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Article ; Online: Quantifying test-retest reliability of repeated objective attentional measures in Lewy body dementia.

Elder, Greg J / Colloby, Sean J / Firbank, Michael J / Taylor, John-Paul

2022 Volume 269, Issue 7, Page(s) 3605–3613

Abstract: Objective cognitive impairment is a feature of Lewy body dementia (LBD), and computerised attentional tasks are commonly used as outcome measures in interventional trials. However, the reliability of these measures, in the absence of interventions, are ... ...

Abstract	Objective cognitive impairment is a feature of Lewy body dementia (LBD), and computerised attentional tasks are commonly used as outcome measures in interventional trials. However, the reliability of these measures, in the absence of interventions, are unknown. This study examined the reliability of these attentional measures at short-term and longer-term follow-up stages. LBD patients (n = 36) completed computerised attentional tasks [simple and choice reaction time, and digit vigilance (SRT, CRT, DV)] at short-term (Day 0-Day 5) and longer-term (4 and 12 weeks) follow-up. Intra-class correlations (ICCs) were calculated to assess test-retest reliability. At short-term, the reciprocal SRT, CRT and DV mean reaction time to correct answers, the reciprocal DV coefficient of variation, and reciprocal power of attention (PoA) all showed excellent levels of reliability (all ICCs > 0.90). The reciprocal PoA showed the highest level of reliability (ICC = 0.978). At longer-term follow-up, only the reciprocal PoA had excellent levels of reliability (ICC = 0.927). Reciprocal SRT, CRT and DV reaction time to correct answers, and the CRT coefficient of variation values, showed good levels of test-retest reliability (ICCs ≥ 0.85). Contrary to expectations, most attentional measures demonstrated high levels of test-retest reliability at both short-term and longer-term follow-up time points. The reciprocal PoA composite measure demonstrated excellent levels of test-retest reliability, both in the short-term and long-term. This indicates that objective attentional tasks are suitable outcome measures in LBD studies and that the composite PoA measure may offer the highest levels of reliability.
MeSH term(s)	Attention ; Humans ; Lewy Body Disease/diagnosis ; Lewy Body Disease/psychology ; Reaction Time ; Reproducibility of Results
Language	English
Publishing date	2022-01-27
Publishing country	Germany
Document type	Journal Article
ZDB-ID	187050-6
ISSN	1432-1459 ; 0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
ISSN (online)	1432-1459
ISSN	0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
DOI	10.1007/s00415-022-10977-4
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Article: Imaging in Dementia With Lewy Bodies: An Overview.

Watson, Rosie / Colloby, Sean J

Journal of geriatric psychiatry and neurology

2016 Volume 29, Issue 5, Page(s) 254–260

Abstract: Dementia with Lewy bodies (DLB) while common in older age can present a diagnostic challenge to clinicians and is often misdiagnosed as Alzheimer disease (AD). Imaging studies have improved our understanding of the neurobiological changes in DLB during ... ...

Abstract	Dementia with Lewy bodies (DLB) while common in older age can present a diagnostic challenge to clinicians and is often misdiagnosed as Alzheimer disease (AD). Imaging studies have improved our understanding of the neurobiological changes in DLB during life and how they differ from AD. This has led to significant advances in the development of new techniques, such as dopaminergic imaging, which can aid the clinical diagnosis. Other functional imaging methods also show promise in helping to assess the influence of differing pathologies in DLB, most notably, AD-related and vascular pathology during life. This article will provide an overview of the main imaging findings in DLB.
MeSH term(s)	Aged ; Alzheimer Disease/diagnostic imaging ; Alzheimer Disease/pathology ; Atrophy/diagnostic imaging ; Atrophy/etiology ; Atrophy/pathology ; Brain/diagnostic imaging ; Brain/pathology ; Brain Mapping ; Dementia/diagnostic imaging ; Dementia/pathology ; Humans ; Lewy Bodies/pathology ; Lewy Body Disease/diagnostic imaging ; Lewy Body Disease/pathology ; Magnetic Resonance Imaging/methods ; Tomography, Emission-Computed, Single-Photon ; Tomography, X-Ray Computed
Language	English
Publishing date	2016-09
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1035760-9
ISSN	0891-9887
ISSN	0891-9887
DOI	10.1177/0891988716654984
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Article ; Online: Transcranial Direct Current Stimulation in the Treatment of Visual Hallucinations in Charles Bonnet Syndrome: A Randomized Placebo-Controlled Crossover Trial.

