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Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium.

ABSTRACT: The Dementia with Lewy Bodies (DLB) Consortium has refined its recommendations about the clinical and pathologic diagnosis of DLB, updating the previous report, which has been in widespread use for the last decade. The revised DLB consensus criteria now distinguish clearly between clinical features and diagnostic biomarkers, and give guidance about optimal methods to establish and interpret these. Substantial new information has been incorporated about previously reported aspects of DLB, with increased diagnostic weighting given to REM sleep behavior disorder and ¹²³iodine-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. The diagnostic role of other neuroimaging, electrophysiologic, and laboratory investigations is also described. Minor modifications to pathologic methods and criteria are recommended to take account of Alzheimer disease neuropathologic change, to add previously omitted Lewy-related pathology categories, and to include assessments for substantia nigra neuronal loss. Recommendations about clinical management are largely based upon expert opinion since randomized controlled trials in DLB are few. Substantial progress has been made since the previous report in the detection and recognition of DLB as a common and important clinical disorder. During that period it has been incorporated into DSM-5, as major neurocognitive disorder with Lewy bodies. There remains a pressing need to understand the underlying neurobiology and pathophysiology of DLB, to develop and deliver clinical trials with both symptomatic and disease-modifying agents, and to help patients and carers worldwide to inform themselves about the disease, its prognosis, best available treatments, ongoing research, and how to get adequate support.

SUBMITTER: McKeith IG

PROVIDER: S-EPMC5496518 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionA significant proportion of dementia is concretely estimated to be attributable to dementia with Lewy bodies (DLB)-one of the most common types of progressive dementia; however, there is a paucity of literature on this disease. We aimed to examine available evidence to gain a better understanding of its treatment landscape, clinical management, and disease burden.MethodsA systematic literature review captured any DLB studies that report on randomised controlled trials (RCTs), epidemiology, disease progression, and economic data. An additional targeted literature review captured studies reporting on clinical management and quality of life (QoL) in this disease. Publication date was limited to 1 January 2007-26 March 2018, with the exception for RCTs, where no time restrictions were applied.FindingsOf the 3486 studies initially identified, 55 studies were eligible for inclusion. The studies were mainly from Europe (n = 29), the USA (n = 9), and Japan (n = 8). Mini-Mental State Examination and Neuropsychiatric Inventory scores were the most commonly reported clinical outcomes in RCTs (n = 14). The most frequently identified interventions reported in RCTs were donepezil and memantine. Patients with DLB typically reported worse outcomes in relation to efficacy and safety, cognitive impairment, survival, and QoL compared with those with Alzheimer's disease (AD). Additionally, patients with DLB were associated with higher hospitalisation rates and cost of care. Furthermore, there is a reliance on a small number of consensus guidelines. Of these, only one set of guidelines (DLB Consortium) was developed specifically for DLB.ConclusionThe paucity of data indicates an unmet need in this therapy area. Although several studies look into the clinical and pathological aspects of DLB, consensus guidelines and studies on healthcare utilisation in patients with dementia have largely focused on AD. Additionally, most of the findings were made in comparison with AD.FundingEisai Inc.

Project description:Introduction:Given the challenges concerning the differential diagnosis of dementia, we investigated the possible added value of monoaminergic compounds to the standard cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers. Particularly, regarding the AD versus dementia with Lewy bodies (DLB) comparison, monoamines or their metabolites might have added discriminative value as there is a more severe neuropathological burden in the locus coeruleus of DLB patients, the principal site of noradrenaline synthesis. Methods:We applied enzyme-linked immunosorbent assay (ELISA) to analyze CSF amyloid ? peptide of 42 amino acids, total tau, and tau phosphorylated at threonine 181, in patients with AD, frontotemporal dementia, DLB/Parkinson's disease dementia, and controls. Reversed-phase high-performance liquid chromatography with electrochemical detection was implemented to study monoamine and metabolite levels in CSF and serum. Stepwise forward conditional logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic accuracy of these newly fitted models containing the most discriminative indicators of disease status. Results:Most significant differences in CSF and serum were confined to the noradrenergic system. More specifically, CSF 3-methoxy-4-hydroxyphenylglycol (MHPG) levels were higher, whereas serum MHPG levels were lower, in DLB patients compared with all other groups. Addition of CSF and serum MHPG levels to the CSF AD biomarker panel significantly increased diagnostic accuracy between DLB/Parkinson's disease dementia and AD. Interestingly, a model only including CSF and serum MHPG without the classic AD biomarker panel reached similar area under the curve values. Discussion:We hypothesize that varying degrees of neuronal loss in the locus coeruleus of DLB/Parkinson's disease dementia versus AD patients result in differentially altered MHPG levels, making this metabolite a valuable biomarker.

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Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium.

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