ORCID Profile
0000-0003-3910-2453
Current Organisations
Austin Health
,
Florey Institute of Neuroscience and Mental Health
,
University of Melbourne
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Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-09-2022
DOI: 10.1212/WNL.0000000000200857
Abstract: Traumatic brain injury (TBI) has been promoted as a risk factor for Alzheimer disease (AD). There is evidence of elevated β-amyloid (Aβ) and tau, the pathologic hallmarks of AD, immediately following TBI. It is not clear whether Aβ and tau remain elevated in the chronic period. To address this issue, we assessed Aβ and tau burden in long-term TBI survivors and healthy controls using PET imaging. Using a cross-sectional design, we recruited in iduals following a single moderate to severe TBI at least 10 years previously from an inpatient rehabilitation program. A demographically similar healthy control group was recruited from the community. PET data were acquired using 18 F-NAV4694 (Aβ) and 18 F-MK6240 (tau) tracers. Aβ deposition was quantified using the Centiloid scale. Tau deposition was quantified using the standardized uptake value ratio (SUVR) in 4 regions of interest (ROIs). As a secondary measure, PET scans were also visually read as positive or negative. We examined PET data in relation to time since injury and age at injury. PET data were analyzed in a series of regression analyses. The s le comprised 87 in iduals with TBI (71.3% male 28.7% female mean 57.53 years, SD 11.53) and 59 controls (59.3% male 40.7% female mean 60.34 years, SD 11.97). In iduals with TBI did not have significantly higher 18 F-NAV4694 Centiloid values ( p = 0.067) or 18 F-MK6240 tau SUVRs in any ROI ( p ≤ 0.001 SUVR greater for controls). Visual assessment was consistent with the quantification in iduals with TBI were not more likely than controls to have a positive Aβ ( p = 0.505) or tau scan ( p = 0.221). No associations were identified for Aβ or tau burden with time since injury ( p = 0.057 to 0.332) or age at injury. A single moderate to severe TBI was not associated with higher burden of Aβ or tau pathologies in the chronic period relative to healthy controls. Aβ and tau burden did not show a significant increase with years since injury, and burden did not appear to be greater for those who were older at the time of injury.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-02-2022
DOI: 10.1212/WNL.0000000000200118
Abstract: This prospective study sought to determine the association of modifiable/nonmodifiable components included in the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) risk score with hippoc al volume (HV) loss and episodic memory (EM) decline in cognitively normal (CN) older adults classified as brain β-amyloid (Aβ) negative (Aβ−) or positive (Aβ+). Australian Imaging, Biomarkers and Lifestyle study participants (age 58–91 years) who completed ≥2 neuropsychological assessments and a brain Aβ PET scan (n = 592) were included in this study. We computed the CAIDE risk score (age, sex, APOE ε4 status, education, hypertension, body mass index [BMI], hypercholesterolemia, physical inactivity) and a modifiable CAIDE risk score (CAIDE-MR education, hypertension, BMI, hypercholesterolemia, physical inactivity) for each participant. Aβ+ was classified using Centiloid . Linear mixed models assessed interactions between each CAIDE score, Aβ group, and time on HV loss and EM decline. Age, sex, and APOE ε4 were included as separate predictors in CAIDE-MR models to assess differential associations. Exploratory analyses examined relationships between in idual modifiable risk factors and outcomes in Aβ− cognitively normal (CN) adults. We observed a significant Aβ group × CAIDE × time interaction on HV loss (β [SE] = –0.04 [0.01] p 0.000) but not EM decline (β [SE] = –2.33 [9.96] p = 0.98). Decomposition revealed a significant CAIDE × time interaction in Aβ+ participants only. When modifiable/nonmodifiable CAIDE components were considered separately, we observed a significant Aβ group × CAIDE-MR × time interaction on EM decline only (β [SE] = 3.03 [1.18] p = 0.01). A significant CAIDE-MR score × time interaction was observed in Aβ− participants only. Significant interactions between APOE ε4 and age × time on HV loss and EM decline were observed in both groups. Exploratory analyses in Aβ− CN participants revealed a significant interaction between BMI × time on EM decline (β [SE] = –3.30 [1.43] p = 0.02). These results are consistent with studies showing that increasing age and APOE ε4 are associated with increased rates of HV loss and EM decline. In Aβ− CN adults, lower prevalence of modifiable cardiovascular risk factors was associated with less HV loss and EM decline over ∼10 years, suggesting interventions to reduce modifiable cardiovascular risk factors could be beneficial in this group.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-07-2023
DOI: 10.1212/WNL.0000000000207370