daSilva Morgan, Katrina / Schumacher, Julia / Collerton, Daniel / Colloby, Sean / Elder, Greg J / Olsen, Kirsty / Ffytche, Dominic H / Taylor, John-Paul

Ophthalmology

2022 Volume 129, Issue 12, Page(s) 1368–1379

Abstract: Objective: To investigate the potential therapeutic benefits and tolerability of inhibitory transcranial direct current stimulation (tDCS) on the remediation of visual hallucinations in Charles Bonnet syndrome (CBS).: Design: Randomized, double- ... ...

Abstract	Objective: To investigate the potential therapeutic benefits and tolerability of inhibitory transcranial direct current stimulation (tDCS) on the remediation of visual hallucinations in Charles Bonnet syndrome (CBS). Design: Randomized, double-masked, placebo-controlled crossover trial. Participants: Sixteen individuals diagnosed with CBS secondary to visual impairment caused by eye disease experiencing recurrent visual hallucinations. Intervention: All participants received 4 consecutive days of active and placebo cathodal stimulation (current density: 0.29 mA/cm Main outcome measures: Ratings of visual hallucination frequency and duration following active and placebo stimulation, accounting for treatment order, using a 2 × 2 repeated-measures model. Secondary outcomes included impact ratings of visual hallucinations and electrophysiological measures. Results: When compared with placebo treatment, active inhibitory stimulation of visual cortex resulted in a significant reduction in the frequency of visual hallucinations measured by the North East Visual Hallucinations Interview, with a moderate-to-large effect size. Impact measures of visual hallucinations improved in both placebo and active conditions, suggesting support and education for CBS may have therapeutic benefits. Participants who demonstrated greater occipital excitability on electroencephalography assessment at the start of treatment were more likely to report a positive treatment response. Stimulation was found to be tolerable in all participants, with no significant adverse effects reported, including no deterioration in preexisting visual impairment. Conclusions: Findings indicate that inhibitory tDCS of visual cortex may reduce the frequency of visual hallucinations in people with CBS, particularly individuals who demonstrate greater occipital excitability prior to stimulation. tDCS may offer a feasible intervention option for CBS with no significant side effects, warranting larger-scale clinical trials to further characterize its efficacy.
MeSH term(s)	Humans ; Charles Bonnet Syndrome/complications ; Charles Bonnet Syndrome/therapy ; Transcranial Direct Current Stimulation/adverse effects ; Transcranial Direct Current Stimulation/methods ; Cross-Over Studies ; Hallucinations/therapy ; Hallucinations/diagnosis ; Hallucinations/etiology ; Vision, Low/etiology
Language	English
Publishing date	2022-07-09
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	392083-5
ISSN	1549-4713 ; 0161-6420
ISSN (online)	1549-4713
ISSN	0161-6420
DOI	10.1016/j.ophtha.2022.06.041
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Article ; Online: Spatial covariance analysis of FDG-PET and HMPAO-SPECT for the differential diagnosis of dementia with Lewy bodies and Alzheimer's disease.

Ingram, Matthew / Colloby, Sean J / Firbank, Michael J / Lloyd, Jim J / O'Brien, John T / Taylor, John-Paul

Psychiatry research. Neuroimaging

2022 Volume 322, Page(s) 111460

Abstract: We investigated diagnostic characteristics of spatial covariance analysis (SCA) of FDG-PET and HMPAO-SPECT scans in the differential diagnosis of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), in comparison with visual ratings and region ... ...

