Medicine (Austin & Northern Health) - Research Publications

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Author: Desmond, Patricia × Author: Rowe, Christopher × End date: 2019 × Start date: 2016 ×

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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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    Metabolic patterns and seizure outcomes following anterior temporal lobectomy
    Cahill, V ; Sinclair, B ; Malpas, CB ; McIntosh, AM ; Chen, Z ; Vivash, LE ; O'Shea, MF ; Wilson, SJ ; Desmond, PM ; Berlangieri, SU ; Hicks, RJ ; Rowe, CC ; Morokoff, AP ; King, JA ; Fabinyi, GC ; Kaye, AH ; Kwan, P ; Berkovic, SF ; O'Brien, TJ (WILEY, 2019-02)
    OBJECTIVE: We investigated the relationship between the interictal metabolic patterns, the extent of resection of 18 F-fluorodeoxyglucose positron emission tomography (18 FDG-PET) hypometabolism, and seizure outcomes in patients with unilateral drug-resistant mesial temporal lobe epilepsy (MTLE) following anterior temporal lobe (TL) resection. METHODS: Eighty-two patients with hippocampal sclerosis or normal magnetic resonance imaging (MRI) findings, concordant 18 FDG-PET hypometabolism, and at least 2 years of postoperative follow-up were included in this 2-center study. The hypometabolic regions in each patient were identified with reference to 20 healthy controls (p < 0.005). The resected TL volume and the volume of resected TL PET hypometabolism (TLH) were calculated from the pre- and postoperative MRI scans coregistered with interictal 18 FDG-PET. RESULTS: Striking differences in metabolic patterns were observed depending on the lateralization of the epileptogenic TL. The extent of the ipsilateral TLH was significantly greater in left MTLE patients (p < 0.001), whereas right MTLE patients had significantly higher rates of contralateral (CTL) TLH (p = 0.016). In right MTLE patients, CTL hypometabolism was the strongest predictor of an unfavorable seizure outcome, associated with a 5-fold increase in the likelihood of seizure recurrence (odds ratio [OR] = 4.90, 95% confidence interval [CI] = 1.07-22.39, p = 0.04). In left MTLE patients, greater extent of resection of ipsilateral TLH was associated with lower rates of seizure recurrence (p = 0.004) in univariate analysis; however, its predictive value did not reach statistical significance (OR = 0.96, 95% CI = 0.90-1.02, p = 0.19). INTERPRETATION: The difference in metabolic patterns depending on the lateralization of MTLE may represent distinct epileptic networks in patients with right versus left MTLE, and can guide preoperative counseling and surgical planning. Ann Neurol 2019; 1-10 ANN NEUROL 2019;85:241-250.
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    Cerebral quantitative susceptibility mapping predicts amyloid-β-related cognitive decline
    Ayton, S ; Fazlollahi, A ; Bourgeat, P ; Raniga, P ; Ng, A ; Lim, YY ; Diouf, I ; Farquharson, S ; Fripp, J ; Ames, D ; Doecke, J ; Desmond, P ; Ordidge, R ; Masters, CL ; Rowe, CC ; Maruff, P ; Villemagne, VL ; Salvado, O ; Bush, AI (OXFORD UNIV PRESS, 2017-08)
    See Derry and Kent (doi:10.1093/awx167) for a scientific commentary on this article.The large variance in cognitive deterioration in subjects who test positive for amyloid-β by positron emission tomography indicates that convergent pathologies, such as iron accumulation, might combine with amyloid-β to accelerate Alzheimer's disease progression. Here, we applied quantitative susceptibility mapping, a relatively new magnetic resonance imaging method sensitive to tissue iron, to assess the relationship between iron, amyloid-β load, and cognitive decline in 117 subjects who underwent baseline magnetic resonance imaging and amyloid-β positron emission tomography from the Australian Imaging, Biomarkers and Lifestyle study (AIBL). Cognitive function data were collected every 18 months for up to 6 years from 100 volunteers who were either cognitively normal (n = 64) or diagnosed with mild cognitive impairment (n = 17) or Alzheimer's disease (n = 19). Among participants with amyloid pathology (n = 45), higher hippocampal quantitative susceptibility mapping levels predicted accelerated deterioration in composite cognition tests for episodic memory [β(standard error) = -0.169 (0.034), P = 9.2 × 10-7], executive function [β(standard error) = -0.139 (0.048), P = 0.004), and attention [β(standard error) = -0.074 (0.029), P = 0.012]. Deteriorating performance in a composite of language tests was predicted by higher quantitative susceptibility mapping levels in temporal lobe [β(standard error) = -0.104 (0.05), P = 0.036] and frontal lobe [β(standard error) = -0.154 (0.055), P = 0.006]. These findings indicate that brain iron might combine with amyloid-β to accelerate clinical progression and that quantitative susceptibility mapping could be used in combination with amyloid-β positron emission tomography to stratify individuals at risk of decline.