Background And Objectives: Dementia with Lewy Bodies (DLB) is a heterogeneous disease, with variable signs and symptoms across multiple domains. We aimed to identify associations with rate of change in cognition, everyday functioning (IADL) and quality of life (QoL).
Methods: We included 121 DLB patients (69 ± 6 yrs, 14%F, MMSE: 25 ± 3) in our prospective cohort (follow-up 2 ± 1 yrs).
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View Article and Find Full Text PDFBackground: Dementia with Lewy bodies (DLB) is a complex, progressive neurodegenerative disease with considerable phenotypic, pathological, and genetic heterogeneity.
Objective: We tested if genetic variants in part explain the heterogeneity in DLB.
Methods: We tested the effects of variants previously associated with DLB (near APOE, GBA, and SNCA) and polygenic risk scores for Alzheimer's disease (AD-PRS) and Parkinson's disease (PD-PRS).
Dementia with Lewy bodies (DLB) is a neurodegenerative disease where synaptic loss and reduced synaptic integrity are important neuropathological substrates. Neuronal Pentraxin 2(NPTX2) is a synaptic protein that drives the GABAergic inhibitory circuit. Our aim was to examine if NPTX2 cerebral spinal fluid (CSF) levels in DLB patients were altered and how these levels related to other synaptic protein levels and to cognitive function and decline.
View Article and Find Full Text PDFSynaptic degeneration is an early phenomenon in Parkinson's disease (PD) pathogenesis. We aimed to investigate whether levels of synaptic proteins contactin-1 and contactin-2 in cerebrospinal fluid (CSF) of PD patients are reduced compared to dementia with Lewy bodies (DLB) patients and controls and to evaluate their relationship with α-synuclein aggregation. Contactin-1 and -2 were measured in CSF from PD patients ( 58), DLB patients ( 72) and age-matched controls ( 90).
View Article and Find Full Text PDFObjective: Early biomarkers for dementia with Lewy bodies (DLB) are lacking. To determine whether EEG differentiates the prodromal phase of DLB from other causes of mild cognitive impairment (MCI) and whether EEG is predictive for time to conversion from MCI to DLB, we compared EEGs and clinical follow-up of patients with MCI due to DLB with those of patients with MCI due to Alzheimer disease (MCI-AD).
Methods: We compared 37 patients with MCI who developed DLB during follow-up or had an abnormal I-PF-CIT SPECT scan (MCI-DLB) with 67 age-matched patients with MCI-AD.
Background: Diagnosis of dementia with Lewy bodies (DLB) is challenging, largely due to a lack of diagnostic tools. Cerebrospinal fluid (CSF) biomarkers have been proven useful in Alzheimer's disease (AD) diagnosis. Here, we aimed to identify novel CSF biomarkers for DLB using a high-throughput proteomic approach.
View Article and Find Full Text PDFObjective: The objective of this study was to examine clinical characteristics, cognitive decline, and predictors for time to dementia in prodromal dementia with Lewy bodies with mild cognitive impairment (MCI-LB) compared with prodromal Alzheimer's disease (MCI-AD).
Methods: We included 73 MCI-LB patients (12% female; 68 ± 6 years; Mini Mental State Examination, 27 ± 2) and 124 MCI-AD patients (48% female; 68 ± 7 years; Mini Mental State Examination, 27 ± 2) from the Amsterdam Dementia Cohort. Follow-up was available for 61 MCI-LB patients and all MCI-AD patients (3 ± 2 years).
It is currently unknown whether patients with dementia with Lewy bodies (DLB) with relatives with dementia or Parkinson's disease (familial DLB patients) have a different phenotype than sporadic DLB patients. In this study, we aimed to examine disease onset, rate of cognitive decline, survival, and Alzheimer's disease (AD) biomarkers in patients with familial DLB (n = 154) and sporadic DLB (n = 137), using linear mixed model analysis and Cox regression analysis, among others. Familial patients had a shorter survival (8.
View Article and Find Full Text PDFAn amendment to this paper has been published and can be accessed via a link at the top of the paper.