Abstract	We investigated diagnostic characteristics of spatial covariance analysis (SCA) of FDG-PET and HMPAO-SPECT scans in the differential diagnosis of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), in comparison with visual ratings and region of interest (ROI) analysis. Sixty-seven patients (DLB 29, AD 38) had both HMPAO-SPECT and FDG-PET scans. Spatial covariance patterns were used to separate AD and DLB in an initial derivation group (DLB n=15, AD n=19), before being forward applied to an independent group (DLB n=14, AD n=19). Visual ratings were by consensus, with ROI analysis utilising medial occipital/medial temporal uptake ratios. SCA of HMPAO-SPECT performed poorly (AUC 0.59±0.10), whilst SCA of FDG-PET (AUC 0.83±0.07) was significantly better. For FDG-PET, SCA showed similar diagnostic performance to ROI analysis (AUC 0.84±0.08) and visual rating (AUC 0.82±0.08). In contrast to ROI analysis, there was little concordance between SCA and visual ratings of FDG-PET scans. We conclude that SCA of FDG-PET outperforms that of HMPAO-SPECT. SCA of FDG-PET also performed similarly to the other analytical approaches, despite the limitations of a relatively small SCA derivation group. Compared to visual rating, SCA of FDG-PET relies on different sources of group variance to separate DLB from AD.
MeSH term(s)	Alzheimer Disease/diagnostic imaging ; Diagnosis, Differential ; Fluorodeoxyglucose F18 ; Humans ; Lewy Body Disease/diagnostic imaging ; Positron-Emission Tomography/methods ; Tomography, Emission-Computed, Single-Photon/methods
Chemical Substances	Fluorodeoxyglucose F18 (0Z5B2CJX4D)
Language	English
Publishing date	2022-02-15
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	445361-x
ISSN	1872-7506 ; 1872-7123 ; 0925-4927 ; 0165-1781
ISSN (online)	1872-7506 ; 1872-7123
ISSN	0925-4927 ; 0165-1781
DOI	10.1016/j.pscychresns.2022.111460
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Article ; Online: Identifying parkinsonism in mild cognitive impairment.

Fernando, Rishira / Thomas, Alan J / Hamilton, Calum A / Durcan, Rory / Barker, Sally / Ciafone, Joanna / Barnett, Nicola / Olsen, Kirsty / Firbank, Michael / Roberts, Gemma / Lloyd, Jim / Petrides, George / Colloby, Sean / Allan, Louise M / McKeith, Ian G / O'Brien, John T / Taylor, John-Paul / Donaghy, Paul C

Journal of the neurological sciences

2024 Volume 458, Page(s) 122941

Abstract: Introduction: Clinical parkinsonism is a core diagnostic feature for mild cognitive impairment with Lewy bodies (MCI-LB) but can be challenging to identify. A five-item scale derived from the Unified Parkinson's Disease Rating Scale (UPDRS) has been ... ...

