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Article ; Online: Author response: Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium.

McKeith, Ian G

2018 Volume 90, Issue 6, Page(s) 300–301

MeSH term(s)	Consensus ; Dementia ; Humans ; Lewy Bodies ; Lewy Body Disease
Language	English
Publishing date	2018-01-31
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0000000000004919
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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: The challenges of COVID-19 for people with dementia with Lewy bodies and family caregivers.

Killen, Alison / Olsen, Kirsty / McKeith, Ian G / Thomas, Alan J / O'Brien, John T / Donaghy, Paul / Taylor, John-Paul

International journal of geriatric psychiatry

2020 Volume 35, Issue 12, Page(s) 1431–1436

Keywords	covid19
Language	English
Publishing date	2020-08-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	806736-3
ISSN	1099-1166 ; 0885-6230
ISSN (online)	1099-1166
ISSN	0885-6230
DOI	10.1002/gps.5393
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Article ; Online: Cholinergic muscarinic M

Colloby, Sean J / Nathan, Pradeep J / McKeith, Ian G / Bakker, Geor / O'Brien, John T / Taylor, John-Paul

Brain communications

2020 Volume 2, Issue 2, Page(s) fcaa098

Abstract: Cholinergic dysfunction is central in dementia with Lewy bodies, possibly contributing to the cognitive and psychiatric phenotypes of this condition. We investigated baseline muscarinic ... ...

Abstract	Cholinergic dysfunction is central in dementia with Lewy bodies, possibly contributing to the cognitive and psychiatric phenotypes of this condition. We investigated baseline muscarinic M
Language	English
Publishing date	2020-07-15
Publishing country	England
Document type	Journal Article
ISSN	2632-1297
ISSN (online)	2632-1297
DOI	10.1093/braincomms/fcaa098
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Article ; Online: Defining the Riddle in Order to Solve It: There Is More Than One "Parkinson's Disease".

Outeiro, Tiago F / Alcalay, Roy N / Antonini, Angelo / Attems, Johannes / Bonifati, Vincenzo / Cardoso, Francisco / Chesselet, Marie-Françoise / Hardy, John / Madeo, Graziella / McKeith, Ian / Mollenhauer, Brit / Moore, Darren J / Rascol, Olivier / Schlossmacher, Michael G / Soreq, Hermona / Stefanis, Leonidas / Ferreira, Joaquim J

Movement disorders : official journal of the Movement Disorder Society

2023 Volume 38, Issue 7, Page(s) 1127–1142

Abstract: Background: More than 200 years after James Parkinsondescribed a clinical syndrome based on his astute observations, Parkinson's disease (PD) has evolved into a complex entity, akin to the heterogeneity of other complex human syndromes of the central ... ...

Abstract	Background: More than 200 years after James Parkinsondescribed a clinical syndrome based on his astute observations, Parkinson's disease (PD) has evolved into a complex entity, akin to the heterogeneity of other complex human syndromes of the central nervous system such as dementia, motor neuron disease, multiple sclerosis, and epilepsy. Clinicians, pathologists, and basic science researchers evolved arrange of concepts andcriteria for the clinical, genetic, mechanistic, and neuropathological characterization of what, in their best judgment, constitutes PD. However, these specialists have generated and used criteria that are not necessarily aligned between their different operational definitions, which may hinder progress in solving the riddle of the distinct forms of PD and ultimately how to treat them. Objective: This task force has identified current in consistencies between the definitions of PD and its diverse variants in different domains: clinical criteria, neuropathological classification, genetic subtyping, biomarker signatures, and mechanisms of disease. This initial effort for "defining the riddle" will lay the foundation for future attempts to better define the range of PD and its variants, as has been done and implemented for other heterogeneous neurological syndromes, such as stroke and peripheral neuropathy. We strongly advocate for a more systematic and evidence-based integration of our diverse disciplines by looking at well-defined variants of the syndrome of PD. Conclusion: Accuracy in defining endophenotypes of "typical PD" across these different but interrelated disciplines will enable better definition of variants and their stratification in therapeutic trials, a prerequisite for breakthroughs in the era of precision medicine. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
MeSH term(s)	Humans ; Parkinson Disease/genetics ; Syndrome ; Biomarkers ; Forecasting ; Central Nervous System/pathology
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-05-08
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	607633-6
ISSN	1531-8257 ; 0885-3185
ISSN (online)	1531-8257
ISSN	0885-3185
DOI	10.1002/mds.29419
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Zs.A 2555: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 238: Show issues

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Article ; Online: Clinical symptoms in mild cognitive impairment with Lewy bodies: Frequency, time of onset, and discriminant ability.