View Article and Find Full Text PDFBackground: One of the major challenges in diagnosing dementia with Lewy bodies (DLB) is the common co-morbid presence of amyloid pathology. To understand the putative role of altered amyloid-β (Aβ) metabolism in dementia with DLB, we analyzed levels of different cerebrospinal fluid (CSF) Aβ peptides (Aβ38, Aβ40, Aβ42) in DLB, Alzheimer's disease (AD), and cognitively normal controls.
Methods: CSF from patients with DLB (n = 72; age 68 ± 6 years; 10%F; Mini-mental State examination (MMSE) 23 ± 4), AD (n = 38; age 68 ± 6 years; 8%F; MMSE 22 ± 5), and cognitively normal controls (n = 38; age 67 ± 7 years; 13%F; MMSE 29 ± 2) was analyzed using the Meso Scale Discovery assay for human Aβ peptides.
In a previous proteomic study, we identified the neurosecretory protein VGF (VGF) as a potential biomarker for dementia with Lewy bodies (DLB). Here, we extended the study of VGF by comparing levels in cerebrospinal fluid (CSF) from 44 DLB patients, 20 Alzheimer's disease (AD) patients, and 22 cognitively normal controls selected from the Amsterdam Dementia Cohort. CSF was analyzed using two orthogonal analytical methods: (1) In-house-developed quantitative ELISA and (2) selected reaction monitoring (SRM).
View Article and Find Full Text PDFBackground: Quality of Life (QoL) is an important outcome measure in dementia, particularly in the context of interventions. Research investigating longitudinal QoL in dementia with Lewy bodies (DLB) is currently lacking.
Objective: To investigate determinants and trajectories of QoL in DLB compared to Alzheimer's disease (AD) and controls.
Dementia with Lewy Bodies (DLB) is a common neurodegenerative disorder with poor prognosis and mainly unknown pathophysiology. Heritability estimates exceed 30% but few genetic risk variants have been identified. Here we investigated common genetic variants associated with DLB in a large European multisite sample.
View Article and Find Full Text PDFBackground: The objective of this study was to investigate the discriminating value of a range of CSF α-synuclein species for dementia with Lewy bodies compared with Alzheimer's disease, PD, and cognitively normal controls.
Methods: We applied our recently published enzyme-linked immunosorbent assays to measure the CSF levels of total α-synuclein, oligomeric α-synuclein, and phosphorylated α-synuclein in dementia with Lewy bodies (n = 42), Alzheimer's disease (n = 39), PD (n = 46), and controls (n = 78). General linear models corrected for age and sex were performed to assess differences in α-synuclein levels between groups.
: Previous studies on electroencephalography (EEG) to discriminate between dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) have been promising. These studies did not consider the pathological overlap of the two diseases. DLB-patients with concomitant AD pathology (DLB/AD+) have a more severe disease manifestation.
View Article and Find Full Text PDFParkinsonism Relat Disord
October 2017
The genetic architecture of dementia with Lewy bodies (DLB) is increasingly taking shape. Initially, genetic research focused mainly on linkage and candidate gene studies in small series of DLB patients. More recently, association and exome sequencing studies in larger groups have been conducted, and have shown that several variants in GBA and the APOE ε4 allele are important genetic risk factors for DLB.
View Article and Find Full Text PDFBackground: Concomitant Alzheimer's disease (AD) pathology is observed in Lewy body diseases (LBD), but the clinical impact is unknown. Only a few biomarker studies in LBD exist and have included small cohorts from single centers.
Objective: We aimed to evaluate the prevalence of abnormal cerebrospinal fluid (CSF) AD biomarkers across the spectrum of LBD in a large multicenter cohort and to assess whether an AD biomarker profile was associated with demographic and clinical differences in dementia with Lewy bodies (DLB).
Introduction: Alzheimer's disease pathologies are common in dementia with Lewy bodies, but their clinical relevance is not clear. CSF biomarkers amyloid beta 1-42, total tau, and tau phosphorylated at threonine 181 reflect Alzheimer's disease neuropathology antemortem. In PD, low CSF amyloid beta 1-42 predict long-term cognitive decline, but little is known about these biomarkers as predictors for cognitive decline in Lewy body dementia.
View Article and Find Full Text PDFCognitive impairment is one of the earliest, most common, and most disabling non-motor symptoms in Parkinson's disease (PD). Thus, routine screening of global cognitive abilities is important for the optimal management of PD patients. Few global cognitive screening instruments have been developed for or validated in PD patients.
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