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3. Neuroanatomical and cognitive correlates of visual hallucinations in Parkinson’s disease and dementia with Lewy bodies: Voxel-based morphometry and neuropsychological meta-analysis

Author

Pezzoli, Stefania, Sánchez-Valle, Raquel, Solanes, Aleix, Kempton, Matthew J, Bandmann, Oliver, Shin, Jae Il, Cagnin, Annachiara, Goldman, Jennifer G, Merkitch, Doug, Firbank, Michael J, Taylor, John-Paul, Pagonabarraga, Javier, Kulisevsky, Jaime, Blanc, Frederic, Verdolini, Norma, Venneri, Annalena, and Radua, Joaquim

Subjects
Biomedical and Clinical Sciences, Health Sciences, Mental Health, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, Acquired Cognitive Impairment, Brain Disorders, Parkinson's Disease, Neurosciences, Aging, 2.1 Biological and endogenous factors, Aetiology, Neurological, Cognition, Hallucinations, Humans, Lewy Body Disease, Magnetic Resonance Imaging, Neuropsychological Tests, Parkinson Disease, Lewy body disease, Visual hallucinations, Dementia with Lewy bodies, Meta-analysis, VBM, MRI, Grey matter volume, Neuropsychology, Memory, Parkinson's disease, Parkinson’s disease, Medical and Health Sciences, Psychology and Cognitive Sciences, Behavioral Science & Comparative Psychology, Biomedical and clinical sciences, Health sciences
Abstract

Visual hallucinations (VH) are common in Parkinson's disease and dementia with Lewy bodies, two forms of Lewy body disease (LBD), but the neural substrates and mechanisms involved are still unclear. We conducted meta-analyses of voxel-based morphometry (VBM) and neuropsychological studies investigating the neuroanatomical and cognitive correlates of VH in LBD. For VBM (12 studies), we used Seed-based d Mapping with Permutation of Subject Images (SDM-PSI), including statistical parametric maps for 50% of the studies. For neuropsychology (35 studies), we used MetaNSUE to consider non-statistically significant unreported effects. VH were associated with smaller grey matter volume in occipital, frontal, occipitotemporal, and parietal areas (peak Hedges' g -0.34 to -0.49). In patients with Parkinson's disease without dementia, VH were associated with lower verbal immediate memory performance (Hedges' g -0.52). Both results survived correction for multiple comparisons. Abnormalities in these brain regions might reflect dysfunctions in brain networks sustaining visuoperceptive, attention, and executive abilities, with the latter also being at the basis of poor immediate memory performance.

Published
2021

13. White matter changes in the cholinergic system in Alzheimer’s disease and dementia with Lewy bodies

Author

Schumacher, Julia, primary, Ray, Nicola, additional, Hamilton, Calum Alexander, additional, Bergamino, Maurizio, additional, Donaghy, Paul C, additional, Firbank, Michael J, additional, Watson, Rosie, additional, Roberts, Gemma, additional, Allan, Louise M, additional, Barnett, Nicola, additional, O'Brien, John T, additional, Thomas, Alan J, additional, and Taylor, John‐Paul, additional

Published
2023
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14. Promises and Challenges of Blood Based Biomarkers of Alzheimer’s Disease and Neurodegeneration in Mild Cognitive Impairment: Importance of Non‐Alzheimer’s Aetiologies

Author

Hamilton, Calum Alexander, primary, O'Brien, John T, additional, Heslegrave, Amanda, additional, Laban, Rhiannon, additional, Donaghy, Paul C, additional, Durcan, Rory, additional, Lawley, Sarah, additional, Barnett, Nicola, additional, Roberts, Gemma, additional, Firbank, Michael J, additional, Taylor, John‐Paul, additional, Zetterberg, Henrik, additional, and Thomas, Alan J, additional

Published
2023
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18. Functional connectivity in Lewy body disease with visual hallucinations.

