Dementia Australia

BackgroundDementia is currently the second leading cause of death in Australia and the seventh leading cause of death worldwide. Diagnosis of Alzheimer's disease (AD), the major cause of dementia, is difficult and time consuming. Current clinical imaging technologies are costly to use for widespread early screening of AD and have limited availability. In contrast, the retina is unique, where blood vessels and neural tissue can be viewed and imaged non‐invasively and relatively inexpensively. As part of the central nervous system, the retina exhibits similarities to the brain and can display indicators of various neurological disorders, including AD. We aimed to image the retina and analyse its spectral features to develop a robust machine learning (ML) classification model that distinguishes between brain amyloid‐beta (Aβ) positive and negative individuals.MethodSixty‐eight consenting volunteers with varying levels of brain Aβ protein underwent non‐invasive imaging using a hyperspectral retinal camera and illumination of wavelengths from 450 to 905 nm. Multiple retina features from the central and superior views were selected and analysed to identify their variability among individuals with different brain amyloid loads. Eight ML models were evaluated for their performance in predicting brain Aβ levels using the retina images and systemic factors like age, gender and apolipoprotein E (APOE) genotype.ResultThe retinal reflectance spectra in the 405–585 nm wavelengths exhibited a significant difference in individuals with increasing brain amyloid. The retinal features in the superior view showed higher inter‐subject variability. Our comparison of eight different ML algorithms revealed that the Multi‐Layer Perceptron (MLP) model exhibited superior classification performance, achieving an accuracy of 0.86, precision of 0.88, recall of 0.82, F1‐score of 0.85, and area under curve (AUC) of 0.90.ConclusionThis study indicates that there are spectral variations of retinal features associated with brain amyloid loads. It also demonstrates the feasibility of the retinal hyperspectral imaging (rHSI) technique as a potential non‐invasive, inexpensive screening method to identify individuals in the preclinical phase of AD.

ABSTRACT Introduction Medicine-related harm associated with polypharmacy is a pertinent global health challenge. Deprescribing (reducing or stopping) medicines that cause more potential harm than benefit could mitigate the risk of medicine-related harm. However, the existing deprescribing research-to-practice gap threatens the long-term sustainability and scalability of deprescribing efforts. Research design and methods To address this, key stakeholders including healthcare practitioners, academics, policymakers and representatives of peak professional organizations, gathered at a World Café workshop to reflect on progress achieved in the deprescribing research and practice landscape while exploring the top future priorities for deprescribing. Results Thirty participants agreed on three top priorities: improving the clinical management of deprescribing; engaging consumers and gaining their perspectives; and raising awareness to enhance communication. Emerging themes and related barriers and catalysts were derived and mapped to a socio-ecological model offering a bird-eye’s view of these factors on an individual, interpersonal, organizational, and societal level. Conclusions Our World Cafe’ highlights opportunities for future deprescribing research and practice. To promote the uptake of deprescribing in practice, catalysts could include leveraging new technology, promoting deprescribing via social media and optimizing workforce staff and knowledge. Ultimately, this knowledge may motivate deprescribing efforts and bridge the research-to-practice gap.

BackgroundCSF and blood soluble TREM2 (sTREM2) levels have been found to increase at early stage of Alzheimer's disease (AD). The relationships between sTREM2, AD-related biomarkers, and other neuroinflammation biomarkers remain unclear. Moreover, the impact of rare variants in TREM2 gene (R47H/R62H), which are associated with increased risk of AD, on plasma sTREM2 has not been elucidated.ObjectiveInvestigate the association of plasma sTREM2 levels with brain amyloid-β (Aβ) load and AD-related blood biomarkers, i.e., phosphorylated tau (pTau)-181, pTau-231, GFAP, NFL, and other neuroinflammation and peripheral inflammation markers in cognitively normal (CN) older adults at risk of AD (CN Aβ+) compared to CN Aβ-, including the effect of AD-linked TREM2 rare variants.MethodsPlasma sTREM2 concentrations were measured by MesoScale Discovery (MSD) assay from the KARVIAH cohort. Participants underwent cognitive tests and PET amyloid imaging. Genetic data and blood biomarkers were included for correlation analysis. Associations with plasma sTREM2 were investigated upon stratification by PET-Aβ load SUVR ((CN Aβ- (n = 65) and CN Aβ+ (n = 35)) as the main analysis. A subgroup analysis based on the TREM2 R47H and R62H genotype was conducted as exploratory analysis.ResultsPlasma sTREM2 positively correlated with plasma pTau181, and pTau231 in CN Aβ+ group. Plasma sTREM2 positively correlated with serum microglial kynurenine pathway metabolites. Plasma sTREM2 and brain Aβ load were higher in R47H TREM2 carriers compared to non-carriers.ConclusionsOur findings suggest plasma sTREM2 relates to downstream tau processes in amyloid-positive individuals, providing novel insights into the roles of peripheral TREM2 signaling that reflects microglial activity in early AD neuropathological development.

