| 1. |
- Brunnström, Hans, et al.
(författare)
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Correlations of CSF tau and amyloid levels with Alzheimer pathology in neuropathologically verified dementia with Lewy bodies.
- 2013
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Ingår i: International Journal of Geriatric Psychiatry. - : Wiley. - 1099-1166 .- 0885-6230. ; 28:7, s. 738-744
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The presence of concomitant Alzheimer pathology has been linked to earlier death in cases with dementia with Lewy bodies (DLB). Recently, elevated cerebrospinal fluid (CSF) tau protein levels have been reported to be associated with shorter survival in clinically diagnosed DLB. Correlations between CSF biomarkers and neuropathological findings in DLB are missing. The aim of this study was to investigate correlations between CSF biomarker levels and histopathological findings, with a focus on concomitant Alzheimer pathology, in neuropathologically verified DLB cases. METHODS: The extent of neurofibrillary pathology (Braak stage), neuritic plaques (CERAD stage), Alzheimer pathology (PPAD9 stage) and cerebral amyloid angiopathy was assessed in 16 cases with DLB in whom total tau (T-tau), hyperphosphorylated tau and amyloid beta 1-42 (Aβ42) protein levels in CSF had been analyzed in vivo. Demographic and clinical data were collected. RESULTS: Both Braak and PPAD9 stages were inversely correlated with Aβ42 levels, whereas CERAD stage showed no significant correlations. Cerebral amyloid angiopathy correlated positively with T-tau and T-tau/Aβ42 ratio, and inversely with Aβ42 levels, but the group showed a very heterogeneous extent of cerebral amyloid angiopathy. CONCLUSIONS: The burden of concomitant Alzheimer pathology correlates with CSF Aβ42 but not with T-tau levels in cases with neuropathologically defined DLB. Copyright © 2012 John Wiley & Sons, Ltd.
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| 2. |
- Andersson, Maria A, et al.
(författare)
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The cognitive profile and CSF biomarkers in dementia with Lewy bodies and Parkinson's disease dementia.
- 2011
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Ingår i: International journal of geriatric psychiatry. - : Wiley. - 1099-1166 .- 0885-6230. ; 26:1, s. 100-5
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Tidskriftsartikel (refereegranskat)abstract
- Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) may be viewed as different points on a continuum reflecting the regional burden and distribution of pathology. An important clinical consideration is overlapping Alzheimer's disease (AD) pathology, since it has been reported that associated AD pathology in DLB shortens survival and leads to a more rapid cognitive decline. We aimed to investigate cerebrospinal fluid (CSF) biomarkers and the associated cognitive profile in DLB and PDD.
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| 3. |
- 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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| 4. |
- Bengtsson Lindberg, Marie, et al.
(författare)
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Evaluation of Systolic and Diastolic Hypotension in Dementia with Lewy Bodies and Alzheimer’s Disease.
- 2013
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Ingår i: Healthy Aging & Clinical Care in the Elderly. - 1179-0601. ; 5, s. 33-39
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Orthostatic hypotension (OH) can be seen in as many as 30% to 50% of the elderly population as well as in dementia. OH is part of the autonomic dysfunction in dementia with Lewy bodies (DLB) and prevalent in the majority of these patients. It is also suggested to be a negative prognostic factor for survival in DLB. A detailed interpretation of the 10-minute orthostatic blood pressure measurement has shown prolonged orthostasis in DLB compared with other dementias. The type of OH (systolic and diastolic) has not been separately investigated in different dementias. OBJECTIVES: The aims of this study were to analyze the type of orthostatic hypotension, systolic and/or diastolic, in different dementia groups compared with normal controls. PATIENTS AND METHODS: One-hundred fifty-six individuals, 52 with DLB, 50 with Alzheimer’s disease (AD), 54 AD with vascular components (ADvasc), and 62 normal controls, were included. As part of each patient’s routine clinical dementia investigation, systolic and diastolic blood pressure measurements were examined in the supine position, immediately after standing up, and after 1, 3, 5, and 10 minutes of standing. OH was defined as a blood pressure drop of 20 mmHg systolic or 10 mmHg diastolic, and the type of OH—systolic, diastolic or both—was defined. RESULTS: Orthostatic hypotension was severely underdiagnosed before the dementia investigation with only 2% to 4% in the dementia groups, while we found that 69% of DLB, 50% of ADvasc, 38% of AD, and 13% of normal controls had OH. A combination of systolic and diastolic OH was the most common type of OH both in the DLB (67%) and ADvasc (48%) groups, while systolic OH was the most common type in AD (63 %) as well as in normal controls (63%). Mini Mental State Examination scores differed significantly (P < 0.001) between the group with no OH (25.2 ± 4.8) and the group with combined systolic and diastolic OH (22.0 ± 4.8). CONCLUSION: Patients with DLB showed a greater proportion of combined systolic and diastolic hypotension. This might suggest a more complex OH than in patients with AD or elderly controls, possibly exacerbating the clinical picture in DLB. Further investigations of the relevance of these findings and the relation to clinical symptoms are needed.