Abstract: Enlarged perivascular spaces (ePVS) have been identified as a key signature of glymphatic system dysfunction in neurologic conditions. The incidence and clinical implications of ePVS after traumatic brain injury (TBI) are not yet understood. We investigated whether in iduals with chronic moderate-to-severe TBI had an increased burden of ePVS and whether ePVS burden is modulated by the presence of focal lesions, older brain age, and poorer sleep quality. We examined whether an increased burden of ePVS was associated with poorer cognitive and emotional outcomes. Using a cross-sectional design, participants with a single moderate-to-severe chronic TBI (sustained ≥10 years ago) were recruited from an inpatient rehabilitation program. Control participants were recruited from the community. Participants underwent 3T brain MRI, neuropsychological assessment, and clinical evaluations. ePVS burden in white matter was quantified using automated segmentation. The relationship between the number of ePVS, group membership, focal lesions, brain age, current sleep quality, and outcome was modeled using negative binomial and linear regressions. This study included 100 participants with TBI (70% male mean age = 56.8 years) and 75 control participants (54.3% male mean age = 59.8 years). The TBI group had a significantly greater burden of ePVS (prevalence ratio rate [PRR] = 1.29, p = 0.013, 95% CI 1.05–1.57). The presence of bilateral lesions was associated with greater ePVS burden (PRR = 1.41, p = 0.021, 95% CI 1.05–1.90). There was no association between ePVS burden, sleep quality (PRR = 1.01, p = 0.491, 95% CI 0.98–1.048), and sleep duration (PRR = 1.03, p = 0.556, 95% CI 0.92–1.16). ePVS was associated with verbal memory (β = −0.42, p = 0.006, 95% CI −0.72 to −0.12), but not with other cognitive domains. The burden of ePVS was not associated with emotional distress (β = −0.70, p = 0.461, 95% CI −2.57 to 1.17) or brain age (PRR = 1.00, p = 0.665, 95% CI 0.99–1.02). TBI is associated with a greater burden of ePVS, especially when there have been bilateral brain lesions. ePVS was associated with reduced verbal memory performance. ePVS may indicate ongoing impairments in glymphatic system function in the chronic postinjury period.
Publisher: Cold Spring Harbor Laboratory
Date: 18-07-2023
DOI: 10.1101/2023.07.16.23292733
Abstract: The standardized uptake value ratio (SUVR) is used to measure Aβ uptake in PET images of the brain. Variations in PET scanner technologies and image reconstruction techniques can lead to variability in images acquired from different scanners. This poses a challenge for Aβ-PET studies conducted across multiple centers. The aim of harmonization is to achieve consistent Aβ-PET measurements across scanners. In this study, the procedure of matching the spatial resolution of a barrel phantom measured in each PET scanner is proposed as a method of Aβ-PET harmonization, validated using subject data. Three different PET scanners were used: the Siemens Biograph Vision 600, Siemens Biograph mCT, and Philips Gemini TF64. A total of five, eight, and five subjects were each scanned twice with [ 18 F]-NAV4694 across Vision-mCT, mCT-Philips, and Vision-Philips scanner pairs. The Vision and mCT scans were reconstructed using various iterations, subsets, and post-reconstruction Gaussian smoothing, while one reconstruction configuration was used for the Philips scans. The full-width at half-maximum (FWHM) of each reconstruction configuration was calculated using [ 18 F]-filled barrel phantom scans with the SNMMI phantom analysis toolkit. Regional SUVRs were calculated from 72 brain regions using the AAL3 atlas for each subject and reconstruction configuration. Statistical similarity between SUVRs was assessed using paired (within subject) t-tests for each pair of reconstructions across scanners the higher the p-value, the greater the similarity between the SUVRs. maximal statistical similarity (i.e., p -value) between regional SUVRs was achieved using a 4.10 mm FWHM Vision reconstruction with a 4.30 mm FWHM mCT reconstruction. maximal statistical similarity between regional SUVRs was achieved using an 8.2 mm FWHM Philips reconstruction with a 9.35 mm FWHM mCT reconstruction. a 9.1 mm FWHM Vision reconstruction had maximum statistical similarity with regional SUVRs from an 8.2mm FWHM Philips reconstruction. Reconstruction pairs that maximized statistical similarity, and supported a null hypothesis of being drawn from the same distribution, were selected as harmonised for each scanner pair. Using data obtained from three sets of participants, each scanned on a different pair of PET scanners, using reconstruction configurations with matched barrel phantom spatial resolutions, we have demonstrated that Aβ-PET quantitation can be harmonised across scanners, producing SUVR values statistically likely to be drawn from the same distribution. This finding is encouraging for the use of different PET scanners in multi-centre trials, or updates during longitudinal studies.