BackgroundCurrently a definitive diagnosis for Alzheimer’s disease (AD) is not readily available to the wider community as the gold standard markers of AD are either invasive and/or expensive. Therefore, there is an urgent need for a relatively low‐cost blood test that can be readily used in clinical settings. This study aims to address this gap by developing a reliable and cost‐effective in‐house blood‐based biomarkers panel for routine use in clinical labs for early detection of AD. Our team have shown that specific proteins in the blood, namely phosphorylated tau and Glial Fibrillary Acidic Protein (GFAP) as biomarker for early AD diagnosis. However, only a combination of selected blood biomarkers can reliably predict who is at risk of AD. To achieve a combination diagnostic assay based on robust blood biomarkers, this study will first develop singleplex diagnostic Single Molecule Array (Simoa) blood biomarkers assays for phosphorylated Tau: p ‐Tau217 and pTau205, as well as the N‐ and C‐terminus of GFAP. A novel panel of the best 3 biomarkers will then be selected to establish a blood test for preclinical diagnosis of AD.MethodMonoclonal antibodies against p ‐Tau217, p ‐Tau205, N‐ and C‐terminus of GFAP were generated in collaboration with GenScript, Singapore. These antibodies have undergone initial characterisation with controlled primary assessment of specificity and affinity (i.e immunostaining, immunoprecipitation‐Western Blot, and immunoprecipitation‐mass spectrometry) using various tissues such as human cells expressing phospho‐site‐deficient tau as negative controls, human brain, CSF, and plasma from healthy controls and AD. Finally, these antibodies were developed for Simoa assay in collaboration with University of Gothenburg.ResultWe have successfully generated specific high affinity monoclonal antibodies against p ‐Tau217, p ‐Tau205, and N‐terminus GFAP and have confirmed that these antibodies have the necessary specificity and sensitivity for the Simoa platform.ConclusionThe development of Simoa assays will be validated in a highly characterised control and Alzheimer cohort The Australian Imaging, Biomarker, and Lifestyle (AIBL) and a novel panel of the best 3 biomarkers established.

BackgroundResearch has yielded advancements in understanding dementia and developing promising interventions. However, translating research findings into routine practice and policy remains a significant challenge. Additionally, there are few studies of implementation; that is, examination of the processes, outcomes, and factors influencing implementation of interventions. Implementation science provides a critical framework for addressing this gap by investigating factors that influence the adoption and sustainment of evidence‐based dementia care interventions in real‐world settings.MethodThis presentation provides an up‐to‐date overview of the evolving field of dementia implementation science, highlighting its role in improving care outcomes. The presenter outlines key theoretical frameworks and the core principles of implementation science, including identifying and addressing barriers to implementation, developing and testing implementation strategies, and evaluating the effectiveness of these strategies. This presentation uses as an example an applied research example from Australia – the Promoting Independence Through quality dementia Care in The Home (PITCH) study, aimed to improve sense of competency in dementia home care and outcomes for people with dementia via a co‐designed evidence‐based dementia training program.ResultA national cluster stepped‐wedge randomized controlled trial tested PITCH, alongside a health economic and process evaluation. Overall, the interactive, adult‐learning‐based, face‐to‐face PITCH program was effective in improving sense of competence in dementia care as well as knowledge and attitudes. For carers and people with dementia, no differences in health and quality of life outcomes were found. The process evaluation explored barriers and facilitators to implementation of PITCH, explored its acceptability, feasibility, suitability, and sustainability, and whether participation led to changes in practice. Themes from the process evaluation (from qualitative interviews and surveys) investigating the experiences and opinions of the intervention receivers and intervention deliverers included their motivations to participate, perceived benefits of PITCH, challenges of involvement, and suggestions for improvement, analyzed using the Theoretical Domains Framework. Results inform how the PITCH intervention could be modified to improve future wider implementation.ConclusionBy applying rigorous methodologies, the field of implementation science offers a promising avenue for maximizing the impact of dementia research and enhancing the quality of life for individuals living with dementia and their caregivers.

