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John T. O'Brien

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7 papers

1 author row

YNICL Journal 2021 Journal Article

In vivo nucleus basalis of Meynert degeneration in mild cognitive impairment with Lewy bodies

Julia Schumacher
John-Paul Taylor
Calum A. Hamilton
Michael Firbank
Ruth A. Cromarty
Paul C. Donaghy
Gemma Roberts
Louise Allan

OBJECTIVES: To investigate in vivo degeneration of the cholinergic system in mild cognitive impairment with Lewy bodies (MCI-LB), we studied nucleus basalis of Meynert (NBM) volumes from structural MR images and its relation to EEG slowing and cognitive impairment. METHODS: We studied the NBM using structural MR images in 37 patients with MCI-LB, 34 patients with MCI with Alzheimer's disease (MCI-AD), and 31 healthy control participants. We also tested correlations between NBM volumes and measures of overall cognition and measures of EEG slowing in the MCI groups. RESULTS: Overall NBM volume was reduced in MCI-LB compared to controls with no significant difference between MCI-AD and controls or between the two MCI groups. The voxel-wise analysis revealed bilateral clusters of reduced NBM volume in MCI-LB compared to controls and smaller clusters in MCI-AD compared to controls. There was a significant association between overall NBM volume and measures of overall cognition in MCI-LB, but not in MCI-AD. In both MCI groups, reduced NBM volume was correlated with more severe EEG slowing. CONCLUSIONS: This study provides in vivo evidence that early cholinergic degeneration in DLB occurs at the MCI stage and is related to the severity of cognitive impairment. Furthermore, the results suggest that early EEG slowing in MCI-LB might be in part cholinergically driven. Importantly, these findings suggest an early cholinergic deficit in MCI-LB that may motivate further testing of the effectiveness of cholinesterase inhibitors in this group.

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YNICL Journal 2020 Journal Article

Correlation of microglial activation with white matter changes in dementia with Lewy bodies

Nicolas Nicastro
Elijah Mak
Guy B. Williams
Ajenthan Surendranathan
W Richard Bevan-Jones
Luca Passamonti
Patricia Vàzquez Rodrìguez
Li Su

C]-PK11195 binding in frontal, temporal, and occipital lobes. However, microglial activation was not significantly associated with grey matter changes. Our study suggests that increased microglial activation is associated with a relative preservation of white matter and cognition in DLB, positioning neuroinflammation as a potential early marker of DLB etio-pathogenesis.

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YNICL Journal 2019 Journal Article

Dynamic functional connectivity changes in dementia with Lewy bodies and Alzheimer's disease

Julia Schumacher
Luis R. Peraza
Michael Firbank
Alan J. Thomas
Marcus Kaiser
Peter Gallagher
John T. O'Brien
Andrew M. Blamire

We studied the dynamic functional connectivity profile of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) compared to controls, how it differs between the two dementia subtypes, and a possible relation between dynamic connectivity alterations and temporally transient clinical symptoms in DLB. Resting state fMRI data from 31 DLB, 29 AD, and 31 healthy control participants were analyzed using dual regression to determine between-network functional connectivity. Subsequently, we used a sliding window approach followed by k-means clustering and dynamic network analyses to study dynamic functional connectivity. Dynamic connectivity measures that showed significant group differences were tested for correlations with clinical symptom severity. Our results show that AD and DLB patients spent more time than controls in sparse connectivity configurations with absence of strong positive and negative connections and a relative isolation of motor networks from other networks. Additionally, DLB patients spent less time in a more strongly connected state and the variability of global brain network efficiency was reduced in DLB compared to controls. There were no significant correlations between dynamic connectivity measures and clinical symptom severity. An inability to switch out of states of low inter-network connectivity into more highly and specifically connected network configurations might be related to the presence of dementia in general as it was observed in both AD and DLB. In contrast, the loss of global efficiency variability in DLB might indicate the presence of an abnormally rigid brain network and the lack of economical dynamics, factors which could contribute to cognitive slowing and an inability to respond appropriately to situational demands.

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YNICL Journal 2018 Journal Article

A new visual rating scale for Ioflupane imaging in Lewy body disease

Jim J. Lloyd
George Petrides
Paul C. Donaghy
Sean J. Colloby
Johannes Attems
John T. O'Brien
Gemma Roberts
Alan J. Thomas

BACKGROUND: I-Ioflupane brain imaging is a recognised biomarker for dementia with Lewy bodies. It is usually assessed using a visual rating scale developed for Parkinson's disease, which may not be optimal for dementia with Lewy bodies, as patterns of dopaminergic loss can be different. OBJECTIVES: I-Ioflupane brain images in Lewy body disease that encompasses appearances seen in dementia with Lewy bodies, and validate this against autopsy diagnosis. METHODS: Four experienced observers developed and tested a new scale consisting of two metrics, reflecting overall loss and heterogeneity of loss. 66 subjects were used during development including clinical diagnoses of Alzheimer's disease (n = 14), Parkinson's disease (n = 9), Parkinson's disease dementia (n = 9), dementia with Lewy bodies (n = 15) and normal controls (n = 19). The scale was then tested on an independent group of 46 subjects with autopsy confirmed diagnosis: Alzheimer's disease (n = 11), Parkinson's disease (n = 3), Parkinson's disease dementia (n = 15), dementia with Lewy bodies (n = 12), normal controls (n = 4) and Frontotemporal dementia (n = 1). RESULTS: In the autopsy validation the sensitivity and specificity of the new scale for Lewy body disease was 97% and 100% respectively, compared with the standard scale which had the same sensitivity (97%), but lower specificity (80%). The new scale had excellent inter rater reliability (intra-class correlation coefficient 0.93). CONCLUSION: I-Ioflupane brain images. It demonstrated high accuracy in autopsy confirmed cases and offers advantages over the existing visual rating scale.