Abstract	Introduction: Clinical parkinsonism is a core diagnostic feature for mild cognitive impairment with Lewy bodies (MCI-LB) but can be challenging to identify. A five-item scale derived from the Unified Parkinson's Disease Rating Scale (UPDRS) has been recommended for the assessment of parkinsonism in dementia. This study aimed to determine whether the five-item scale is effective to identify parkinsonism in MCI. Methods: Participants with MCI from two cohorts (n = 146) had a physical examination including the UPDRS and [123I]-FP-CIT SPECT striatal dopaminergic imaging. Participants were classified as having clinical parkinsonism (P+) or no parkinsonism (P-), and with abnormal striatal dopaminergic imaging (D+) or normal imaging (D-). The five-item scale was the sum of UPDRS tremor at rest, bradykinesia, action tremor, facial expression, and rigidity scores. The ability of the scale to differentiate P+D+ and P-D- participants was examined. Results: The five-item scale had an AUROC of 0.92 in Cohort 1, but the 7/8 cut-off defined for dementia had low sensitivity to identify P+D+ participants (sensitivity 25%, specificity 100%). Optimal sensitivity and specificity was obtained at a 3/4 cut-off (sensitivity 83%, specificity 88%). In Cohort 2, the five-item scale had an AUROC of 0.97, and the 3/4 cut-off derived from Cohort 1 showed sensitivity of 100% and a specificity of 82% to differentiate P+D+ from P-D- participants. The five-item scale was not effective in differentiating D+ from D- participants. Conclusions: The five-item scale is effective to identify parkinsonism in MCI, but a lower threshold must be used in MCI compared with dementia.
MeSH term(s)	Humans ; Lewy Body Disease/diagnosis ; Lewy Body Disease/diagnostic imaging ; Parkinsonian Disorders ; Cognitive Dysfunction/diagnostic imaging ; Cognitive Dysfunction/metabolism ; Tomography, Emission-Computed, Single-Photon ; Alzheimer Disease/metabolism
Language	English
Publishing date	2024-02-15
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	80160-4
ISSN	1878-5883 ; 0022-510X ; 0374-8642
ISSN (online)	1878-5883
ISSN	0022-510X ; 0374-8642
DOI	10.1016/j.jns.2024.122941
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Article ; Online: Consecutive sessions of transcranial direct current stimulation do not remediate visual hallucinations in Lewy body dementia: a randomised controlled trial.

Elder, Greg J / Colloby, Sean J / Firbank, Michael J / McKeith, Ian G / Taylor, John-Paul

Alzheimer's research & therapy

2019 Volume 11, Issue 1, Page(s) 9

Abstract: Background: Complex visual hallucinations are common in Lewy body dementia (LBD) and can cause significant patient and caregiver distress. Current treatments are primarily pharmacological in nature and have limited efficacy and associated side effects. ... ...

Abstract	Background: Complex visual hallucinations are common in Lewy body dementia (LBD) and can cause significant patient and caregiver distress. Current treatments are primarily pharmacological in nature and have limited efficacy and associated side effects. The objective of this study was to assess the effects of consecutive sessions of transcranial direct current stimulation (tDCS) on visual hallucination frequency and severity in LBD, at short-term and long-term follow-up stages. Methods: The study was a randomised, double-blind, placebo-controlled trial involving 40 participants with LBD (M Results: Complete study data were obtained from 36 participants. There was an overall improvement in visual hallucinations (NPI) for both groups at day 5 relative to baseline, with a medium-to-large effect size; however, compared to placebo, active tDCS did not result in any improvements in visual hallucinations (NPI) at day 5 relative to baseline, or at month 1 or month 3 follow-up time points. Additionally, comparisons of secondary outcome measures showed that active tDCS did not result in any improvements on any measure (visual cortical excitability, attentional and visuoperceptual tasks or cognitive measures) at any time point. Conclusions: Repeated consecutive sessions of parietal anodal tDCS, and occipital cathodal tDCS, do not improve visual hallucinations or visuoperceptual function, or alter visual cortical excitability in LBD. Trial registration: ISRCTN, ISRCTN40214749 . Registered on 25 October 2013.
MeSH term(s)	Aged ; Aged, 80 and over ; Double-Blind Method ; Female ; Follow-Up Studies ; Hallucinations/diagnosis ; Hallucinations/psychology ; Hallucinations/therapy ; Humans ; Lewy Body Disease/diagnosis ; Lewy Body Disease/psychology ; Lewy Body Disease/therapy ; Male ; Photic Stimulation/methods ; Prospective Studies ; Reaction Time/physiology ; Transcranial Direct Current Stimulation/methods ; Transcranial Direct Current Stimulation/trends
Language	English
Publishing date	2019-01-18
Publishing country	England
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	2506521-X
ISSN	1758-9193 ; 1758-9193
ISSN (online)	1758-9193
ISSN	1758-9193
DOI	10.1186/s13195-018-0465-9
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Article ; Online: Neuropathological Changes in Dementia With Lewy Bodies and the Cingulate Island Sign.