Donaghy, Paul C / Hamilton, Calum / Durcan, Rory / Lawley, Sarah / Barker, Sally / Ciafone, Joanna / Barnett, Nicola / Olsen, Kirsty / Firbank, Michael / Roberts, Gemma / Lloyd, Jim / Allan, Louise M / Saha, Ranjan / McKeith, Ian G / O'Brien, John T / Taylor, John-Paul / Thomas, Alan J

European journal of neurology

2023 Volume 30, Issue 6, Page(s) 1585–1593

Abstract: Background and purpose: Mild cognitive impairment with Lewy bodies (MCI-LB) is associated with a range of cognitive, motor, neuropsychiatric, sleep, autonomic, and visual symptoms. We investigated the cumulative frequency of symptoms in a longitudinal ... ...

Abstract	Background and purpose: Mild cognitive impairment with Lewy bodies (MCI-LB) is associated with a range of cognitive, motor, neuropsychiatric, sleep, autonomic, and visual symptoms. We investigated the cumulative frequency of symptoms in a longitudinal cohort of MCI-LB compared with MCI due to Alzheimer disease (MCI-AD) and analysed the ability of a previously described 10-point symptom scale to differentiate MCI-LB and MCI-AD, in an independent cohort. Methods: Participants with probable MCI-LB (n = 70), MCI-AD (n = 51), and controls (n = 34) had a detailed clinical assessment and annual follow-up (mean duration = 1.7 years). The presence of a range of symptoms was ascertained using a modified version of the Lewy Body Disease Association Comprehensive LBD Symptom Checklist at baseline assessment and then annually. Results: MCI-LB participants experienced a greater mean number of symptoms (24.2, SD = 7.6) compared with MCI-AD (11.3, SD = 7.4) and controls (4.2, SD = 3.1; p < 0.001 for all comparisons). A range of cognitive, parkinsonian, neuropsychiatric, sleep, and autonomic symptoms were significantly more common in MCI-LB than MCI-AD, although when present, the time of onset was similar between the two groups. A previously defined 10-point symptom scale demonstrated very good discrimination between MCI-LB and MCI-AD (area under the receiver operating characteristic curve = 0.91, 95% confidence interval = 0.84-0.98), replicating our previous finding in a new cohort. Conclusions: MCI-LB is associated with the frequent presence of a particular profile of symptoms compared to MCI-AD. Clinicians should look for evidence of these symptoms in MCI and be aware of the potential for treatment. The presence of these symptoms may help to discriminate MCI-LB from MCI-AD.
MeSH term(s)	Humans ; Lewy Bodies ; Lewy Body Disease/diagnosis ; Lewy Body Disease/complications ; Alzheimer Disease/complications ; Cognitive Dysfunction/psychology ; ROC Curve
Language	English
Publishing date	2023-03-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1280785-0
ISSN	1468-1331 ; 1351-5101 ; 1471-0552
ISSN (online)	1468-1331
ISSN	1351-5101 ; 1471-0552
DOI	10.1111/ene.15783
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Zs.A 4738: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 592: Show issues

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Article: Correction: Clinical outcome measures in dementia with Lewy bodies trials: critique and recommendations.

Rodriguez-Porcel, Federico / Wyman-Chick, Kathryn A / Abdelnour Ruiz, Carla / Toledo, Jon B / Ferreira, Daniel / Urwyler, Prabitha / Weil, Rimona S / Kane, Joseph / Pilotto, Andrea / Rongve, Arvid / Boeve, Bradley / Taylor, John-Paul / McKeith, Ian / Aarsland, Dag / Lewis, Simon J G

Translational neurodegeneration

2022 Volume 11, Issue 1, Page(s) 29

Language	English
Publishing date	2022-05-17
Publishing country	England
Document type	Published Erratum
ZDB-ID	2653701-1
ISSN	2047-9158
ISSN	2047-9158
DOI	10.1186/s40035-022-00306-0
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Article ; Online: Inflammation in dementia with Lewy bodies.

