Sir James McCusker Alzheimers Disease Research Unit Hollywood Private Hospital

Perth, Australia

Sir James McCusker Alzheimers Disease Research Unit Hollywood Private Hospital

Perth, Australia
SEARCH FILTERS
Time filter
Source Type

Bird S.M.,University of Western Australia | Bird S.M.,Sir James McCusker Alzheimers Disease Research Unit Hollywood Private Hospital | Sohrabi H.R.,University of Western Australia | Sohrabi H.R.,Edith Cowan University | And 24 more authors.
Neuroscience and Biobehavioral Reviews | Year: 2016

Traumatic brain injury (TBI) increases the risk of neurodegenerative disorders many years post-injury. However, molecular mechanisms underlying the relationship between TBI and neurodegenerative diseases, such as Alzheimer's disease (AD), remain to be elucidated. Nevertheless, previous studies have demonstrated a link between TBI and increased amyloid-β (Aβ), a protein involved in AD pathogenesis. Here, we review animal studies that measured Aβ levels following TBI. In addition, from a pool of initially identified 1209 published papers, we examined data from 19 eligible animal model studies using a meta-analytic approach. We found an acute increase in cerebral Aβ levels ranging from 24 h to one month following TBI (overall log OR = 2.97 ± 0.40, p < 0.001). These findings may contribute to further understanding the relationship between TBI and future dementia risk. The methodological inconsistencies of the studies discussed in this review suggest the need for improved and more standardised data collection and study design, in order to properly elucidate the role of TBI in the expression and accumulation of Aβ. © 2016 Elsevier Ltd.


Pike K.E.,Center for PET | Pike K.E.,Mental Health Research Institute | Pike K.E.,University of Melbourne | Pike K.E.,La Trobe University | And 20 more authors.
Neuropsychologia | Year: 2011

The 'preclinical' phase of Alzheimer's disease is a future target for treatment, but additional research is essential to understand the relationship between β-amyloid burden and cognition during this time. We investigated this relationship using a large sample of apparently healthy older adults (N=177), which also enabled examination of whether the relationship differed according to age, gender, years of education, apolipoprotein E status, and the presence of subjective memory complaints. In addition to episodic memory, a range of cognitive measures (global cognition, semantic memory, visuospatial performance, and executive function) were examined. Participants were aged over 60 years with no objective cognitive impairment and came from the imaging arm of the Australian Imaging, Biomarkers, and Lifestyle (AIBL) study of ageing. 11C-PiB PET was used to measure β-amyloid burden and a PiB 'cut-off' level of 1.5 was used to separate participants with low PiB retention from those with high PiB retention. Thirty-three percent of participants had a PiB positive scan. PiB positive participants were 5 years older, twice as likely to carry an apolipoprotein E e{open}4 allele, and their composite episodic memory was 0.26 SD worse than PiB negative volunteers. Linear regressions with β-amyloid burden as a dichotomous predictor, revealed an interaction between β-amyloid burden and gender, as well as age and education effects, in predicting episodic memory and visuospatial performance. In females, but not in males, increased β-amyloid was related to worse episodic memory and visuospatial performance. Furthermore, an interaction between β-amyloid burden and APOE status was found in predicting visuospatial performance, whereby there was a trend for increased β-amyloid to relate to worse visuospatial performance for those without an APOE e{open}4 allele. There were no other main or interaction effects of β-amyloid on any of the other composite cognitive measures. These cross-sectional findings suggest that β-amyloid burden does not have a large effect on cognition in this subset of apparently healthy older people. The finding of gender differences deserves further research to answer definitively the important question of gender susceptibility to adverse cognitive effects from β-amyloid. © 2011 Elsevier Ltd.


