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  • 1
    Online Resource
    Online Resource
    Cambridge University Press (CUP) ; 2020
    In:  International Psychogeriatrics Vol. 32, No. S1 ( 2020-10), p. 73-73
    In: International Psychogeriatrics, Cambridge University Press (CUP), Vol. 32, No. S1 ( 2020-10), p. 73-73
    Abstract: Neurofibrillary tangles (NFT) formed by tau proteins, a pathological hallmark of Alzheimer’s disease, are a common co-pathology in people with Lewy body dementias, which include dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD). Aims: To investigate the prevalence of tau in Lewy body dementia, and its association with clinical outcomes. Methods: A systematic search was conducted on Medline, Embase and PubMed using the search term: (“dementia with Lewy bodies” OR “diffuse Lewy body disease”) AND (“tau protein” OR “tauopathy” OR “neurofibrillary tangle”). A total of 42 articles met the inclusion criteria for data extraction. Random-effect meta-analyses were performed to obtain pooled estimates for prevalence, and risk ratios (RR) or standardised mean difference (SMD) for clinical outcomes measures. Results: Braak NFT stage ≥III was observed in 67% (n=1399, 95%CI 59%-76%) of DLB and 52% (n=429, 95%CI 26%-78%) of PDD at autopsy. Abnormal CSF phosphorylated-tau levels were present in 27% (n=705, 95%CI 23%-30%) of DLB and 15% (n=172, 95%CI 5%-24%) of PDD cases. Higher tau burden in DLB was associated with reduced likelihood of manifesting visual hallucinations (RR 0.56; 95%CI 0.40-0.77) and motor parkinsonism (RR 0.62; 95%CI 0.40-0.98), lower diagnostic accuracy of DLB during life (RR 0.49; 95%CI 0.38-0.64) and worse cognition prior to death (SMD 0.60; 95%CI 0.44-0.76). Conclusions: Tau is more common in DLB than PDD and may negatively impact clinical diagnostic accuracy in people with DLB. Prospective longitudinal studies are needed to understand the roles of co-morbid neuropathologies in Lewy body dementias.
    Type of Medium: Online Resource
    ISSN: 1041-6102 , 1741-203X
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2147136-8
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  • 2
    In: Nutrients, MDPI AG, Vol. 13, No. 10 ( 2021-10-07), p. 3516-
    Abstract: Preventive zinc supplementation provided as a stand-alone dispersible tablet, or via home fortification as multiple micronutrient powders (MNPs), has been considered a potential strategy to prevent zinc deficiency and improve health (including immune) outcomes among children in low- and middle-income countries. However, the impact of zinc supplementation on immune profiles has not been well characterized. We sought to define the effect of zinc supplementation on peripheral blood gene expression and cytokine levels among young children in Dhaka, Bangladesh. In a sub-study of a large randomized, controlled, community-based efficacy trial where children 9–11 months of age received one of the following interventions on a daily basis for 24 weeks: (1) MNPs containing 10 mg of zinc; (2) dispersible tablet containing 10 mg zinc; or (3) placebo powder, we used RNA sequencing to profile the peripheral blood gene expression, as well as highly sensitive multiplex assays to detect cytokine profiles. We profiled samples from 100 children enrolled in the parent trial (zinc MNPs 28, zinc tablets 39, placebo 33). We did not detect an effect from either zinc intervention on differential peripheral blood gene expression at the end of the intervention, or an effect from the intervention on changes in gene expression from baseline. We also did not detect an effect from either intervention on cytokine concentrations. Exploratory analysis did not identify an association between undernutrition (defined as stunting, underweight or wasting) and peripheral blood gene expression. Zinc interventions in children did not produce a gene expression or cytokine signature in the peripheral blood. However, this study demonstrates a proof of principle that sensitive multi-omic techniques can be applied to samples collected in field studies.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2518386-2
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  • 3
    In: Internal Medicine Journal, Wiley, Vol. 53, No. 6 ( 2023-06), p. 907-916
    Abstract: Cerebral amyloid angiopathy (CAA) is a disease with several clinical manifestations. It is characterised by amyloid‐beta deposition in cerebral blood vessels, making them prone to bleeding. The incidence of CAA increases with age and may be associated or co‐exist with intraparenchymal neurodegenerative proteinopathies, which makes it an increasingly relevant condition for adult physicians in all areas of medical practice. The vast majority of cases of CAA are sporadic with a small minority of familial cases. CAA is asymptomatic in many older adults but increases the risk of fatal intracerebral or subarachnoid haemorrhage. We review the existing literature on CAA and summarise the key findings. We specifically explore clinical challenges relevant to CAA, particularly in diagnosis, management of intracranial haemorrhage and management of concurrent medical conditions.