Publisher: Research Square Platform LLC
Date: 09-02-2023
DOI: 10.21203/RS.3.RS-2553800/V1
Abstract: Background: Plasma p217+tau has shown high concordance with cerebrospinal fluid (CSF) and positron emission tomography (PET) measures of amyloid-β (Aβ) and tau in Alzheimer’s Disease (AD). However, its association with longitudinal cognition and comparative performance to PET Aβ and tau in predicting cognitive decline are unknown. Objectives: To evaluate whether p217+tau can predict the rate of cognitive decline observed over two-year average follow-up and compare this to prediction based on Aβ ( 18 F-NAV4694) and tau ( 18 F-MK6240) PET. We also explored the s le size required to detect a 30% slowing in cognitive decline in a 2-year trial and selection test cost using p217+tau (pT+) as compared to PET Aβ (A+) and tau (T+) with and without p217+tau pre-screening. Design: A prospective observational cohort study. Setting: Participants of the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL) and Australian Dementia Network (ADNeT). Participants: 153 cognitively unimpaired (CU) and 50 cognitively impaired (CI) in iduals. Measurements: Baseline p217+tau Simoa® assay, 18 F-MK6240 tau-PET and 18 F-NAV4694 Aβ-PET with neuropsychological follow-up (MMSE, CDR-SB, AIBL-PACC) over 2.4 ± 0.8 years. Results: In CI, p217+tau was a significant predictor of change in MMSE (β = -0.55, p 0.001) and CDR-SB (β =0.61, p 0.001) with an effect size similar to Aβ Centiloid (MMSE β = -0.48, p = 0.002 CDR-SB β = 0.43, p = 0.004) and meta-temporal (MetaT) tau SUVR (MMSE: β = -0.62, p 0.001 CDR-SB: β = 0.65, p 0.001). In CU, only MetaT tau SUVR was significantly associated with change in AIBL-PACC (β = -0.22, p = 0.008). Screening pT+ CI participants into a trial could lead to 24% reduction in s le size compared to screening with PET for A+ and 6-13% compared to screening with PET for T+ (different regions). This would translate to an 81-83% biomarker test cost-saving assuming the p217+tau test cost one-fifth of a PET scan. In a trial requiring PET A+ or T+, p217+tau pre-screening followed by PET in those who were pT+ would cost more in the CI group, compared to 26-38% biomarker test cost-saving in the CU. Conclusions: Substantial cost reduction can be achieved using p217+tau alone to select participants with MCI or mild dementia for a clinical trial designed to slow cognitive decline over two years, compared to participant selection by PET. In pre-clinical AD trials, p217+tau provides significant cost-saving if used as a pre-screening measure for PET A+ or T+ but in MCI/mild dementia trials this may add to cost both in testing and in the increased number of participants needed for testing.
Publisher: Cold Spring Harbor Laboratory
Date: 03-07-2023
DOI: 10.1101/2023.07.03.23292155
Abstract: Amyloid beta (Aβ) accumulation in Alzheimer’s disease (AD) is typically measured using standardized uptake value ratio (SUVR) and the Centiloid scale (CL). The low spatial resolution of PET images is known to degrade quantitative metrics due to the partial volume effect (PVE). This paper examines the impact of spatial resolution, as determined by the reconstruction configuration, on the Aβ-PET quantitation in both cross-sectional and longitudinal data. Cross-sectional Study -89 subjects with [ 18 F]-florbetapir scans (44 Aβ-, 45 Aβ+) were reconstructed using 69 reconstruction configurations. For each reconstruction, Aβ SUVR was calculated and the spatial resolution was calculated as full-width-at-half-maximum (FWHM) using the barrel phantom method (Lodge et al , 2018). The change of SUVR and the effect size of the difference in SUVR between Aβ- and Aβ+ groups with FWHM were examined. Longitudinal study -79 subjects (46 Aβ-, 33 Aβ+) with three [ 18 F]-flutemetamol scans were analysed. All scans were reconstructed using low-, medium- and high-resolution reconstruction configurations and Aβ CLs were calculated. Since linear Aβ accumulation was assumed over a 10-year interval, for each reconstruction configuration, Aβ accumulation rate differences (ARD) between the second and first periods were calculated for all the subjects and compared. Zero ARD was used as a consistency metric. The number of Aβ-accumulators was also used to compare reconstruction configurations. Cross-sectional- SUVRs in both Aβ- and Aβ+ groups were impacted by the FWHM of the reconstruction method Aβ- SUVRs increased for FWHM ≥ 4.5 mm, while Aβ+ SUVRs decreased across the FWHM range. High-resolution reconstructions provided the best statistical separation between groups. Longitudinal study -In the Aβ-group, the median ARD of low-resolution reconstructed data was greater than zero whereas the ARDs of higher-resolution reconstructions were not significantly different to zero, indicating less consistent rates in the low-than the higher-resolution data. Higher-resolution reconstructions identified 10 additional Aβ-accumulators in the Aβ-group, resulting in a 22% increased group size compared to the low-resolution reconstructions. Higher-resolution reconstructions reduced the average CL values of the negative group by 12 points. High-resolution PET reconstructions, inherently less impacted by PVE, may improve Aβ-PET quantitation in both cross-sectional and longitudinal data. In the cross-sectional analysis, separation of Aβ groups’ SUVRs increased with spatial resolution. Longitudinal analysis showed better Aβ accumulation consistency in higher-resolution compared to low-resolution reconstructions. The identification of more Aβ-accumulators from the higher-resolution reconstruction may be helpful in early-stage AD therapies.