Verdile G.,Edith Cowan University | Verdile G.,Sir James McCusker Alzheimers Disease Research Unit Hollywood Private Hospital | Laws S.M.,Edith Cowan University | Laws S.M.,Sir James McCusker Alzheimers Disease Research Unit Hollywood Private Hospital | And 30 more authors.
Molecular Psychiatry | Year: 2014

Testosterone and gonadotropins have been associated with cognitive decline in men and the modulation of β amyloid (Aβ) metabolism. The relatively few studies that have investigated whether changes in one or a combination of these hormones influence Aβ levels have focused primarily on plasma Aβ 1-40 and not on the more pathogenic Aβ 1-42. Currently, no study has investigated whether these hormones are associated with an increase in brain amyloid deposition, ante mortem. Through the highly characterised Australian imaging, biomarkers and lifestyle study, we have determined the impact of these hormones on plasma Aβ levels and brain amyloid burden (Pittsburgh compound B (PiB) retention). Spearman's rank correlation and linear regression analysis was carried out across the cohort and within subclassifications. Luteinizing hormone (LH) was the only variable shown, in the total cohort, to have a significant impact on plasma Aβ 1-40 and Aβ 1-42 levels (beta=0.163, P<0.001; beta=0.446, P<0.001). This held in subjective memory complainers (SMC) (Aβ 1-40; beta=0.208, P=0.017; Aβ 1-42; beta=0.215, P=0.017) but was absent in mild cognitive impairment (MCI) and Alzheimer's disease (AD) groups. In SMC, increased frequency of the APOE-ε4 allele (beta=0.536, P<0.001) and increasing serum LH levels (beta=0.421, P=0.004) had a significant impact on PiB retention. Whereas in MCI, PiB retention was associated with increased APOE-ε4 allele copy number (beta=0.674, P<0.001) and decreasing calculated free testosterone (beta=-0.303, P=0.043). These findings suggest a potential progressive involvement of LH and testosterone in the early preclinical stages of AD. Furthermore, these hormones should be considered while attempting to predict AD at these earliest stages of the disease. © 2014 Macmillan Publishers Limited.


PubMed | Sir James McCusker Alzheimers Disease Research Unit Hollywood Private Hospital, Austin Health, National Ageing Research Institute, University of Melbourne and CSIRO
Type: Journal Article | Journal: Journal of Alzheimer's disease : JAD | Year: 2014

We evaluated the utility of longitudinal measures of plasma amyloid- (A) as a means to identify pre-symptomatic cognitive decline in Alzheimers disease (AD) when coupled to neuroimaging and neuropsychological parameters.Participants from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study were grouped based upon cognitive change and changes in measurable levels of neocortical amyloid over 36 months. Participants were classified as those who transitioned for cognitive decline and change in neocortical amyloid, those healthy controls that did not transition, and stable AD participants over 36 months.Comparisons of plasma A levels between the transition and non-transitional groups showed A1-42 and the A1-42/A1-40 ratio were significantly decreased at baseline (p = 0.008 and p = 0.002, respectively) and at 18 months (p = 0.003 and p = 0.004, respectively). Both measures of neocortical amyloid and two previously published composite scores validated the creation of the novel transitional grouping (p < 0.0001). In addition An-42 performed well as a longitudinal prognostic indicator of transition toward cognitive decline, with a significant decrease in the transition group at the 18 month time point (p = 0.01).We demonstrated that baseline plasma A1-42 and the A1-42/A1-40 ratio were putative biomarkers indicative of cognitive decline and validated this result using 18 month data. We created a novel transitional grouping and validated this measure using published measures of neocortical amyloid and composite memory scores. These findings suggest that longitudinal plasma A could contribute to a pre-symptomatic biomarker panel for AD.


PubMed | St. George's University, Macquarie University, Sir James McCusker Alzheimers Disease Research Unit Hollywood Private Hospital, CogState Ltd and 5 more.
Type: Journal Article | Journal: International psychogeriatrics | Year: 2014

The Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing is a prospective study of 1,112 individuals (211 with Alzheimers disease (AD), 133 with mild cognitive impairment (MCI), and 768 healthy controls (HCs)). Here we report diagnostic and cognitive findings at the first (18-month) follow-up of the cohort. The first aim was to compute rates of transition from HC to MCI, and MCI to AD. The second aim was to characterize the cognitive profiles of individuals who transitioned to a more severe disease stage compared with those who did not.Eighteen months after baseline, participants underwent comprehensive cognitive testing and diagnostic review, provided an 80 ml blood sample, and completed health and lifestyle questionnaires. A subgroup also underwent amyloid PET and MRI neuroimaging.The diagnostic status of 89.9% of the cohorts was determined (972 were reassessed, 28 had died, and 112 did not return for reassessment). The 18-month cohort comprised 692 HCs, 82 MCI cases, 197 AD patients, and one Parkinsons disease dementia case. The transition rate from HC to MCI was 2.5%, and cognitive decline in HCs who transitioned to MCI was greatest in memory and naming domains compared to HCs who remained stable. The transition rate from MCI to AD was 30.5%.There was a high retention rate after 18 months. Rates of transition from healthy aging to MCI, and MCI to AD, were consistent with established estimates. Follow-up of this cohort over longer periods will elucidate robust predictors of future cognitive decline.


O'Bryant S.E.,University of North Texas Health Science Center | Xiao G.,University of Texas Southwestern Medical Center | Edwards M.,University of North Texas Health Science Center | Edwards M.,University of North Texas | And 7 more authors.
Journal of Alzheimer's Disease | Year: 2013

Background: Mexican Americans are the fastest aging segment of the U.S. population, yet little scientific literature exists regarding the Alzheimer's disease (AD) among this segment of the population. The extant literature suggests that biomarkers of AD will vary according to race/ethnicity though no prior work has explicitly studied this possibility. The aim of this study was to create a serum-based biomarker profile of AD among Mexican American. Methods: Data were analyzed from 363 Mexican American participants (49 AD and 314 normal controls) enrolled in the Texas Alzheimer's Research & Care Consortium (TARCC). Non-fasting serum samples were analyzed using a luminex-based multi-plex platform. A biomarker profile was generated using random forest analyses. Results: The biomarker profile of AD among Mexican Americans was different from prior work from non-Hispanic populations with regards to the variable importance plots. In fact, many of the top markers were related to metabolic factors (e.g., FABP, GLP-1, CD40, pancreatic polypeptide, insulin-like-growth factor, and insulin). The biomarker profile was a significant classifier of AD status yielding an area under the receiver operating characteristic curve, sensitivity, and specificity of 0.77, 0.92, and 0.64, respectively. Combining biomarkers with clinical variables yielded a better balance of sensitivity and specificity. Conclusion: The biomarker profile for AD among Mexican American cases is significantly different from that previously identified among non-Hispanic cases from many large-scale studies. This is the first study to explicitly examine and provide support for blood-based biomarkers of AD among Mexican Americans. Areas for future research are highlighted. © 2013 - IOS Press and the authors. All rights reserved.


Moore E.M.,University of Melbourne | Moore E.M.,Barwon Health | Mander A.G.,Barwon Health | Ames D.,University of Melbourne | And 21 more authors.
Diabetes Care | Year: 2013

OBJECTIVE To investigate the associations of metformin, serum vitamin B12, calciumsupplements, and cognitive impairment in patients with diabetes. RESEARCH DESIGN AND METHODSdParticipants were recruited from the Primary Research in Memory (PRIME) clinics study, the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, and the Barwon region of southeastern Australia. Patients with Alzheimer disease (AD) (n = 480) or mild cognitive impairment (n = 187) and those who were cognitively intact (n = 687) were included; patients with stroke or with neurodegenerative diseases other than AD were excluded. Subgroup analyses were performed for participants who had either type 2 diabetes (n = 104) or impaired glucose tolerance (n = 22). RESULTSdParticipants with diabetes (n = 126) had worse cognitive performance than participants who did not have diabetes (n = 1,228; adjusted odds ratio 1.51 [95% CI 1.03-2.21]). Among participants with diabetes, worse cognitive performance was associated with metformin use (2.23 [1.05-4.75]). After adjusting for age, sex, level of education, history of depression, serum vitamin B12, and metformin use, participants with diabetes who were taking calcium supplements had better cognitive performance (0.41 [0.19-0.92]). CONCLUSIONSdMetformin use was associated with impaired cognitive performance. Vitamin B12 and calciumsupplementsmay alleviate metformin-induced vitamin B12 deficiency and were associated with better cognitive outcomes. Prospective trials are warranted to assess the beneficial effects of vitamin B12 and calcium use on cognition in older people with diabetes who are taking metformin. © 2013 by the American Diabetes Association.


