| 1. |
- Ballard, Clive, et al.
(författare)
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alpha-synuclein antibodies recognize a protein present at lower levels in the CSF of patients with dementia with Lewy bodies
- 2010
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Ingår i: International Psychogeriatrics. - 1741-203X. ; 22:2, s. 321-327
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dementia with Lewy bodies (DLB) accounts for 15-20%, of the millions of people worldwide with dementia. Accurate diagnosis is essential to avoid harm and optimize clinical management. There is therefore an urgent need to identify reliable biomarkers. Methods: Mass spectrometry was used to determine the specificity of antibody alpha-synuclein (211) for alpha-synuclein. Using gel electrophoresis we measured protein levels detected by alpha-synuclein specific antibodies in the cerebrospinal fluid (CSF) of DLB patients and compared them to age matched controls. Results: A 24 kDa band was detected using alpha-synuclein specific antibodies which was significantly reduced in the CSF of DLB patients compared to age matched controls (p < 0.05). Further analysis confirmed that even DLB patients with mild dementia showed significant reductions in this protein in comparison to controls. Conclusions: The current study emphasizes the necessity for further studies of CSF alpha-synuclein as a biomarker of DLB and extends our previous knowledge by establishing a potential relationship between alpha-synuclein and the severity of cognitive impairment. The identification of this 24 kDa protein is the next important step in these studies.
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| 2. |
- Creese, Byron, et al.
(författare)
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Determining the Association of the 5HTTLPR Polymorphism with Delusions and Hallucinations in Lewy Body Dementias
- 2014
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Ingår i: The American Journal of Geriatric Psychiatry. - : Elsevier BV. - 1545-7214 .- 1064-7481. ; 22:6, s. 580-586
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To determine whether the 5HTTLPR serotonin transporter polymorphism is associated with delusions and hallucinations in people with dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD). Design: Prospective cohort study. Participants: A total of 187 individuals, recruited from centres in Norway, Sweden, and the United Kingdom were included in this study; 97 with clinically or neuropathologically diagnosed DLB/PDD and 90 cognitively normal individuals as a comparison group. Measurements: All participants with dementia underwent serial evaluation of neuropsychiatric symptoms to assess the presence of persistent delusions and hallucinations using the Columbia University Scale for Psychopathology in Alzheimer disease, the Neuropsychiatric Inventory, or the Present Behavioural Examination. Severity of cognitive impairment was measured using the Mini Mental State Examination (MMSE). Individuals were genotyped for the 5HTTLPR polymorphism. Results: Logistic regression demonstrated that homozygosity for the L/L genotype and lower MMSE were associated with an increased risk for delusions (odds ratio: 11.5 and 1.16, respectively). Neither was significantly associated with hallucinations. Conclusions: This study is the first to demonstrate the 5HTTLPR polymorphism is associated with delusions in Lewy body dementias, with important implications regarding the mechanisms underlying this symptom across the AD/DLB/PDD spectrum. Further studies are warranted to investigate this relationship further and examine treatment opportunities.
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| 3. |
- Creese, Byron, et al.
(författare)
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No association of COMT val158met polymorphism and psychotic symptoms in Lewy body dementias
- 2012
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Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 531:1, s. 1-4
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Tidskriftsartikel (refereegranskat)abstract
- We sought to determine whether the COMT val158met polymorphism (rs4680) is associated with delusions and hallucinations in people with dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). A total of 218 individuals, recruited from centres in Norway, Sweden and the UK were included in this study; 121 with clinically or neuropathologically diagnosed DLB/PDD and 97 age-matched, cognitively normal controls. All participants with dementia underwent serial evaluation of neuropsychiatric symptoms to assess the presence of persistent delusions and hallucinations using the Columbia University Scale for Psychopathology in Alzheimer's disease, the Neuropsychiatric Inventory or the Present Behavioural Examination. Severity of cognitive impairment was measured using the Mini Mental State Examination (MMSE). Both controls and participants with dementia were genotyped for rs4680. In contrast to previous findings, analysis by logistic regression failed to find any associations between rs4680 and psychotic symptoms. Larger studies in well characterised cohorts are warranted in order to investigate this relationship further. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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| 4. |
- Ferreira, Daniel, et al.
