Medicine (Austin & Northern Health) - Research Publications

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    Trajectories of depressive and anxiety symptoms in older adults: a 6-year prospective cohort study
    Holmes, SE ; Esterlis, I ; Mazure, CM ; Lim, YY ; Ames, D ; Rainey-Smith, S ; Fowler, C ; Ellis, K ; Martins, RN ; Salvado, O ; Dore, V ; Villemagne, VL ; Rowe, CC ; Laws, SM ; Masters, CL ; Pietrzak, RH ; Maruff, P (WILEY, 2018-02)
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    Constructing longitudinal disease progression curves using sparse, short-term individual data with an application to Alzheimer's disease
    Budgeon, CA ; Murray, K ; Turlach, BA ; Baker, S ; Villemagne, VL ; Burnham, SC (WILEY, 2017-07-30)
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    Tau imaging with [18F]THK-5351 in progressive supranuclear palsy
    Ishiki, A ; Harada, R ; Okamura, N ; Tomita, N ; Rowe, CC ; Villemagne, VL ; Yanai, K ; Kudo, Y ; Arai, H ; Furumoto, S ; Tashiro, M ; Furukawa, K (WILEY-BLACKWELL, 2017-01)
    BACKGROUND AND PURPOSE: Visualization of pathogenic protein aggregates is crucial to elucidate pathomechanisms and to make an accurate diagnosis in many neurodegenerative conditions. Aggregates of the microtubule-binding protein, tau, are one of the most important pathogenic molecules in neurodegenerative disorders. Progressive supranuclear palsy (PSP) is characterized by the deposition of tau proteins in some specific area such as the basal ganglia and brainstem. We tried to detect tau lesions in the brains of living patients with PSP with a novel positron emission tomography (PET) tracer, [18 F]THK-5351, which we have recently developed. METHODS: Paraffin-embedded brain sections of the patients with PSP were used for autoradiography with [3 H]THK-5351 and immunohistochemistry. Nine healthy controls, 13 patients with Alzheimer's disease and three patients with PSP participated in this PET study with [18 F]THK-5351. To detect amyloid-β deposition, PET imaging with Pittsburgh compound B was also performed. RESULTS: Autoradiography in the brain sections of patients with PSP demonstrated [3 H]THK-5351 binding to tau deposits with a high selectivity. Although patients with PSP exhibited no remarkable [18 F]THK-5351 retention in the temporal cortex, significantly higher tracer retention was observed in the globus pallidus and midbrain. In contrast, amyloid imaging with Pittsburgh compound B showed no remarkable accumulation in the cerebral cortex of PSP. CONCLUSIONS: We conclude that [18 F]THK-5351 PET can potentially be used to detect the regional brain distribution of tau lesions in PSP, thereby facilitating the differential diagnosis of neurodegenerative disorders associated with tau protein.
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    Cerebrovascular disease, Alzheimer's disease biomarkers and longitudinal cognitive decline
    Yates, PA ; Villemagne, VL ; Ames, D ; Masters, CL ; Martins, RN ; Desmond, P ; Burnham, S ; Maruff, P ; Ellis, KA ; Rowe, CC (WILEY-BLACKWELL, 2016-06)
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    Amyloid burden and incident depressive symptoms in cognitively normal older adults