Patterson, Lina / Firbank, Michael J / Colloby, Sean J / Attems, Johannes / Thomas, Alan J / Morris, Christopher M

Journal of neuropathology and experimental neurology

2019 Volume 78, Issue 8, Page(s) 717–724

Abstract: The cingulate island sign (CIS) refers to the relative sparing of metabolism in the posterior cingulate cortex (PCC) and represents an important biomarker in distinguishing dementia with Lewy bodies (DLB) from Alzheimer disease (AD). The underlying basis ...

Abstract	The cingulate island sign (CIS) refers to the relative sparing of metabolism in the posterior cingulate cortex (PCC) and represents an important biomarker in distinguishing dementia with Lewy bodies (DLB) from Alzheimer disease (AD). The underlying basis of the CIS is unknown; therefore, our aim was to investigate which neurodegenerative changes underpin the formation of CIS. Using quantitative neuropathology, α-synuclein, phosphorylated Tau, and amyloid-β pathology was assessed in 12 DLB, 9 AD and 6 age-matched control patients in the anterior cingulate (ACC), midcingulate, PCC, precuneus/cuneus and parahippocampal gyrus. All participants had undergone 99mTc-hexamethylpropyleneamine oxime (HMPAO) single-photon emission computed tomography imaging during life to define the presence or absence of CIS. In the DLB group, no significant correlations were observed between CIS ratios and neurodegenerative pathology in PCC. In DLB, however, the ACC showed lower HMPAO uptake, as well as significantly higher α-synuclein and amyloid-β burden compared with PCC, possibly underlying the relative preservation of perfusion in PCC when compared with ACC. Our findings suggest that neurodegenerative pathology does not directly correlate with the CIS in DLB, and other metabolic or pathological changes are therefore more likely to be relevant for the development of the CIS.
Language	English
Publishing date	2019-07-02
Publishing country	England
Document type	Journal Article
ZDB-ID	3088-0
ISSN	1554-6578 ; 0022-3069
ISSN (online)	1554-6578
ISSN	0022-3069
DOI	10.1093/jnen/nlz047
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Article ; Online: Cortical thinning in dementia with Lewy bodies and Parkinson disease dementia.

Colloby, Sean J / Watson, Rosie / Blamire, Andrew M / O'Brien, John T / Taylor, John-Paul

The Australian and New Zealand journal of psychiatry

2019 Volume 54, Issue 6, Page(s) 633–643

Abstract: Background: We investigated the structural changes associated with Alzheimer's disease, dementia with Lewy bodies and Parkinson disease dementia by means of cortical thickness analysis.: Methods: Two hundred and forty-five participants: 76 Alzheimer' ... ...