Publisher: Informa UK Limited
Date: 15-04-2022
DOI: 10.1080/09602011.2021.1914674
Abstract: This prospective controlled study examined long-term trajectories of neuropsychological performance in in iduals with traumatic brain injury (TBI) compared to healthy controls, and the impact of IQ, age at injury, time since injury, and injury severity on change over time. Fifty-three in iduals with moderate to severe TBI (60.37% male
Publisher: Cold Spring Harbor Laboratory
Date: 28-05-2020
DOI: 10.1101/2020.05.26.20114215
Abstract: Changes to lipid metabolism are tightly associated with the onset and pathology of Alzheimer’s disease (AD). Lipids are complex molecules comprising of many isomeric and isobaric species, necessitating detailed analysis to enable interpretation of biological significance. Our expanded targeted lipidomics platform (569 lipid species across 32 lipid (sub)classes) allows for detailed isomeric and isobaric lipid separation. We applied the methodology to examine plasma s les from the Australian Imaging, Biomarkers and Lifestyle flagship study of aging (AIBL, n = 1112) and serum from the Alzheimer’s Disease Neuroimaging Initiative (ADNI, n = 800) studies. Cross sectional analysis using both cohorts identified concordant unique peripheral signatures associated with AD. Specific pathways include sphingolipids, including G M3 gangliosides, where their acyl composition drove the major associations, and lipids previously associated with dysfunctional lipid metabolism in cardiometabolic disease including the phosphatidylethanolamine and triglyceride classes. Infomation derived from improved isomeric seperation highlighted pathway-specific changes with ether lipids including plasmalogens implicating perixosmal dysfunction in disease pathology. Longitudinal analysis revealed similar lipid signitures in both AIBL and ADNI cohorts with future disease onset. We utilised the two independent studies to train and validate multivariate lipid models that significantly improved disease classification and prediction. Together our results provide a holistic view of the lipidome and its relationship with AD using a comprehensive lipidomics approach, providing targets for further mechanistic investigation.
Publisher: JMIR Publications Inc.
Date: 26-05-2016
DOI: 10.2196/MHEALTH.5368
Publisher: Springer Science and Business Media LLC
Date: 04-03-2020
DOI: 10.1186/S13195-020-00587-5
Abstract: The Centiloid scale was developed to standardise the results of beta-amyloid (Aβ) PET. We aimed to determine the Centiloid unit (CL) thresholds for CERAD sparse and moderate-density neuritic plaques, Alzheimer’s disease neuropathologic change (ADNC) score of intermediate or high probability of Alzheimer’s Disease (AD), final clinicopathological diagnosis of AD, and expert visual read of a positive Aβ PET scan. Aβ PET results in CL for 49 subjects were compared with post-mortem findings, visual read, and final clinicopathological diagnosis. The Youden Index was used to determine the optimal CL thresholds from receiver operator characteristic (ROC) curves. A threshold of 20.1 CL (21.3 CL when corrected for time to death, AUC 0.97) yielded highest accuracy in detecting moderate or frequent plaque density while 10 CL was optimal for excluding neuritic plaque. The threshold for ADNC intermediate or high likelihood AD was 49.4 CL (AUC 0.98). Those cases with a final clinicopathological diagnosis of AD yielded a median CL result of 87.7 (IQR ± 42.2) with 94% 45 CL. Positive visual read agreed highly with results 26 CL. Centiloid values 10 accurately reflected the absence of any neuritic plaque and 20 CL indicated the presence of at least moderate plaque density, but approximately 50 CL or more best confirmed both neuropathological and clinicopathological diagnosis of Alzheimer’s disease.