Author

Firbank, Michael J., Collerton, Daniel, Morgan, Katrina daSilva, Schumacher, Julia, Donaghy, Paul C., O'Brien, John T., Thomas, Alan, and Taylor, John‐Paul

Subjects
*FUNCTIONAL connectivity, *DEFAULT mode network, *HALLUCINATIONS, *VISUAL cortex, *NETWORK performance
Abstract

Background and purpose: Visual hallucinations are a common, potentially distressing experience of people with Lewy body disease (LBD). The underlying brain changes giving rise to visual hallucinations are not fully understood, although previous models have posited that alterations in the connectivity between brain regions involved in attention and visual processing are critical. Methods: Data from 41 people with LBD and visual hallucinations, 48 with LBD without visual hallucinations and 60 similarly aged healthy comparator participants were used. Connections were investigated between regions in the visual cortex and ventral attention, dorsal attention and default mode networks. Results: Participants with visual hallucinations had worse cognition and motor function than those without visual hallucinations. In those with visual hallucinations, reduced functional connectivity within the ventral attention network and from the visual to default mode network was found. Connectivity strength between the visual and default mode network correlated with the number of correct responses on a pareidolia task, and connectivity within the ventral attention network with visuospatial performance. Conclusions: Our results add to evidence of dysfunctional connectivity in the visual and attentional networks in those with LBD and visual hallucinations. [ABSTRACT FROM AUTHOR]

Published
2024
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28. Mild cognitive impairment with Lewy bodies: blood perfusion with arterial spin labelling

Author

Firbank, Michael J., O’Brien, John T., Durcan, Rory, Allan, Louise M., Barker, Sally, Ciafone, Joanna, Donaghy, Paul C., Hamilton, Calum A., Lawley, Sarah, Lloyd, Jim, Roberts, Gemma, Taylor, John-Paul, Thomas, Alan J., Firbank, Michael J [0000-0002-9536-0185], Apollo - University of Cambridge Repository, and Firbank, Michael J. [0000-0002-9536-0185]

Subjects
Original Communication, Mild cognitive impairment, Brain, Lewy body disease, Perfusion imaging, behavioral disciplines and activities, Arterial spin labelling, Perfusion, Magnetic resonance imaging, Alzheimer Disease, mental disorders, Humans, Cognitive Dysfunction, Lewy Bodies, Spin Labels, human activities
Abstract

Funder: GE Healthcare; doi: http://dx.doi.org/10.13039/100006775, Funder: NIHR Newcastle Biomedical Research Centre; doi: http://dx.doi.org/10.13039/501100012295, Funder: Newcastle University, Objective: To use arterial spin labelling to investigate differences in perfusion in mild cognitive impairment with Lewy bodies (MCI-LB) compared to Alzheimer type MCI (MCI-AD) and healthy controls. Methods: We obtained perfusion images on 32 MCI-LB, 30 MCI-AD and 28 healthy subjects of similar age. Perfusion relative to cerebellum was calculated, and we aimed to examine differences in relative perfusion between MCI-LB and the other groups. This included whole brain voxelwise comparisons, as well as using predefined region-of-interest ratios of medial occipital to medial temporal, and posterior cingulate to precuneus. Differences in occipital perfusion in eyes open vs eyes closed conditions were also examined. Results: Compared to controls, the MCI-LB showed reduced perfusion in the precuneus, parietal, occipital and fusiform gyrus regions. In our predefined regions, the ratio of perfusion in occipital/medial temporal was significantly lower, and the posterior cingulate/precuneus ratio was significantly higher in MCI-LB compared to controls. Overall, the occipital perfusion was greater in the eyes open vs closed condition, but this did not differ between groups. Conclusion: We found patterns of altered perfusion in MCI-LB which are similar to those seen in dementia with Lewy bodies, with reduction in posterior parietal and occipital regions, but relatively preserved posterior cingulate.