(författare)
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β-Amyloid and tau biomarkers and clinical phenotype in dementia with Lewy bodies
- 2020
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Ingår i: Neurology. - 1526-632X. ; 95:24, s. 3257-3268
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In a multicenter cohort of probable dementia with Lewy bodies (DLB), we tested the hypothesis that β-amyloid and tau biomarker positivity increases with age, which is modified by APOE genotype and sex, and that there are isolated and synergistic associations with the clinical phenotype. METHODS: We included 417 patients with DLB (age 45-93 years, 31% women). Positivity on β-amyloid (A+) and tau (T+) biomarkers was determined by CSF β-amyloid1-42 and phosphorylated tau in the European cohort and by Pittsburgh compound B and AV-1451 PET in the Mayo Clinic cohort. Patients were stratified into 4 groups: A-T-, A+T-, A-T+, and A+T+. RESULTS: A-T- was the largest group (39%), followed by A+T- (32%), A+T+ (15%), and A-T+ (13%). The percentage of A-T- decreased with age, and A+ and T+ increased with age in both women and men. A+ increased more in APOE ε4 carriers with age than in noncarriers. A+ was the main predictor of lower cognitive performance when considered together with T+. T+ was associated with a lower frequency of parkinsonism and probable REM sleep behavior disorder. There were no significant interactions between A+ and T+ in relation to the clinical phenotype. CONCLUSIONS: Alzheimer disease pathologic changes are common in DLB and are associated with the clinical phenotype. β-Amyloid is associated with cognitive impairment, and tau pathology is associated with lower frequency of clinical features of DLB. These findings have important implications for diagnosis, prognosis, and disease monitoring, as well as for clinical trials targeting disease-specific proteins in DLB. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with probable DLB, β-amyloid is associated with lower cognitive performance and tau pathology is associated with lower frequency of clinical features of DLB.
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| 5. |
- Jones, Emma L., et al.
(författare)
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A Pilot Study Examining Associations between DYRK1A and alpha-Synuclein Dementias
- 2012
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Ingår i: Neurodegenerative Diseases. - : S. Karger AG. - 1660-2862 .- 1660-2854. ; 10:1-4, s. 229-231
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Tidskriftsartikel (refereegranskat)abstract
- Background: DYRK1A is a kinase targeting several proteins associated with the pathology of dementias, including alpha-synuclein and amyloid precursor protein. It is not clear if DYRK1A genetics are associated with neurodegenerative conditions. Objective: To determine if DYRK1A also has a genetic association with alpha-synuclein dementias such as dementia with Lewy bodies and Parkinson's disease dementia. Methods: DNA samples from prospectively followed cohorts of control and dementia individuals were genotyped for the DYRK1A rs8126696 polymorphism. Results: The rs8126696 polymorphism altered the risk of developing an alpha-synuclein-associated dementia. Conclusion: DYRK1A could prove to be an important therapeutic target as it interacts with several proteins associated with the development of pathology in dementia. Copyright (C) 2012 S. Karger AG, Basel
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| 6. |
- Kramberger, Milica G., et al.
(författare)
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Long-Term Cognitive Decline in Dementia with Lewy Bodies in a Large Multicenter, International Cohort
- 2017
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 57:3, s. 787-795
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Tidskriftsartikel (refereegranskat)abstract
- Background/Objective: The aim of this study was to describe the rate and clinical predictors of cognitive decline in dementia with Lewy bodies (DLB), and compare the findings with Alzheimer's disease (AD) and Parkinson's disease dementia (PDD) patients. Methods: Longitudinal scores for the Mini-Mental State Examination (MMSE) in 1,290 patients (835 DLB, 198 PDD, and 257 AD) were available from 18 centers with up to three years longitudinal data. Linear mixed effects analyses with appropriate covariates were used to model MMSE decline over time. Several subgroup analyses were performed, defined by anti-dementia medication use, baseline MMSE score, and DLB core features. Results: The mean annual decline in MMSE score was 2.1 points in DLB, compared to 1.6 in AD (p=0.07 compared to DLB) and 1.8 in PDD (p=0.19). Rates of decline were significantly higher in DLB compared to AD and PDD when baseline MMSE score was included as a covariate, and when only those DLB patients with an abnormal dopamine transporter SPECT scan were included. Decline was not predicted by sex, baseline MMSE score, or presence of specific DLB core features. Conclusions: The average annual decline in MMSE score in DLB is approximately two points. Although in the overall analyses there were no differences in the rate of decline between the three neurodegenerative disorders, there were indications of a more rapid decline in DLB than in AD and PDD. Further studies are needed to understand the predictors and mechanisms of cognitive decline in DLB.
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| 7. |
- Larsson, Victoria, et al.
(författare)
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Quality of Life and the Effect of Memantine in Dementia with Lewy Bodies and Parkinson's Disease Dementia.
- 2011
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 32:4, s. 227-234
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To investigate quality of life (QOL) and the effect of memantine treatment in patients with Lewy body dementias. Methods: A secondary analysis of a randomized controlled study in 70 patients with Parkinson's disease dementia (PDD) or dementia with Lewy bodies (DLB) over 24 weeks using caregiver-rated QOL-Alzheimer's disease (AD) in domains according to the WHO's classification of health. Results: Baseline QOL shows lower ratings for body functions over environmental factors in DLB/PDD. Treatment with memantine significantly improves life as a whole compared to placebo and improves total QOL, body function and structure. Conclusion: This study shows that memantine improves QOL in Lewy body dementias. We also demonstrate important QOL patterns which can be used in clinical practice. Copyright (C) 2011 S. Karger AG, Basel
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| 8. |
- Larsson, Victoria, et al.