Abstract	Background: We investigated the structural changes associated with Alzheimer's disease, dementia with Lewy bodies and Parkinson disease dementia by means of cortical thickness analysis. Methods: Two hundred and forty-five participants: 76 Alzheimer's disease, 65 dementia with Lewy bodies, 29 Parkinson disease dementia and 76 cognitively normal controls underwent 3-T T1-weighted magnetic resonance imaging and clinical and cognitive assessments. We implemented FreeSurfer to obtain cortical thickness estimates to contrast patterns of cortical thinning across groups and their clinical correlates. Results: In Alzheimer's disease and dementia with Lewy bodies, a largely similar pattern of regional cortical thinning was observed relative to controls apart from a more severe loss within the entorhinal and parahippocampal structures in Alzheimer's disease. In Parkinson disease dementia, regional cortical thickness was indistinguishable from controls and dementia with Lewy bodies, suggesting an 'intermediate' pattern of regional cortical change. In terms of global cortical thickness, group profiles were controls > Parkinson disease dementia > dementia with Lewy bodies > Alzheimer's disease (F Conclusion: In a large and well-characterised cohort of people with dementia, regional cortical thinning in dementia with Lewy bodies was broadly similar to Alzheimer's disease. There was preservation of the medial temporal lobe structures in dementia with Lewy bodies compared with Alzheimer's disease, supporting its inclusion as a supportive biomarker in the revised clinical criteria for dementia with Lewy bodies. However, there was less global cortical thinning in Parkinson disease dementia, with no significant regional difference between Parkinson disease dementia and controls. These findings highlight the overlap across the Alzheimer's disease/Parkinson disease dementia spectrum and the potential for differing mechanisms underlying neurodegeneration and cognition in dementia with Lewy bodies and Parkinson disease dementia.
Language	English
Publishing date	2019-11-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	221140-3
ISSN	1440-1614 ; 0004-8674
ISSN (online)	1440-1614
ISSN	0004-8674
DOI	10.1177/0004867419885165
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Article ; Online: Serial Nigrostriatal Dopaminergic Imaging in Mild Cognitive Impairment With Lewy Bodies, Alzheimer Disease, and Age-Matched Controls.

Durcan, Rory / Roberts, Gemma / Hamilton, Calum A / Donaghy, Paul C / Howe, Kim / Colloby, Sean J / Allan, Louise M / Firbank, Michael / Lawley, Sarah / Petrides, George S / Lloyd, Jim J / Taylor, John-Paul / O'Brien, John T / Thomas, Alan J

Neurology

2023 Volume 101, Issue 12, Page(s) e1196–e1205

Abstract: Background and objectives: Progressive nigrostriatal pathway degeneration occurs in individuals with dementia with Lewy bodies (LB). Our objective was to investigate whether repeat 123[I]-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane ...

Abstract	Background and objectives: Progressive nigrostriatal pathway degeneration occurs in individuals with dementia with Lewy bodies (LB). Our objective was to investigate whether repeat 123[I]-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane (FP-CIT) single photon emission computed tomography (SPECT) can identify progressive dopaminergic loss in mild cognitive impairment (MCI) with Lewy bodies (MCI-LB). Methods: Individuals with MCI-LB and MCI due to Alzheimer disease (MCI-AD) underwent comprehensive clinical assessment, 123[I]-FP-CIT SPECT at baseline and annual reviews, and baseline cardiac Results: We recruited 20 individuals with MCI-AD, 11 with possible MCI-LB, 25 with probable MCI-LB, and 29 age-matched controls. The mean time between baseline and the final image was 1.6 years (SD = 0.9, range 1.0-4.3). The annual estimated change in SBR was 0.23 for controls (95% CI -0.07 to 0.53), -0.09 (-0.55 to 0.36) for MCI-AD, -0.50 (-1.03 to 0.04) for possible MCI-LB, and -0.48 (-0.89 to -0.06) for probable MCI-LB. The median annual percentage change in SBR in MCI-LB was -5.6% (95% CI -8.2% to -2.9%) and 2.1% (-3.5% to 8.0%) for MCI-AD. The extrapolated time for a normal scan to become abnormal was 6 years. Controls and MCI-AD showed no significant change in dopaminergic binding over time. The mean test-retest variation in controls was 12% (SD 5.5%), which cautions against overinterpretation of small changes on repeat scanning. Discussion: Progressive dopaminergic loss in the striatum is detectable using 123[I]-FP-CIT SPECT in MCI-LB at a group level. In clinical practice, individual change in striatal 123[I]-FP-CIT uptake seems to be of limited diagnostic value because of high test-retest variation. Classification of evidence: This study provides Class II evidence that longitudinal declines in striatal uptake measured using 123[I]-FP-CIT SPECT are associated with MCI due to Lewy body disease but not MCI due to Alzheimer disease.
MeSH term(s)	Humans ; Aged ; Alzheimer Disease/metabolism ; Dopaminergic Imaging ; Tropanes/metabolism ; Lewy Body Disease/complications ; Tomography, Emission-Computed, Single-Photon/methods ; Cognitive Dysfunction/metabolism
Chemical Substances	2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane (155797-99-2) ; Tropanes
Language	English
Publishing date	2023-07-31
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0000000000207621
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Article ; Online: Functional and structural brain network correlates of visual hallucinations in Lewy body dementia.