    Type of Medium: Online Resource
    ISSN: 1444-0903 , 1445-5994
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2044081-9
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  • 4
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. 8 ( 2022-08)
    Abstract: Recent reports raise the possibility of cerebral amyloid angiopathy (CAA) leading to intracerebral hemorrhage in young adults following childhood neurosurgery, suggesting transmission of amyloid-β (Aβ) through neurosurgical procedures including dura mater grafting. Parenchymal Aβ deposition, and to a lesser extent tau aggregation, similar to that seen in Alzheimer disease, have also been described. Methods: We conducted a database review of 634 consecutive intracerebral hemorrhage patients aged 〈 65 years at a tertiary stroke center over 20 years to identify such patients. Results: We identified 3 patients aged in their thirties who presented with spontaneous lobar intracerebral hemorrhage, with imaging or neuropathology consistent with CAA, and a history of childhood neurosurgery. Two of these patients had undergone a dural repair using cadaveric dura mater (Lyodura). In addition to CAA, both patients had neuropathologically confirmed parenchymal Aβ and tau deposits, characteristic of Alzheimer disease. Conclusions: Our findings support the concept of neurosurgical Aβ transmission but suggest that such cases are rare in standard clinical practice.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1467823-8
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  • 5
    Online Resource
    Online Resource
    Wiley ; 2019
    In:  Alzheimer's & Dementia Vol. 15, No. 7S_Part_27 ( 2019-07)
    In: Alzheimer's & Dementia, Wiley, Vol. 15, No. 7S_Part_27 ( 2019-07)
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2201940-6
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  • 6
    In: Alzheimer's & Dementia, Wiley, Vol. 17, No. S5 ( 2021-12)
    Abstract: Accurate, timely diagnosis of neurodegenerative disorders, in particular distinguishing primary psychiatric from neurological disorders and in younger people, can be challenging. There is a need for biomarkers to reduce the diagnostic odyssey and improve outcomes. Neurofilament light (NfL) has shown promise as a diagnostic biomarker in a wide range of disorders. Our Markers in Neuropsychiatric Disorders (MiND) Study builds on our pilot (Eratne et al, ANZJP, 2020), to explore the diagnostic and broader utility of plasma and cerebrospinal fluid (CSF) NfL and other novel markers such as phosphorylated tau 181 (p‐tau181), in a broad range of psychiatric and neurodegenerative/neurological disorders, with a view of translation into routine clinical practice. Methods We assessed plasma and/or CSF NfL and p‐tau181 concentrations in broad cohorts, including: patients assessed for neurocognitive/psychiatric symptoms at Neuropsychiatry and Melbourne Young‐Onset Dementia services and other services, in a wide range of disorders including Alzheimer disease, frontotemporal dementia, schizophrenia, bipolar disorder, depression, Niemann‐Pick Type C, epilepsy, functional neurological disorders. The most recent primary consensus diagnosis informed by established diagnostic criteria was categorised: primary psychiatric disorder (PPD), neurodegenerative/neurological disorder (ND), or healthy controls (HC). Results Findings from over 500 patients/participants will be presented, which indicate that CSF and plasma NfL levels are significantly elevated in a broad range of ND compared to a broad range of PPD, and HC, and bvFTD progressors from phenocopy syndromes, differentiating with areas under the curve of 〉 0.90, sensitivity and specificity 〉 90%. Plasma P‐tau181 levels distinguished Alzheimer disease (mainly younger sporadic), compared to other neurodegenerative disorders, with AUC 0.90, 90% sensitivity and specificity. As recruitment, sample analysis, data collection is ongoing, the most up to date results will be presented. Conclusions NfL shows great promise as a diagnostic test to assist with the common, challenging diagnostic dilemma of distinguishing neurodegenerative from non‐neurodegenerative and primary psychiatric disorders. Plasma p‐tau181 shows strong diagnostic utility in younger‐onset Alzheimer disease. A significantly elevated NfL in someone with a psychiatric diagnosis should prompt consideration of neurodegenerative differentials. Plasma NfL could dramatically alter clinical care of patients with neuropsychiatric and neurological symptoms, improving outcomes for patients, their families, the healthcare system, and clinical trials.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2201940-6
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  • 7
    Online Resource
    Online Resource
    Elsevier BV ; 2022
    In:  Parkinsonism & Related Disorders Vol. 104 ( 2022-11), p. 68-71
    In: Parkinsonism & Related Disorders, Elsevier BV, Vol. 104 ( 2022-11), p. 68-71
    Type of Medium: Online Resource
    ISSN: 1353-8020
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 2027635-7
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  • 8
    Online Resource
    Online Resource
    Wiley ; 2022
    In:  Internal Medicine Journal Vol. 52, No. 12 ( 2022-12), p. 2181-2185
    In: Internal Medicine Journal, Wiley, Vol. 52, No. 12 ( 2022-12), p. 2181-2185
    Abstract: The burden of dementia will increase as the Australian population ages and grows in coming decades. Early and accurate diagnosis remains challenging, and disproportionately so for particular groups, including rural communities. Recent advances in technology, however, now allow reliable measurement of blood biomarkers that could improve diagnosis in a range of settings. We discuss the most promising biomarker candidates for translation into clinical practice and research in the near future.
