Here we report multiple lines of evidence for a comprehensive model of energy metabolism in the vertebrate eye. Metabolic flux, locations of key enzymes, and our finding that glucose enters mouse and zebrafish retinas mostly through photoreceptors support a conceptually new model for retinal metabolism. In this model, glucose from the choroidal blood passes through the retinal pigment epithelium to the retina where photoreceptors convert it to lactate. Photoreceptors then export the lactate as fuel for the retinal pigment epithelium and for neighboring Mu ̈ ller glial cells. We used human retinal epithelial cells to show that lactate can suppress consumption of glucose by the retinal pigment epithelium. Suppression of glucose consumption in the retinal pigment epithelium can increase the amount of glucose that reaches the retina. This framework for understanding metabolic relationships in the vertebrate retina provides new insights into the underlying causes of retinal disease and age-related vision loss