INTRODUCTIONFor a blood‐based biomarker to be considered a confirmatory test for the detection of abnormal amyloid beta (Aβ) levels, the sensitivity and specificity must be equivalent to that of current cerebrospinal fluid tests.METHODSIn the current study we assessed the ability of phosphorylated tau (p‐tau)217 and Aβ42/40 from the Lumipulse G p‐tau217 and β‐amyloid ratio (1‐42/1‐40) tests, individually and combined, to predict Aβ positron emission tomography status in two sub‐cohorts from the Australian Imaging, Biomarkers, and Lifestyle Study of Ageing.RESULTSTesting an Alzheimer's disease continuum cohort, the area under the curve (AUC), sensitivity, specificity, and accuracy for the p‐tau217/Aβ42 ratio reached 0.961, 93%, 92%, and 93%, respectively. Validation in an intention‐to‐treat cohort demonstrated similar AUC (0.959), with increased sensitivity (99%), decreased specificity (87%), and increased accuracy (95%). Dual cut‐offs generating balanced 95% sensitivity/specificity result in 93% accuracy.DISCUSSIONCombinations of plasma p‐tau217 and Aβ42 demonstrate recommended performance, confirming the presence of Aβ positivity prior to selection for disease‐modifying therapies.HighlightsThe phosphorylated tau (p‐tau)217/amyloid beta (Aβ)42 ratio had high performance to detect Aβ positron emission tomography (PET) status, with > 90% sensitivity, specificity, and accuracy.p‐tau217/Aβ42 ratio dual cut‐offs set at 95% sensitivity and specificity found 10% to 15% of participants in the intermediate zone.Cut‐offs derived for the intention‐to‐treat cohort meet confirmatory assay criteria for a disease‐modifying therapy and can be used in clinical settings.

BackgroundPeople living with Alzheimer's disease and other types of dementia are vulnerable to medicine-related problems. More research is needed to support achieving quality use of medicines in people living with dementia.ObjectiveTo determine the top 10 unanswered quality use of medicines questions for people living with dementia, as prioritized by Australians living with dementia, their carers, and healthcare professionals.MethodsThe James Lind Alliance Priority Setting Partnership method was used. This manuscript reports the second half of the priority setting process. Using a quantitative survey, consumers (people living with dementia, their carers and family and friends) and healthcare professionals selected up to ten research questions about quality use of medicines that they felt were most important. The research questions were informed by a previous national qualitative survey and evidence checking process to identify those that were unanswered. An online workshop was then conducted with consumers and healthcare professionals to prioritize the unanswered questions, resulting in a top 10 list.Results171 consumers and 67 healthcare professionals completed the survey and the workshop included 17 participants. The top 10 priorities related to shared decision making, education of healthcare professionals, communication between healthcare professionals, reducing the use of unnecessary and harmful medicines, managing medicines safely at home, medicine reviews, residential aged care facilities and managing pain, behavioral changes, depression and anxiety.ConclusionsTargeting research efforts towards these identified consumer and healthcare professional priorities will ensure research funds are being directed to the most urgent areas of need in practice.

Abstract BackgroundIn cognitively unimpaired (CU) individuals, the PACC is widely used as a cognitive outcome measure and endpoint in observational studies and clinical trials. However, it has drawn criticism for being heavily weighted towards memory. Increasing evidence indicates a decline spanning multiple cognitive domains in CU individuals. Therefore, using principal component analysis (PCA), we derived data‐driven domain‐specific cognitive composites. And subsequently, compared them against their summed z‐score counterparts in predicting progression to mild cognitive impairment (MCI).MethodBaseline cognitive, demographic, and genotype data of 2,853 CU older adults (aged 41.6 to 98.3) was obtained from the Alzheimer’s Dementia Onset and Progression in International Cohorts (ADOPIC) Consortium. Using varimax‐rotated PCA, tests significantly loading (≥ 0.5) onto each principal component were extracted to derive domain‐specific cognitive composites. The resulting domain scores were normalised to a mean of 0 and SD of 1, with a higher score indicating better cognition. Cox regression was used to assess the association between progression to MCI and baseline demographics, cognition, and APOE ε4 carriage. Akaike information criteria (AIC) was used to compare the fitness of PCA‐derived composites against the zPACC and z‐score domain‐specific composites.ResultBaseline cohort characteristics are described in Table 1. PCA explained 68% of the variance and resulted in four independent cognitive composites (Figure 1): memory; executive function; attention and processing speed; and global cognition. At 15 years from baseline, 309 participants progressed to MCI, while 2,544 remained CU. Cox regression showed that the four cognitive composites, age and APOE genotype significantly predicted progression to MCI (Concordance = 77%, p < 0.001, AIC = 4105, Table 1). Additionally, the PCA‐derived composites performed comparably, if not better than the summed z‐score counterparts, the PACC (Concordance = 74%, p < 0.001, AIC = 4163) and domain‐specific composites (Concordance = 75%, p < 0.001, AIC = 4142). Baseline older age, APOE ε4 carriage in a dose‐dependent manner (Figure 2) and poorer cognition for each PCA‐composite were independently associated with progression to MCI.ConclusionTogether with APOE ε4 carriage, our PCA‐derived domain‐specific composites performed better than their summed z‐score counterparts at predicting progression to MCI 15 years before symptom onset.