(författare)
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The effect of memantine on sleep behaviour in dementia with Lewy bodies and Parkinson's disease dementia.
- 2010
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Ingår i: International Journal of Geriatric Psychiatry. - : Wiley. - 1099-1166 .- 0885-6230. ; 25:10, s. 1030-1038
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Two common and characteristic sleep disturbances have been described in dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD); excessive daytime sleepiness and REM sleep behaviour disorder (RBD). This study is an analysis of a secondary outcome measure of a larger study already reported, aimed to determine whether memantine has an effect on the sleep disturbances in DLB and PDD patients. METHODS: Patients with DLB or PDD were included in a placebo-controlled, randomised controlled study of memantine (20 mg per day) for 24 weeks. The Stavanger Sleep Questionnaire and the Epworth Sleepiness Scale were used to evaluate the effect on sleep disturbances. RESULTS: Forty two patients started treatment; 20 with memantine and 22 with placebo. The primary analysis was the comparison of change between the two groups during a 24-week period, using the modified ITT population (last observation carried forward). At 24 weeks, patients treated with memantine were less physically active during sleep while patients in the placebo group worsened. Mean difference between the groups (0.5 [0.05-0.90]) was significant (p = 0.006). No significant change was observed in severity of excessive daytime sleepiness. CONCLUSIONS: Memantine decreases probable REM sleep behaviour disorder in patients with DLB and PDD. Both diagnostic groups contributed equally to the outcome.
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| 9. |
- Mulugeta, Ezra, et al.
(författare)
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Cerebrospinal Fluid Levels of sAPPα and sAPPβ in Lewy Body and Alzheimer's Disease: Clinical and Neurochemical Correlates.
- 2011
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Ingår i: International journal of Alzheimer's disease. - : Hindawi Limited. - 2090-0252. ; 2011
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Tidskriftsartikel (refereegranskat)abstract
- We measured cerebrospinal fluid (CSF) levels of the soluble isoforms of amyloid precursor protein (APP; sAPPα sAPPβ) and other CSF biomarkers in 107 patients with Alzheimer's disease (AD), dementia with Lewy body dementia (DLB), Parkinson's disease dementia (PDD), and normal controls (NC) using commercial kits. DLB and PDD were combined in a Lewy body dementia group (LBD). No differences were observed in sAPPα and sAPPβ levels between the groups. Significant correlations were observed between sAPPα and sAPPβ and between sAPPβ and Mini-Mental State Examination scores in the total group analysis as well as when LBD and AD groups were analyzed separately. sAPPα and sAPPβ levels correlated with Aβ38, Aβ40, Aβ42, and Tau in the LBD group. In AD, sAPPα correlated with p-Tau and sAPPβ with Aβ40. The differential association between sAPPα and sAPPβ with Aβ and Tau species between LBD and AD groups suggests a possible relationship with the underlying pathologies in LBD and AD.
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| 10. |
- Mulugeta, Ezra, et al.
(författare)
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CSF amyloid {beta}38 as a novel diagnostic marker for dementia with Lewy bodies.
- 2011
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Ingår i: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 82:2, s. 160-4
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Tidskriftsartikel (refereegranskat)abstract
- Background The clinical distinction between Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) is sometimes difficult, particularly in mild cases. Although CSF markers such as amyloid β42 (Aβ42) and P-tau can distinguish between AD and normal controls, their ability to distinguish between AD and DLB is not adequate. Objective This study aims to investigate whether CSF markers, in particular levels of Aβ38, can differentiate between mild AD and DLB. Methods 85 individuals were included after standardised diagnostic procedures: 30 diagnosed as probable AD, 23 probable DLB, 20 probable Parkinson's disease dementia and 12 non-demented control subjects. CSF levels of Aβ38, Aβ40 and Aβ42 were determined using commercially available ultra-sensitive multi-array kit assay (MSD) for human Aβ peptides. Total tau (T-tau) and phosphorylated tau (P-tau) were analysed using ELISA (Innotest). In addition, combinations (Aβ42/Aβ38, Aβ42/Aβ40, Aβ42/P-tau and Aβ42/Aβ38/P-tau) were assessed. Results Significant between group differences were found for all CSF measures, and all except Aβ40, Aβ42 and Aβ42/P-tau differed between AD and DLB. The Aβ42/Aβ38 ratio was the measure that best discriminated between AD and DLB (AUC 0.765; p<0.005), with a sensitivity of 78% and a specificity of 67%. Conclusion This study suggests that the level of Aβ38 can potentially contribute in the diagnostic distinction between AD and DLB when combined with Aβ42. Single measures had low diagnostic accuracy, suggesting that developing a panel of markers is the most promising strategy. Studies with independent and larger samples and a priori cut-offs are needed to test this hypothesis.
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