Published
2020
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29. Utility of the pareidolia test in mild cognitive impairment with Lewy bodies and Alzheimer's disease

Author

Hamilton, Calum A, Matthews, Fiona E, Allan, Louise M, Barker, Sally, Ciafone, Joanna, Donaghy, Paul C, Durcan, Rory, Firbank, Michael J, Lawley, Sarah, O'Brien, John T, Roberts, Gemma, Taylor, John-Paul, Thomas, Alan J, Hamilton, Calum A [0000-0002-9812-3150], Matthews, Fiona E [0000-0002-1728-2388], Allan, Louise M [0000-0002-8912-4901], Ciafone, Joanna [0000-0003-4339-2510], Donaghy, Paul C [0000-0001-7195-4846], Durcan, Rory [0000-0002-8897-8737], Firbank, Michael J [0000-0002-9536-0185], O'Brien, John T [0000-0002-0837-5080], Roberts, Gemma [0000-0002-6445-4023], Taylor, John‐Paul [0000-0001-7958-6558], Thomas, Alan J [0000-0002-6667-9533], Apollo - University of Cambridge Repository, and Taylor, John-Paul [0000-0001-7958-6558]

Subjects
Lewy Body Disease, visual hallucinations, behavioral disciplines and activities, nervous system diseases, RESEARCH ARTICLES, RESEARCH ARTICLE, mild cognitive impairment, Alzheimer Disease, pareidolia, mental disorders, Humans, Cognitive Dysfunction, Lewy Bodies, Longitudinal Studies, dementia with Lewy bodies, human activities
Abstract

Funder: NIHR Newcastle Biomedical Research Centre, Funder: Alzheimer's Research UK, Funder: GE Healthcare; Id: http://dx.doi.org/10.13039/100006775, Objectives: Previous research has identified that dementia with Lewy bodies (DLB) has abnormal pareidolic responses which are associated with severity of visual hallucinations (VH), and the pareidolia test accurately classifies DLB with VH. We aimed to assess whether these findings would also be evident at the earlier stage of mild cognitive impairment (MCI) with Lewy bodies (MCI‐LB) in comparison to MCI due to AD (MCI‐AD) and cognitively healthy comparators. Methods: One‐hundred and thirty‐seven subjects were assessed prospectively in a longitudinal study with a mean follow‐up of 1.2 years (max = 3.7): 63 MCI‐LB (22% with VH) and 40 MCI‐AD according to current research diagnostic criteria, and 34 healthy comparators. The pareidolia test was administered annually as a repeated measure. Results: Probable MCI‐LB had an estimated pareidolia rate 1.2–6.7 times higher than MCI‐AD. Pareidolia rates were not associated with concurrent VH, but had a weak association with total score on the North East Visual Hallucinations Inventory. The pareidolia test was not an accurate classifier of either MCI‐LB (Area under curve (AUC) = 0.61), or VH (AUC = 0.56). There was poor sensitivity when differentiating MCI‐LB from controls (41%) or MCI‐AD (27%), though specificity was better (91% and 89%, respectively). Conclusions: Whilst pareidolic responses are specifically more frequent in MCI‐LB than MCI‐AD, sensitivity of the pareidolia test is poorer than in DLB, with fewer patients manifesting VH at the earlier MCI stage. However, the high specificity and ease of use may make it useful in specialist clinics where imaging biomarkers are not available.

Published
2021
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36. Gait‐Related Metabolic Covariance Networks at Rest in Parkinson's Disease

Author

Sigurdsson, Hilmar P., primary, Yarnall, Alison J., additional, Galna, Brook, additional, Lord, Sue, additional, Alcock, Lisa, additional, Lawson, Rachael A., additional, Colloby, Sean J., additional, Firbank, Michael J., additional, Taylor, John‐Paul, additional, Pavese, Nicola, additional, Brooks, David J., additional, O'Brien, John T., additional, Burn, David J., additional, and Rochester, Lynn, additional

Published
2022
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47. Neuropsychological Impairments and Their Cognitive Architecture in Mild Cognitive Impairment (MCI) with Lewy Bodies and MCI-Alzheimer’s Disease