Ellis K.A.,University of Melbourne | Ellis K.A.,Florey Institute of Neuroscience and Mental Health | Ellis K.A.,National Ageing Research Institute NARI | Rainey-Smith S.R.,Sir James McCusker Alzheimers Disease Research Unit Hollywood Private Hospital | And 5 more authors.
International Review of Psychiatry | Year: 2013

The Australian Imaging Biomarkers and Lifestyle (AIBL) study is a longitudinal study of 1,112 volunteers from healthy, mild cognitive impairment (MCI) and Alzheimer's disease (AD) populations who are assessed at 18-month intervals in order to enable prospective research into ageing and AD. Using a multidisciplinary battery, AIBL assessments comprise the extensive study of clinical factors and cognitive function, collection of blood and cerebrospinal fluid (CSF) samples for biomarker discovery, structural and β-amyloid (Aβ) neuroimaging, and obtaining information on diet and physical activity patterns of the cohort. Now in its seventh year, AIBL is part of a substantial international effort to prospectively study the relationships between clinical characteristics and putative AD biomarkers in groups who carry different risk factors for AD. The identification of biomarkers would provide a window of opportunity to assess AD risk in individuals prior to the onset of advanced clinical symptoms, in addition to facilitating testing of therapeutic and lifestyle interventions likely to emerge within the next decade that prevent or delay symptom emergence in those at high risk for developing AD. In this paper, we present key findings from the AIBL study and discuss how they contribute to our understanding of AD pathogenesis and diagnosis. © 2013 Institute of Psychiatry.


Gupta V.B.,Edith Cowan University | Sundaram R.,Center for Ageing and Alzheimers | Martins R.N.,Edith Cowan University | Martins R.N.,Sir James McCusker Alzheimers Disease Research Unit Hollywood Private Hospital | Martins R.N.,Hollywood Medical Center
Alzheimer's Research and Therapy | Year: 2013

Advances in the field of blood biomarker discovery will help in identifying Alzheimer's disease in its preclinical stage, allowing treatment to be initiated before irreversible damage occurs. This review discusses some recent past and current approaches being taken by researchers in the field. Individual blood biomarkers have been unsuccessful in defining the disease pathology, progression and thus diagnosis. This directs to the need for discovering a multiplex panel of blood biomarkers as a promising approach with high sensitivity and specificity for early diagnosis. However, it is a great challenge to standardize a worldwide blood biomarker panel due to the innate differences in the population tested, nature of the samples and methods utilised in different studies across the globe. We highlight several issues that result in the lack of reproducibility in this field of research currently faced by researchers. Several important measures are summarized towards the end of the review that can be taken to minimize the variability among various centres. © 2013 BioMed Central Ltd.


PubMed | Sir James McCusker Alzheimers Disease Research Unit Hollywood Private Hospital, Hollywood Medical Center, University of Western Australia, London Health Sciences Center and Edith Cowan University
Type: | Journal: Neuroscience and biobehavioral reviews | Year: 2016

Traumatic brain injury (TBI) increases the risk of neurodegenerative disorders many years post-injury. However, molecular mechanisms underlying the relationship between TBI and neurodegenerative diseases, such as Alzheimers disease (AD), remain to be elucidated. Nevertheless, previous studies have demonstrated a link between TBI and increased amyloid- (A), a protein involved in AD pathogenesis. Here, we review animal studies that measured A levels following TBI. In addition, from a pool of initially identified 1209 published papers, we examined data from 19 eligible animal model studies using a meta-analytic approach. We found an acute increase in cerebral A levels ranging from 24h to one month following TBI (overall log OR=2.97 0.40, p<0.001). These findings may contribute to further understanding the relationship between TBI and future dementia risk. The methodological inconsistencies of the studies discussed in this review suggest the need for improved and more standardised data collection and study design, in order to properly elucidate the role of TBI in the expression and accumulation of A.

Loading Sir James McCusker Alzheimers Disease Research Unit Hollywood Private Hospital collaborators
Loading Sir James McCusker Alzheimers Disease Research Unit Hollywood Private Hospital collaborators