Amin, Jay / Erskine, Daniel / Donaghy, Paul C / Surendranathan, Ajenthan / Swann, Peter / Kunicki, Amy P / Boche, Delphine / Holmes, Clive / McKeith, Ian G / O'Brien, John T / Teeling, Jessica L / Thomas, Alan J

Neurobiology of disease

2022 Volume 168, Page(s) 105698

Abstract: Dementia with Lewy bodies (DLB) is the second most common neurodegenerative cause of dementia, behind Alzheimer's disease (AD). The profile of inflammation in AD has been extensively researched in recent years, with evidence that chronic peripheral ... ...

Abstract	Dementia with Lewy bodies (DLB) is the second most common neurodegenerative cause of dementia, behind Alzheimer's disease (AD). The profile of inflammation in AD has been extensively researched in recent years, with evidence that chronic peripheral inflammation in midlife increases the risk of late-onset AD, and data supporting inflammation being associated with disease progression. In contrast, our understanding of the role of inflammation in DLB is less developed. Most research to date has examined inflammation in related disorders, such as Parkinson's disease, but there is now a growing range of literature examining inflammation in DLB itself. We present a review of the literature in this field, exploring a range of research methodologies including those quantifying markers of inflammation in cerebrospinal fluid, peripheral blood, post-mortem brain tissue, and using neuroimaging and preclinical data. Our review reveals evidence from PET imaging and peripheral blood analysis to support an increase in cerebral and peripheral inflammation in mild or prodromal DLB, that dissipates with disease progression. We present evidence from post-mortem brain tissue and pre-clinical studies that indicate α-synuclein directly promotes inflammation, but that also support the presence of AD co-pathology as an important factor in the profile of neuroinflammation in DLB. We propose that specific markers of inflammation may play a sentinel role in the mild stage of the disease, particularly when combined with AD pathology. We advocate further examination of the profile of inflammation in DLB through robust longitudinal studies, to enhance our understanding of the pathogenesis of the disease. The goal should be to utilise future results to develop a composite biomarker to aid diagnosis of DLB, and to potentially identify novel therapeutic targets.
MeSH term(s)	Alzheimer Disease/complications ; Biomarkers/cerebrospinal fluid ; Disease Progression ; Humans ; Inflammation ; Lewy Bodies/pathology ; Lewy Body Disease/pathology
Chemical Substances	Biomarkers
Language	English
Publishing date	2022-03-18
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1211786-9
ISSN	1095-953X ; 0969-9961
ISSN (online)	1095-953X
ISSN	0969-9961
DOI	10.1016/j.nbd.2022.105698
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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: Progression of Clinical Features in Lewy Body Dementia Can Be Detected Over 6 Months.

Matar, Elie / White, Simon R / Taylor, John-Paul / Thomas, Alan / McKeith, Ian G / Kane, Joseph P M / Surendranathan, Ajenthan / Halliday, Glenda M / Lewis, Simon J G / O'Brien, John T

Neurology

2021 Volume 97, Issue 10, Page(s) e1031–e1040

Abstract: Objective: This study aimed to quantify the trajectory and magnitude of change of the key clinical features and corresponding symptom domains of dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD), including global cognition, ... ...

Abstract	Objective: This study aimed to quantify the trajectory and magnitude of change of the key clinical features and corresponding symptom domains of dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD), including global cognition, parkinsonism, recurrent visual hallucinations, cognitive fluctuations, and sleep disturbance. Methods: One hundred sixteen patients with Lewy body dementia (DLB = 72, PDD = 44) underwent assessment at baseline and 3 and 6 months as part of a prospective multicenter randomized controlled trial. Linear mixed models were constructed for core outcome measures using the Mini-Mental State Examination (MMSE), motor section of the Unified Parkinson's Disease Rating Scale (UPDRS-III), Dementia Cognitive Fluctuations Scale (DCFS), and Neuropsychiatric Inventory (NPI). Results: Within the time frame of our study (6 months), we were able to identify a significant cognitive decline of 1.3 points on the MMSE ( Discussion: Clinically significant rates of change in core clinical features can be detected and quantified in Lewy body dementia over a relatively short period (6 months) using common clinical instruments and thus may be useful as clinical endpoints for therapeutic trials of disease-modifying and symptomatic agents.
MeSH term(s)	Aged ; Aged, 80 and over ; Cognitive Dysfunction/physiopathology ; Disease Progression ; Female ; Humans ; Lewy Body Disease/physiopathology ; Longitudinal Studies ; Male ; Parkinson Disease/physiopathology
Language	English
Publishing date	2021-08-17
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.0000000000012450
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