Abstract BackgroundEvidence suggests that diet may play a modifiable role in reducing Alzheimer’s disease (AD) risk. Higher adherence to the Mediterranean diet (MeDi) is linked to a lower incidence of mild cognitive impairment (MCI) and AD. Increasing evidence indicates the potential utility of a cytoskeletal protein found in astrocytes, plasma Glial Fibrillary Acidic Protein (GFAP), as a marker specific for AD pathogenesis. However, the relationship between plasma GFAP level and the MeDi has not been fully determined. This cross‐sectional study examined whether MeDi diet as a whole or the individual components, were associated with plasma GFAP levels in an Australian older adult cohort drawn from the larger Australian Imaging, Biomarkers and Lifestyle (AIBL) study of ageing.MethodsCognitively unimpaired participants (n = 116) and individuals with MCI (n = 47) (mean age 75.37 ± 6.31; 44% male) completed a self‐reported food frequency questionnaire and had plasma GFAP levels measured using SIMOA platform. A score for the MeDi was generated for each individual. Linear regression models evaluated the association between plasma GFAP and the MeDi score, as well as individual MeDi components, including sex and age as covariates.ResultsMeDi score was not associated with plasma GFAP level. However, for individual MeDi components, dairy intake was positively associated with GFAP level (β = 0.107±0.039, p = 0.007).ConclusionsThis study is one of the first to report an association of plasma GFAP level with dietary components in an older adult cohort. The results suggest that dairy intake influences astrocyte reactivity. Further studies will include evaluation of plasma GFAP levels with additional dietary patterns, and individual dietary components to fully investigate the modifiable effect of diet on AD process.

Abstract BackgroundLifestyle modifications incorporating a healthy diet, physical activity, brain training and health monitoring have proven effective in preventing dementia and related cognitive decline (REF). The Australian‐Multidomain Lifestyle Intervention to reduce dementia risk (AU‐ARROW) is an ongoing 2‐yearintervention, which is the Australian contribution to the World‐Wide FINGERS network. Here we report on preliminary findings of baseline dietary energy and nutrient intakes of AU‐ARROW participants.MethodsData from 99 cognitively‐unimpaired adults enrolled in AU‐ARROW were included (60% female; mean age 67.8±5.3 years). Participants self‐administered the validated Cancer Council of Victoria Food Frequency Questionnaire at baseline, which was used to analyse dietary energy and nutrient intake. Nutrient intakes were compared against the Australian National Health and Medical Research Council Recommended Dietary Intakes (RDIs).ResultsParticipants’ average energy and protein intakes were 8980±1980 kJ/day and 96.8±22.6 g/day for males, and 8250±2660 kJ/day and 88.1±25.3 g/day for females. Total fat intake (males 101±25.8 g/day, females 98.9±37.0 g/day) comprised approximately 31% saturated fat, 45% monounsaturated fat and 18% polyunsaturated fat. RDIs were met by participants for most vitamins and minerals, with exceptions for sodium, zinc, calcium, vitamin A, thiamine, riboflavin, vitamin D and iodine. Males exhibited higher sodium intake (2410±588 mg/day) than the Recommended Upper Level of Intake (2300 mg/day), and lower zinc (10.9±2.7 mg/day) and vitamin A (797±310 mg/day) intake than the RDI (Zinc 14 mg/day, vitamin A 900 mg/day). Females exhibited lower thiamine (0.8±0.6 mg/day) and riboflavin (1.0±0.7 mg/day) intake than the RDI (1.1 mg/day for both). Both genders exhibited lower calcium intake (males 856±264 mg/day, females 860±345 mg/day), and iodine (males 123±40.1 µg/day, females 125±54.9 µg/day) than the RDI (calcium: males 1000 mg/day, females 1300 mg/day, iodine: 150 µg/day for both).ConclusionHabitual macro‐nutrient intakes of AU‐ARROW participants largely meet the RDI for Australians, except for higher saturated fat and lower calcium and iodine intakes. The Australian Health Survey:2011‐2012 has also reported similar concerns on Australians’ usual nutrient intakes. Attention to a healthy diet is crucial for optimal saturated fat, vitamin, and mineral levels. These baseline data identify deficiencies in the Australian diet which hopefully will be corrected following dietary‐intervention of the AU‐ARROW participants.