    Harrington, KD ; Gould, E ; Lim, YY ; Ames, D ; Pietrzak, RH ; Rembach, A ; Rainey-Smith, S ; Martins, RN ; Salvado, O ; Villemagne, VL ; Rowe, CC ; Masters, CL ; Maruff, P (WILEY, 2017-04)
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    Prevalence of amyloid-β pathology in distinct variants of primary progressive aphasia
    Bergeron, D ; Gorno-Tempini, ML ; Rabinovici, GD ; Santos-Santos, MA ; Seeley, W ; Miller, BL ; Pijnenburg, Y ; Keulen, MA ; Groot, C ; van Berckel, BNM ; van der Flier, WM ; Scheltens, P ; Rohrer, JD ; Warren, JD ; Schott, JM ; Fox, NC ; Sanchez-Valle, R ; Grau-Rivera, O ; Gelpi, E ; Seelaar, H ; Papma, JM ; van Swieten, JC ; Hodges, JR ; Leyton, CE ; Piguet, O ; Rogalski, EJ ; Mesulam, MM ; Koric, L ; Nora, K ; Pariente, J ; Dickerson, B ; Mackenzie, IR ; Hsiung, G-YR ; Belliard, S ; Irwin, DJ ; Wolk, DA ; Grossman, M ; Jones, M ; Harris, J ; Mann, D ; Snowden, JS ; Chrem-Mendez, P ; Calandri, IL ; Amengual, AA ; Miguet-Alfonsi, C ; Magnin, E ; Magnani, G ; Santangelo, R ; Deramecourt, V ; Pasquier, F ; Mattsson, N ; Nilsson, C ; Hansson, O ; Keith, J ; Masellis, M ; Black, SE ; Matias-Guiu, JA ; Cabrera-Martin, M-N ; Paquet, C ; Dumurgier, J ; Teichmann, M ; Sarazin, M ; Bottlaender, M ; Dubois, B ; Rowe, CC ; Villemagne, VL ; Vandenberghe, R ; Granadillo, E ; Teng, E ; Mendez, M ; Meyer, PT ; Frings, L ; Lleo, A ; Blesa, R ; Fortea, J ; Seo, SW ; Diehl-Schmid, J ; Grimmer, T ; Frederiksen, KS ; Sanchez-Juan, P ; Chetelat, G ; Jansen, W ; Bouchard, RW ; Laforce, R ; Visser, PJ ; Ossenkoppele, R (WILEY, 2018-11)
    OBJECTIVE: To estimate the prevalence of amyloid positivity, defined by positron emission tomography (PET)/cerebrospinal fluid (CSF) biomarkers and/or neuropathological examination, in primary progressive aphasia (PPA) variants. METHODS: We conducted a meta-analysis with individual participant data from 1,251 patients diagnosed with PPA (including logopenic [lvPPA, n = 443], nonfluent [nfvPPA, n = 333], semantic [svPPA, n = 401], and mixed/unclassifiable [n = 74] variants of PPA) from 36 centers, with a measure of amyloid-β pathology (CSF [n = 600], PET [n = 366], and/or autopsy [n = 378]) available. The estimated prevalence of amyloid positivity according to PPA variant, age, and apolipoprotein E (ApoE) ε4 status was determined using generalized estimating equation models. RESULTS: Amyloid-β positivity was more prevalent in lvPPA (86%) than in nfvPPA (20%) or svPPA (16%; p < 0.001). Prevalence of amyloid-β positivity increased with age in nfvPPA (from 10% at age 50 years to 27% at age 80 years, p < 0.01) and svPPA (from 6% at age 50 years to 32% at age 80 years, p < 0.001), but not in lvPPA (p = 0.94). Across PPA variants, ApoE ε4 carriers were more often amyloid-β positive (58.0%) than noncarriers (35.0%, p < 0.001). Autopsy data revealed Alzheimer disease pathology as the most common pathologic diagnosis in lvPPA (76%), frontotemporal lobar degeneration-TDP-43 in svPPA (80%), and frontotemporal lobar degeneration-TDP-43/tau in nfvPPA (64%). INTERPRETATION: This study shows that the current PPA classification system helps to predict underlying pathology across different cohorts and clinical settings, and suggests that age and ApoE genotype should be considered when interpreting amyloid-β biomarkers in PPA patients. Ann Neurol 2018;84:737-748.