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YNICL Journal 2015 Journal Article

Longitudinal assessment of global and regional atrophy rates in Alzheimer's disease and dementia with Lewy bodies

Elijah Mak
Li Su
Guy B. Williams
Rosie Watson
Michael Firbank
Andrew M. Blamire
John T. O'Brien

Background & objective Percent whole brain volume change (PBVC) measured from serial MRI scans is widely accepted as a sensitive marker of disease progression in Alzheimer's disease (AD). However, the utility of PBVC in the differential diagnosis of dementia remains to be established. We compared PBVC in AD and dementia with Lewy bodies (DLB), and investigated associations with clinical measures. Methods 72 participants (14 DLBs, 25 ADs, and 33 healthy controls (HCs)) underwent clinical assessment and 3 Tesla T1-weighted MRI at baseline and repeated at 12 months. We used FSL-SIENA to estimate PBVC for each subject. Voxelwise analyses and ANCOVA compared PBVC between DLB and AD, while correlational tests examined associations of PBVC with clinical measures. Results AD had significantly greater atrophy over 1 year (1. 8%) compared to DLB (1. 0%; p = 0. 01) and HC (0. 9%; p < 0. 01) in widespread regions of the brain including periventricular areas. PBVC was not significantly different between DLB and HC (p = 0. 95). There were no differences in cognitive decline between DLB and AD. In the combined dementia group (AD and DLB), younger age was associated with higher atrophy rates (r = 0. 49, p < 0. 01). Conclusions AD showed a faster rate of global brain atrophy compared to DLB, which had similar rates of atrophy to HC. Among dementia subjects, younger age was associated with accelerated atrophy, reflecting more aggressive disease in younger people. PBVC could aid in differentiating between DLB and AD, however its utility as an outcome marker in DLB is limited.

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YNIMG Journal 2004 Journal Article

Comparing gray matter loss profiles between dementia with Lewy bodies and Alzheimer's disease using cortical pattern matching: diagnosis and gender effects

Martina Ballmaier
John T. O'Brien
Emma J. Burton
Paul M. Thompson
David E. Rex
Katherine L. Narr
Ian G. McKeith
Heather DeLuca

We used magnetic resonance imaging (MRI) and cortical pattern matching to map differences in cortical gray matter deficits between Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), and explored the possible influence of gender on these patterns. Twenty-nine patients with AD (age 77. 9 ± 5. 5), 16 patients with DLB (76. 4 ± 6. 7), and 38 controls (75. 3 ± 6. 8) were included. Dementia groups were matched for illness severity. Detailed spatial analyses of gray matter were conducted across the entire cerebral cortex by measuring local proportions of gray matter at thousands of homologous cortical surface locations in each subject and between diagnostic groups. To visualize regional changes, statistical differences were mapped at each cortical surface location in 3D. Main effects of diagnosis demonstrated prominent gray matter differences in orbitofrontal and temporal cortices, where AD exhibited the greatest deficits relative to DLB. Main effects of sex showed less gray matter in men within all group comparisons. Exploratory findings for sex by diagnosis interactions suggest greater gray matter loss in the anterior cingulate for men with AD, relative to controls, AD females, and individuals with DLB. Relative preservation of orbitofrontal cortices in addition to temporal structures may contribute to distinguishing DLB from AD. Further investigation of the influence of gender might provide a more comprehensive understanding of the pathophysiological differences underlying the two forms of dementia.

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YNIMG Journal 2004 Journal Article

The application of statistical parametric mapping to 123I-FP-CIT SPECT in dementia with Lewy bodies, Alzheimer's disease and Parkinson's disease

Sean J. Colloby
John T. O'Brien
John D. Fenwick
Michael J. Firbank
David J. Burn
Ian G. McKeith
E. David Williams

Dopaminergic loss can be visualised using 123I-FP-CIT single photon emission computed tomography (SPECT) in several disorders including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Most previous SPECT studies have adopted region of interest (ROI) methods for analysis, which are subjective and operator-dependent. The purpose of this study was to investigate differences in striatal binding of 123I-FP-CIT SPECT using the automated technique of statistical parametric mapping (SPM99) in subjects with DLB, Alzheimer's disease (AD), PD and healthy age-matched controls. This involved spatial normalisation of each subject's image to a customised template, followed by smoothing and intensity normalisation of each image to its corresponding mean occipital count per voxel. Group differences were assessed using a two-sample t test. Applying a height threshold of P ≤ 0. 05 corrected, the SPM{t} maps showed a significant bilateral reduced uptake in caudate, anterior and posterior putamen in DLB and PD subjects compared to AD subjects and controls. Significant reduction in binding was also observed bilaterally in the caudate nucleus in AD compared to controls. Striatal binding was indistinguishable between patients with DLB and PD. To investigate the usefulness of SPM as a decision aid in the evaluation of visually rated normal and abnormal patterns of uptake, receiver operator characteristic (ROC) curve analysis was performed using data from single-subject SPMs. The areas under the ROC curves were greater than 0. 92, demonstrating comparable discriminatory power with visual rating. The automated voxel-based approach is a viable alternative to the subjective and often time-consuming method of ROI and, in addition, may have the potential to differentiate between normal and abnormal patterns of uptake in a manner similar to visual inspection.

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