    Type of Medium: Online Resource
    ISSN: 1444-0903 , 1445-5994
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2044081-9
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  • 9
    Online Resource
    Online Resource
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 15 ( 2023-07-28), p. 12116-
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 15 ( 2023-07-28), p. 12116-
    Abstract: Inflammatory mechanisms are increasingly recognized as important contributors to the pathogenesis of neurodegenerative diseases, including Lewy body dementia (LBD). Our objectives were to, firstly, review inflammation investigation methods in LBD (dementia with Lewy bodies and Parkinson’s disease dementia) and, secondly, identify alterations in inflammatory signals in LBD compared to people without neurodegenerative disease and other neurodegenerative diseases. A systematic scoping review was performed by searching major electronic databases (MEDLINE, Embase, Web of Science, and PSYCHInfo) to identify relevant human studies. Of the 2509 results screened, 80 studies were included. Thirty-six studies analyzed postmortem brain tissue, and 44 investigated living subjects with cerebrospinal fluid, blood, and/or brain imaging assessments. Largely cross-sectional data were available, although two longitudinal clinical studies investigated prodromal Lewy body disease. Investigations were focused on inflammatory immune cell activity (microglia, astrocytes, and lymphocytes) and inflammatory molecules (cytokines, etc.). Results of the included studies identified innate and adaptive immune system contributions to inflammation associated with Lewy body pathology and clinical disease features. Different signals in early and late-stage disease, with possible late immune senescence and dystrophic glial cell populations, were identified. The strength of these associations is limited by the varying methodologies, small study sizes, and cross-sectional nature of the data. Longitudinal studies investigating associations with clinical and other biomarker outcomes are needed to improve understanding of inflammatory activity over the course of LBD. This could identify markers of disease activity and support therapeutic development.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 10
    Online Resource
    Online Resource
    SAGE Publications ; 2023
    In:  Australian & New Zealand Journal of Psychiatry
    In: Australian & New Zealand Journal of Psychiatry, SAGE Publications
    Abstract: Neurofibrillary tangles are present in a proportion of people with dementia with Lewy bodies and may be associated with worse cognition. Recent advances in biomarkers for Alzheimer’s disease include second-generation tau positron emission tomography as well as the detection of phosphorylated tau at threonine 181 (p-tau181) in plasma. This study aimed to investigate tau in people with dementia with Lewy bodies using a second-generation tau positron emission tomography tracer as well as plasma p-tau181. Methods: Twenty-seven participants (mean age 74.7 ± 5.5) with clinically diagnosed probable dementia with Lewy bodies underwent comprehensive clinical assessment and positron emission tomography imaging ( 18 F-MK6240 and 18 F-NAV4694). Plasma p-tau181 levels were measured using Simoa technology. Results: Five dementia with Lewy bodies participants (18.5%) had an abnormal tau positron emission tomography (increased tau uptake in the temporal meta-region-of-interest). Higher plasma p-tau181 concentrations correlated with higher tau deposition in the temporal region (ρ = 0.46, 95% confidence interval = [0.10, 0.72]) and classified abnormal tau positron emission tomography in dementia with Lewy bodies with an area under the curve of 0.95 (95% confidence interval = [0.86, 0.99] ). Plasma p-tau181 also correlated positively with cortical amyloid-beta binding (ρ = 0.68, 95% confidence interval = [0.40, 0.84]) and classified abnormal amyloid-beta positron emission tomography in dementia with Lewy bodies with an area under the curve of 0.91 (95% confidence interval = [0.79, 0.99] ). There was no association found between tau deposition and any of the clinical variables. Conclusions: Tau is a common co-pathology in dementia with Lewy bodies. Plasma p-tau181 correlated with abnormal tau and amyloid-beta positron emission tomography and may potentially be used as a marker to identify co-morbid Alzheimer’s disease-related pathology in dementia with Lewy bodies. The clinical implications of tau in dementia with Lewy bodies need to be further evaluated in larger longitudinal studies.
    Type of Medium: Online Resource
    ISSN: 0004-8674 , 1440-1614
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2023
    detail.hit.zdb_id: 2003849-5
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