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    Aβ Imaging: feasible, pertinent, and vital to progress in Alzheimer's disease
    Villemagne, VL ; Klunk, WE ; Mathis, CA ; Rowe, CC ; Brooks, DJ ; Hyman, BT ; Ikonomovic, MD ; Ishii, K ; Jack, CR ; Jagust, WJ ; Johnson, KA ; Koeppe, RA ; Lowe, VJ ; Masters, CL ; Montine, TJ ; Morris, JC ; Nordberg, A ; Petersen, RC ; Reiman, EM ; Selkoe, DJ ; Sperling, RA ; Van Laere, K ; Weiner, MW ; Drzezga, A (SPRINGER, 2012-02)
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    Clinical Profile of PiB-Positive Corticobasal Syndrome
    Burrell, JR ; Hornberger, M ; Villemagne, VL ; Rowe, CC ; Hodges, JR ; Tractenberg, RE (PUBLIC LIBRARY SCIENCE, 2013-04-05)
    BACKGROUND: Corticobasal syndrome (CBS) is a multifaceted neurodegenerative disorder characterized by a combination of motor and cognitive deficits. Several different pathological entities, including Alzheimer's pathology, have been described in association with CBS. The present study aimed to establish clinical, neuropsychological, and neuroimaging features that could be useful in the distinction of CBS due to AD pathology from other CBS cases in life based on [(11)C] Pittsburgh Compound B positron emission tomography (PiB-PET) status. METHODS: Patients with CBS were prospectively recruited from a specialized cognitive disorders clinic. All patients underwent detailed clinical and neuropsychological assessment, with structural imaging using voxel-based analysis of magnetic resonance imaging. Alzheimer's pathology was detected using PiB-PET imaging, and PiB-positive and PiB-negative groups were compared. RESULTS: Fourteen CBS patients meeting defined criteria were included (7 male, 7 female; mean age 66.1+/-6.9 years; median symptom duration was 35.5+/-22.6 months) and compared to 20 matched control subjects. Of the 14 patients, 4 were PiB-positive and 10 PiB-negative. There were no significant differences between PiB-positive and PiB-negative CBS patients in age, gender, education, symptom duration, or motor features. PiB-positive patients had greater visuospatial deficits, a higher rate of sentence repetition impairment, and more functional decline. Voxel-based morphometry analyses demonstrated extensive peri-insular and post-central atrophy in both groups, but PiB-positive patients had atrophy that extended to include the posterior part of the left superior temporal gyrus. CONCLUSIONS: Visuospatial function, aspects of language, and the pattern of cerebral atrophy may be useful in distinguishing patients with CBS due to underlying AD pathology.
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    Imago Mundi, Imago AD, Imago ADNI
    Villemagne, VL ; Kim, SY ; Rowe, CC ; Iwatsubo, T (BMC, 2014)
    Since the launch in 2003 of the Alzheimer's Disease Neuroimaging Initiative (ADNI) in the USA, ever growing, similarly oriented consortia have been organized and assembled around the world. The various accomplishments of ADNI have contributed substantially to a better understanding of the underlying physiopathology of aging and Alzheimer's disease (AD). These accomplishments are basically predicated in the trinity of multimodality, standardization and sharing. This multimodality approach can now better identify those subjects with AD-specific traits that are more likely to present cognitive decline in the near future and that might represent the best candidates for smaller but more efficient therapeutic trials - trials that, through gained and shared knowledge, can be more focused on a specific target or a specific stage of the disease process. In summary, data generated from ADNI have helped elucidate some of the pathophysiological mechanisms underpinning aging and AD pathology, while contributing to the international effort in setting the groundwork for biomarker discovery and establishing standards for early diagnosis of AD.
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    Basal forebrain atrophy correlates with amyloid β burden in Alzheimer's disease
    Kerbler, GM ; Fripp, J ; Rowe, CC ; Villemagne, VL ; Salvado, O ; Rose, S ; Coulson, EJ (ELSEVIER SCI LTD, 2015)
    The brains of patients suffering from Alzheimer's disease (AD) have three classical pathological hallmarks: amyloid-beta (Aβ) plaques, tau tangles, and neurodegeneration, including that of cholinergic neurons of the basal forebrain. However the relationship between Aβ burden and basal forebrain degeneration has not been extensively studied. To investigate this association, basal forebrain volumes were determined from magnetic resonance images of controls, subjects with amnestic mild cognitive impairment (aMCI) and AD patients enrolled in the longitudinal Alzheimer's Disease Neuroimaging Initiative (ADNI) and Australian Imaging, Biomarkers and Lifestyle (AIBL) studies. In the AIBL cohort, these volumes were correlated within groups to neocortical gray matter retention of Pittsburgh compound B (PiB) from positron emission tomography images as a measure of Aβ load. The basal forebrain volumes of AD and aMCI subjects were significantly reduced compared to those of control subjects. Anterior basal forebrain volume was significantly correlated to neocortical PiB retention in AD subjects and aMCI subjects with high Aβ burden, whereas posterior basal forebrain volume was significantly correlated to neocortical PiB retention in control subjects with high Aβ burden. Therefore this study provides new evidence for a correlation between neocortical Aβ accumulation and basal forebrain degeneration. In addition, cluster analysis showed that subjects with a whole basal forebrain volume below a determined cut-off value had a 7 times higher risk of having a worse diagnosis within ~18 months.