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| 5. |
- Bras, Jose, et al.
(författare)
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Genetic analysis implicates APOE, SNCA and suggests lysosomal dysfunction in the etiology of dementia with Lewy bodies.
- 2014
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 23:23, s. 6139-6146
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Tidskriftsartikel (refereegranskat)abstract
- Clinical and neuropathological similarities between dementia with Lewy bodies (DLB), Parkinson's and Alzheimer's diseases (PD and AD, respectively) suggest that these disorders may share etiology. To test this hypothesis, we have performed an association study of 54 genomic regions, previously implicated in PD or AD, in a large cohort of DLB cases and controls. The cohort comprised 788 DLB cases and 2624 controls. To minimize the issue of potential misdiagnosis, we have also performed the analysis including only neuropathologically proven DLB cases (667 cases). The results show that the APOE is a strong genetic risk factor for DLB, confirming previous findings, and that the SNCA and SCARB2 loci are also associated after a study-wise Bonferroni correction, although these have a different association profile than the associations reported for the same loci in PD. We have previously shown that the p.N370S variant in GBA is associated with DLB, which, together with the findings at the SCARB2 locus, suggests a role for lysosomal dysfunction in this disease. These results indicate that DLB has a unique genetic risk profile when compared with the two most common neurodegenerative diseases and that the lysosome may play an important role in the etiology of this disorder. We make all these data available.
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| 6. |
- 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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| 7. |
- 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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| 8. |
- Gerhardsson, Lars, 1952, et al.
(författare)
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Cerebrospinal fluid/plasma quotients of essential and non-essential metals in patients with Alzheimer's disease.
- 2011
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Ingår i: Journal of neural transmission (Vienna, Austria : 1996). - : Springer Science and Business Media LLC. - 1435-1463 .- 0300-9564. ; 118:6, s. 957-62
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Tidskriftsartikel (refereegranskat)abstract
- In this study, the quotients (Q) between metal concentrations in cerebrospinal fluid (CSF) and plasma were studied in subjects with Alzheimer's disease (AD) and referents to investigate if the leakage through the blood-CSF barrier (BCB) increased with increased duration and severity of the disease. Concentrations of 18 metals (Mg, Ca, Mn, Fe, Co, Ni, Cu, Zn, Se, Rb, Sr, Mo, Cd, Sn, Sb, Cs, Hg, and Pb) were determined by ICP-MS in plasma and cerebrospinal fluid in 264 patients with AD, and in 54 healthy referents. The quotients Q (Mn), Q (Rb), Q (Sb), Q (Pb) and Q (Hg) were significantly lower (p≤0.003) and Q (Co) significantly higher (p≤0.001) in subjects with AD as compared with the controls. Subjects in a subgroup with more severe AD, showed the same pattern. The metal leakage into CSF did not increase with increased duration and/or severity of the disease. The permeability of BCB varied considerably between the studied metals with low median quotients (Q≤0.02) for Cd, Cu, Sb, Se and Zn and higher median quotients for Ca (Q~0.5) and Mg (Q~1.3), probably partly depending on differences in size and lipophilicity of metal-carrier complexes and specific carrier mechanisms.
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| 9. |
- Gro, Tangen, et al.
(författare)
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A longitudinal study of physical function in patients with early-onset dementia
- 2012
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Ingår i: Dementia and Geriatric Cognitive Disorders Extra. - : S. Karger AG. - 1664-5464. ; 2:1, s. 622-631
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of this study was to explore changes in mobility in terms of ambulation and transfer over 1 year in patients with early-onset Alzheimer's disease (EOAD), and to compare mobility in EOAD with patients with other types of early-onset dementia (EOOD). METHOD: Forty-two patients with EOAD and 30 patients with EOOD were included. All patients were home-dwelling and had mild or moderate degree of dementia. Mobility was assessed using the Timed Up and Go Test (TUG), a modified version of the Clinical Outcome Variables Scale, timed stair walking, and timed rise from the floor. RESULTS: The EOAD group performed significantly better than the EOOD group on all mobility tests. After 1 year, 25 persons with EOAD were tested again. The performance on TUG (p = 0.028) and stair walking (p = 0.02) had deteriorated at the 1-year follow-up in the EOAD group. CONCLUSION: Patients with EOAD performed better on mobility tasks than patients with EOOD, but their performance deteriorated at 1-year follow-up.
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| 10. |
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