Author

Ciafone, Joanna, primary, Thomas, Alan, additional, Durcan, Rory, additional, Donaghy, Paul C, additional, Hamilton, Calum A, additional, Lawley, Sarah, additional, Roberts, Gemma, additional, Colloby, Sean, additional, Firbank, Michael J, additional, Allan, Louise, additional, Petrides, George, additional, Taylor, John-Paul, additional, O’Brien, John T, additional, and Gallagher, Peter, additional

Published
2021
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49. Neuropsychological Impairments and Their Cognitive Architecture in Mild Cognitive Impairment (MCI) with Lewy Bodies and MCI-Alzheimer's Disease.

Author

Ciafone, Joanna, Thomas, Alan, Durcan, Rory, Donaghy, Paul C, Hamilton, Calum A, Lawley, Sarah, Roberts, Gemma, Colloby, Sean, Firbank, Michael J, Allan, Louise, Petrides, George, Taylor, John-Paul, O'Brien, John T, and Gallagher, Peter

Subjects
VERBAL memory, MILD cognitive impairment, TRAIL Making Test, LEWY body dementia, EXECUTIVE function, VERBAL learning, AUDITORY learning
Abstract

Objective: The present study aimed to clarify the neuropsychological profile of the emergent diagnostic category of Mild Cognitive Impairment with Lewy bodies (MCI-LB) and determine whether domain-specific impairments such as in memory were related to deficits in domain-general cognitive processes (executive function or processing speed). Method: Patients (n = 83) and healthy age- and sex-matched controls (n = 34) underwent clinical and imaging assessments. Probable MCI-LB (n = 44) and MCI-Alzheimer's disease (AD) (n = 39) were diagnosed following National Institute on Aging-Alzheimer's Association (NIA-AA) and dementia with Lewy bodies (DLB) consortium criteria. Neuropsychological measures included cognitive and psychomotor speed, executive function, working memory, and verbal and visuospatial recall. Results: MCI-LB scored significantly lower than MCI-AD on processing speed [Trail Making Test B: p =.03, g =.45; Digit Symbol Substitution Test (DSST): p =.04, g =.47; DSST Error Check: p <.001, g =.68] and executive function [Trail Making Test Ratio (A/B): p =.04, g =.52] tasks. MCI-AD performed worse than MCI-LB on memory tasks, specifically visuospatial (Modified Taylor Complex Figure: p =.01, g =.46) and verbal (Rey Auditory Verbal Learning Test: p =.04, g =.42) delayed recall measures. Stepwise discriminant analysis correctly classified the subtype in 65.1% of MCI patients (72.7% specificity, 56.4% sensitivity). Processing speed accounted for more group-associated variance in visuospatial and verbal memory in both MCI subtypes than executive function, while no significant relationships between measures were observed in controls (all ps >.05) Conclusions: MCI-LB was characterized by executive dysfunction and slowed processing speed but did not show the visuospatial dysfunction expected, while MCI-AD displayed an amnestic profile. However, there was considerable neuropsychological profile overlap and processing speed mediated performance in both MCI subtypes. [ABSTRACT FROM AUTHOR]

Published
2022
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50. Neuroanatomical and cognitive correlates of visual hallucinations in Parkinson’s disease and dementia with Lewy bodies: Voxel-based morphometry and neuropsychological meta-analysis

Author

Pezzoli, Stefania, primary, Sánchez-Valle, Raquel, additional, Solanes, Aleix, additional, Kempton, Matthew J., additional, Bandmann, Oliver, additional, Shin, Jae Il, additional, Cagnin, Annachiara, additional, Goldman, Jennifer G., additional, Merkitch, Doug, additional, Firbank, Michael J., additional, Taylor, John-Paul, additional, Pagonabarraga, Javier, additional, Kulisevsky, Jaime, additional, Blanc, Frederic, additional, Verdolini, Norma, additional, Venneri, Annalena, additional, and Radua, Joaquim, additional

Published
2021
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