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Publications (9)42.77 Total impact

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    ABSTRACT: Dementia is a global epidemic with Alzheimer's disease (AD) being the leading cause. Early identification of patients at risk of developing AD is now becoming an international priority. Neocortical Aβ (extracellular β-amyloid) burden (NAB), as assessed by positron emission tomography (PET), represents one such marker for early identification. These scans are expensive and are not widely available, thus, there is a need for cheaper and more widely accessible alternatives. Addressing this need, a blood biomarker-based signature having efficacy for the prediction of NAB and which can be easily adapted for population screening is described. Blood data (176 analytes measured in plasma) and Pittsburgh Compound B (PiB)-PET measurements from 273 participants from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study were utilised. Univariate analysis was conducted to assess the difference of plasma measures between high and low NAB groups, and cross-validated machine-learning models were generated for predicting NAB. These models were applied to 817 non-imaged AIBL subjects and 82 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) for validation. Five analytes showed significant difference between subjects with high compared to low NAB. A machine-learning model (based on nine markers) achieved sensitivity and specificity of 80 and 82%, respectively, for predicting NAB. Validation using the ADNI cohort yielded similar results (sensitivity 79% and specificity 76%). These results show that a panel of blood-based biomarkers is able to accurately predict NAB, supporting the hypothesis for a relationship between a blood-based signature and Aβ accumulation, therefore, providing a platform for developing a population-based screen.Molecular Psychiatry advance online publication, 30 April 2013; doi:10.1038/mp.2013.40.
    Molecular Psychiatry 04/2013; DOI:10.1038/mp.2013.40 · 15.15 Impact Factor
  • Neurobiology of Aging 05/2012; 33:S35. DOI:10.1016/j.neurobiolaging.2012.01.099 · 4.85 Impact Factor
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    ABSTRACT: Given the recent and growing interest in the concepts of prodromal and presymptomatic Alzheimer disease, it is crucial to determine whether the presence of β-amyloid (Aβ) in the brain of asymptomatic elderly individuals is a pathologic condition associated with accelerated neuronal and synaptic loss. The aim of the present study was to assess whether Aβ influences the rate of atrophy in cognitively normal elderly individuals. Seventy-four healthy elderly individuals underwent an MRI scan and a 11C-Pittsburgh compound B (PiB) PET scan at baseline and a second MRI scan 18 months later. Voxel-wise analyses were performed using maps of annual rate of atrophy generated from the serial MRI scans, including comparison between individuals with high vs low neocortical PiB and correlation with baseline neocortical PiB. The rate of atrophy was significantly higher in the normal elderly individuals with high PiB compared with those with low PiB and was significantly correlated with baseline neocortical PiB, with the highest significance in the temporal neocortex and the posterior cingulate cortex. Our findings show that the presence of Aβ in the brain, known to occur in about one-third of asymptomatic elderly individuals, is actually a pathologic state associated with accelerated atrophy. They also suggest that therapy aimed to reduce the neurodegenerative process should be commenced in presymptomatic individuals with high PiB.
    Neurology 02/2012; 78(7):477-84. DOI:10.1212/WNL.0b013e318246d67a · 8.30 Impact Factor
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    ABSTRACT: Brain amyloid imaging using positron emission tomography (PET) is of increasing importance in the premortem evaluation of dementias, particularly in relation to Alzheimer disease (AD). The purpose of this study was to explore the premortem diagnostic utility of (11)C-PiB PET in sporadic Creutzfeldt-Jakob disease (CJD). Two patients, 72 and 59 years old, underwent evaluation for rapidly progressive cognitive decline, dying after illness durations of 5 and 7 months, respectively. As part of their comprehensive assessment, (18)F-FDG PET and (11)C-PiB PET studies were performed approximately 2-4 weeks prior to death, and the brain regional distributions compared with those from cohorts of healthy controls (HC) and AD patients. Routine investigations, including brain MRI scans, revealed changes typical of sporadic CJD, with the diagnosis confirmed at autopsy in both patients. The (18)F-FDG PET showed global hypometabolism in one patient and thalamic and frontal hypometabolism with unexpected hypermetabolism in the dentate nuclei of the cerebellum in the other. Neither patient displayed cerebral cortical (11)C-PiB PET retention above the levels observed in HC. No grey-matter (11)C-PiB retention was observed in two pathologically confirmed cases of typical sporadic CJD. We speculate that low PrP plaque density and small plaque size, as well as a relatively low affinity of the radioligand, explain the absence of (11)C-PiB retention. More studies to validate this hypothesis are warranted.