Mehraram, Ramtin / Peraza, Luis R / Murphy, Nicholas R E / Cromarty, Ruth A / Graziadio, Sara / O'Brien, John T / Killen, Alison / Colloby, Sean J / Firbank, Michael / Su, Li / Collerton, Daniel / Taylor, John Paul / Kaiser, Marcus

Brain : a journal of neurology

2022 Volume 145, Issue 6, Page(s) 2190–2205

Abstract: Visual hallucinations are a common feature of Lewy body dementia. Previous studies have shown that visual hallucinations are highly specific in differentiating Lewy body dementia from Alzheimer's disease dementia and Alzheimer-Lewy body mixed pathology ... ...

Abstract	Visual hallucinations are a common feature of Lewy body dementia. Previous studies have shown that visual hallucinations are highly specific in differentiating Lewy body dementia from Alzheimer's disease dementia and Alzheimer-Lewy body mixed pathology cases. Computational models propose that impairment of visual and attentional networks is aetiologically key to the manifestation of visual hallucinations symptomatology. However, there is still a lack of experimental evidence on functional and structural brain network abnormalities associated with visual hallucinations in Lewy body dementia. We used EEG source localization and network based statistics to assess differential topographical patterns in Lewy body dementia between 25 participants with visual hallucinations and 17 participants without hallucinations. Diffusion tensor imaging was used to assess structural connectivity between thalamus, basal forebrain and cortical regions belonging to the functionally affected network component in the hallucinating group, as assessed with network based statistics. The number of white matter streamlines within the cortex and between subcortical and cortical regions was compared between hallucinating and not hallucinating groups and correlated with average EEG source connectivity of the affected subnetwork. Moreover, modular organization of the EEG source network was obtained, compared between groups and tested for correlation with structural connectivity. Network analysis showed that compared to non-hallucinating patients, those with hallucinations feature consistent weakened connectivity within the visual ventral network, and between this network and default mode and ventral attentional networks, but not between or within attentional networks. The occipital lobe was the most functionally disconnected region. Structural analysis yielded significantly affected white matter streamlines connecting the cortical regions to the nucleus basalis of Meynert and the thalamus in hallucinating compared to not hallucinating patients. The number of streamlines in the tract between the basal forebrain and the cortex correlated with cortical functional connectivity in non-hallucinating patients, while a correlation emerged for the white matter streamlines connecting the functionally affected cortical regions in the hallucinating group. This study proposes, for the first time, differential functional networks between hallucinating and not hallucinating Lewy body dementia patients, and provides empirical evidence for existing models of visual hallucinations. Specifically, the outcome of the present study shows that the hallucinating condition is associated with functional network segregation in Lewy body dementia and supports the involvement of the cholinergic system as proposed in the current literature.
MeSH term(s)	Alzheimer Disease/pathology ; Brain/pathology ; Diffusion Tensor Imaging ; Hallucinations/etiology ; Humans ; Lewy Body Disease/complications ; Lewy Body Disease/diagnostic imaging ; Lewy Body Disease/pathology
Language	English
Publishing date	2022-03-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	80072-7
ISSN	1460-2156 ; 0006-8950
ISSN (online)	1460-2156
ISSN	0006-8950
DOI	10.1093/brain/awac094
Database	MEDical Literature Analysis and Retrieval System OnLINE

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