Publisher: Wiley
Date: 24-08-2022
DOI: 10.1111/JNC.15681
Abstract: Cholesterol levels have been repeatedly linked to Alzheimer's Disease (AD), suggesting that high levels could be detrimental, but this effect is likely attributed to Low-Density Lipoprotein (LDL) cholesterol. On the other hand, High-Density Lipoproteins (HDL) cholesterol levels have been associated with reduced brain amyloidosis and improved cognitive function. However, recent findings have suggested that HDL-functionality, which depends upon the HDL-cargo proteins associated with HDL, rather than HDL levels, appears to be the key factor, suggesting a quality over quantity status. In this report, we have assessed the HDL-cargo (Cholesterol, ApoA-I, ApoA-II, ApoC-I, ApoC-III, ApoD, ApoE, ApoH, ApoJ, CRP, and SAA) in stable healthy control (HC), healthy controls who will convert to MCI/AD (HC-Conv) and AD patients (AD). Compared to HC we observed an increased cholesterol/ApoA-I ratio in AD and HC-Conv, as well as an increased ApoD/ApoA-I ratio and a decreased ApoA-II/ApoA-I ratio in AD. Higher cholesterol/ApoA-I ratio was also associated with lower cortical grey matter volume and higher ventricular volume, while higher ApoA-II/ApoA-I and ApoJ/ApoA-I ratios were associated with greater cortical grey matter volume (and for ApoA-II also with greater hippoc al volume) and smaller ventricular volume. Additionally, in a clinical status-independent manner, the ApoE/ApoA-I ratio was significantly lower in APOE ε4 carriers and lowest in APOE ε4 homozygous. Together, these data indicate that in AD patients the composition of HDL is altered, which may affect HDL functionality, and such changes are associated with altered regional brain volumetric data.
Publisher: BMJ
Date: 09-2020
DOI: 10.1136/BMJOPEN-2020-038312
Abstract: Cancer-related cognitive impairment (CRCI) is a distressing and disabling side-effect of cancer treatments affecting up to 75% of patients. For some patients, their cognitive impairment may be transient, but for a subgroup, these symptoms can be long-standing and have a major impact on the quality of life. This paper describes the protocol for a study: (1) to assess the feasibility of collecting longitudinal data on cognition via self-report, neuropsychological testing, peripheral markers of inflammation and neuroimaging and (2) to explore and describe patterns of cancer-related cognitive impairment over the course of treatment and recovery in patients with newly diagnosed, aggressive lymphoma undergoing standard therapy with curative intent. This is a prospective, longitudinal, feasibility study in which 30 newly diagnosed, treatment-naive patients with aggressive lymphoma will be recruited over a 12-month period. Patients will complete comprehensive assessments at three time points: baseline (time 1, pre-treatment) and two post-baseline follow-up assessments (time 2, mid-treatment and time 3, 6–8 weeks post-treatment completion). All patients will be assessed for self-reported cognitive difficulties and objective cognitive function using Stroop Colour and Word, Trail Making Test Part A and B, Hopkins Verbal Learning Test-Revised, Controlled Oral Word Association and Digit Span. Blood cell-based inflammatory markers and neuroimaging including a positron emission tomography (PET) with 18 F-labelled fluoro-2-deoxyglucose ( 18 F-FDG) and CT ( 18 F-FDG-PET/CT) and a MRI will explore potential inflammatory and neuroanatomical or functional mechanisms and biomarkers related to CRCI. The primary intent of analysis will be to assess the feasibility of collecting longitudinal data on cognition using subjective reports and objective tasks from patients during treatment and recovery for lymphoma. These data will inform the design of a larger-scale investigation into the patterns of cognitive change over the course of treatment and recovery, adding to an underexplored area of cancer survivorship research. Ethical approval has been granted by Austin Health Human Rights Ethics Committee (HREC) in Victoria Australia. Peer reviewed publications and conference presentations will report the findings of this novel study. Australian New Zealand Clinical Trials Registry (ACTRN12619001649101).
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-10-2023
Location: United States of America
Location: Australia
No related grants have been discovered for Christopher Rowe.