    Journal of neurology, neurosurgery, and psychiatry 04/2009; 80(9):998-1001. DOI:10.1136/jnnp.2008.171496 · 4.87 Impact Factor
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    ABSTRACT: Approximately 30% of healthy persons aged over 75 years show Abeta deposition at autopsy. It is postulated that this represents preclinical Alzheimer's disease (AD). We evaluated the relationship between Abeta burden as assessed by PiB PET and cognitive decline in a well-characterized, non-demented, elderly cohort. PiB PET studies and cognitive tests were performed on 34 elderly participants (age 73+/-6) from the longitudinal Melbourne Healthy Aging Study (MHAS). Subjects were classified as being cognitively 'stable' or 'declining' by an independent behavioural neurologist based on clinical assessment and serial word-list recall scores from the preceding 6-10 years. Decline was calculated from the slope of the word-list recall scores. Abeta burden was quantified using Standardized Uptake Value normalized to cerebellar cortex. Ten subjects were clinically classified as declining. At the time of the PET scans, three of the declining subjects had mild cognitive impairment, one had AD, and six were declining but remained within the normal range for age on cognitive tests. Declining subjects were much more likely to show cortical PiB binding than stable subjects (70% vs. 17%, respectively). Neocortical Abeta burden correlated with word-list recall slopes (r=-0.78) and memory function (r=-0.85) in the declining group. No correlations were observed in the stable group. Abeta burden correlated with incident memory impairment and the rate of memory decline in the non-demented ageing population. These observations suggest that neither memory decline nor Abeta deposition are part of normal ageing and likely represent preclinical AD. Further longitudinal observations are required to confirm this hypothesis.
    Neuropsychologia 02/2008; 46(6):1688-97. DOI:10.1016/j.neuropsychologia.2008.02.008 · 3.45 Impact Factor
  • Medical Physics 06/2007; 34(6). DOI:10.1118/1.2760483 · 3.01 Impact Factor
  • BJU International 03/2006; 97:10-10. DOI:10.1111/j.1464-410X.2006.06085_34.x · 3.13 Impact Factor
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    ABSTRACT: A non-invasive arterial monitor (NIAM) is being developed as an alternative to invasive arterial sampling to measure the input function of radiotracer uptake in PET patients. NIAM consists of dual Bismuth Germanate (BGO)-block detectors. The output was digitized at 500 MHz, and then processed to generate energy, timing and position information. System matrices were calculated for a range of geometries, allowing iterative reconstruction of tomographic images. Countrate efficiency was measured as 4.8cps/(kBq/ml) and countrate linearity was confirmed up to 330kBq/ml. The coincidence time resolution was measured using two techniques; a digital Constant Fraction Discriminator (CFD) and a Parametric Waveform Analysis (PWA). The resulting time-resolutions were; tCFD = 7.8ns and tPWA = 5.7ns. Spatial resolution was measured, both parallel (Deltax,y) and orthogonal (Deltaz) to the detector faces. At 140mm block separation, the measured resolution was Deltax,y = 6mm and Deltaz = 21mm. The system was simulated using the Geant4 Application for Tomographic Emission (GATE) to compare measured- vs. simulated-performance. After the dual-block validation of GATE, the performance characteristics of a simulated quad-block system were investigated.
    Nuclear Science Symposium Conference Record, 2006. IEEE; 01/2006