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. |
- Londos, Elisabet, et al.
(författare)
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Extreme sleep pattern in Lewy body dementia : A hypothalamic matter?
- 2019
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Ingår i: BMJ Case Reports. - : BMJ. - 1757-790X. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Excessive sleep during the night and for >2 hours during the day is part of the fluctuating wakefulness criterion of dementia with Lewy bodies (DLB). The phenomenon â € sleep days' is not uncommon in nursing homes. Here, we describe a woman who, for months, slept for 3 days and nights in a row and thereafter was awake for 3 days and nights. Electroencephalogram (EEG) showed slow background activity and increased delta activity. No epileptiform activity was detected. Polysomnography showed a severely disturbed, markedly fragmented sleep pattern. On her death, neuropathology revealed degeneration and loss of neurons along with α-synuclein-containing Lewy body inclusions and neurites in the substantia nigra, locus coeruleus, hypothalamus, and neocortex, thus fulfilling the criteria of DLB, cortical type. We propose that the hypothalamic degeneration contributed significantly to the clinical profile in this case. We suggest that patients with sleep days should be investigated for other DLB signs.
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3. |
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4. |
- Abdelnour, C., et al.
(författare)
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Alzheimer's disease cerebrospinal fluid biomarkers predict cognitive decline in lewy body dementia
- 2016
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 31:8, s. 1203-1208
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionAlzheimer'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. The aim of this study was to assess whether Alzheimer's disease CSF biomarkers predict cognitive decline in Lewy body dementia. MethodsFrom a large European dementia with Lewy bodies multicenter study, we analyzed baseline Alzheimer's disease CSF biomarkers and serial MMSE (baseline and 1- and 2-year follow-up) in 100 patients with Lewy body dementia. Linear mixed-effects analyses, adjusted for sex, age, baseline MMSE, and education, were performed to model the association between CSF biomarkers and rate of cognitive decline measured with MMSE. An Alzheimer's disease CSF profile was defined as pathological amyloid beta 1-42 plus pathological total tau or phosphorylated tau. ResultsThe Alzheimer's disease CSF profile, and pathological levels of amyloid beta 1-42, were associated with a more rapid decline in MMSE (2.2 [P < 0.05] and 2.9 points difference [P < 0.01], respectively). Higher total tau values showed a trend toward association without statistical significance (2.0 points difference; P = 0.064), whereas phosphorylated tau was not associated with decline. ConclusionsReduced levels of CSF amyloid beta 1-42 were associated with more rapid cognitive decline in Lewy body dementia patients. Future prospective studies should include larger samples, centralized CSF analyses, longer follow-up, and biomarker-pathology correlation. (c) 2016 International Parkinson and Movement Disorder Society
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5. |
- Andersson, Maria A, et al.
(författare)
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Electroencephalogram variability in dementia with lewy bodies, Alzheimer's disease and controls.
- 2008
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 26:3, s. 284-290
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIM: Dementia with Lewy bodies (DLB) is probably still underdiagnosed in the clinical setting. Previous studies have suggested a relationship between fluctuations in attention and electroencephalogram (EEG) measures. Since fluctuation in attention is a core symptom of DLB, we sought to further explore whether EEG measures could help differentiate DLB from Alzheimer's disease (AD) and healthy controls. METHODS: The EEGs of 20 patients with DLB, 64 patients with AD and 54 elderly controls were assessed in regard to frequencies, coherence, and variability. RESULTS: Greater variability was seen in delta-band power over 2-second intervals in parietal electrodes of DLB patients. The DLB group had a higher degree of overall coherence in the delta band and a lower degree of overall coherence in the alpha band than the other groups. Finally, EEG measures could distinguish DLB patients from AD patients and controls with areas under the receiver operating characteristic curves ranging between 0.75 and 0.80 and between 0.91 and 0.97, respectively. CONCLUSIONS: We suggest that the difference in variability may be associated with the fluctuating cognition seen in DLB. This might have clinical implications as guidance in the diagnosis of DLB. The EEG analysis is simple enough to be possible to apply in clinical practice.
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6. |
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7. |
- 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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8. |
- Andersson, M, et al.
(författare)
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The period of hypotension following orthostatic challenge is prolonged in dementia with Lewy bodies.
- 2008
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Ingår i: International Journal of Geriatric Psychiatry. - : Wiley. - 1099-1166 .- 0885-6230. ; 23:2, s. 192-198
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To determine whether orthostatic hypotension (OH) is more common in patients with dementia than in older people without cognitive impairment and to identify key differences in the profile of the orthostatic response and the pulse drive during orthostatic challenge between Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). METHODS: The orthostatic response was evaluated in 235 patients with AD, 52 patients with DLB and 62 elderly controls. The blood pressure and pulse rate were measured in supine position, immediately after standing up and after 1, 3, 5 and 10 min of standing. OH was defined as a reduction of systolic blood pressure (SBP) of at least 20 mm Hg or a reduction of diastolic blood pressure (DBP) of at least 10 mm Hg. RESULTS: OH occurred in 69% of the DLB patients and in 42% of the AD patients, but only in 13% of the controls (p < 0.001 controls vs AD and controls vs DLB, p = 0.001 AD vs DLB) The DLB patients had a greater drop in SBP than the other study groups during orthostatic challenge and had a more prolonged period of orthostasis. The pulse drive on orthostatic challenge was similar in between groups. However, in the DLB group it was not adequate to restore the blood pressure to supine values. CONCLUSIONS: Patients with DLB react different to orthostatic challenge than patients with AD or controls, with important clinical implications for key disease symptoms and treatment.
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9. |
- 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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10. |
- 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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11. |
- Bengtsson Lindberg, Marie, et al.
(författare)
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Lack of orthostatic symptoms in dementia patients with orthostatic hypotension.
- 2015
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Ingår i: Clinical Autonomic Research. - : Springer Science and Business Media LLC. - 1619-1560 .- 0959-9851. ; 25:2, s. 87-94
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Orthostatic hypotension (OH) is common and increases with age. OH is part of the autonomic dysfunction in dementia with Lewy bodies (DLB). Commonly OH is diagnosed when the patient falls which is a risk factor of premature death. Our objective was to systematically investigate the clinical symptoms associated with measurement of OH in different neurodegenerative dementias and normal controls (NC). Methods: 154 patients [50 DLB, 50 Alzheimer’s disease (AD), 54 AD and vascular components (ADvasc)] were examined with systolic and diastolic blood pressure measurements in supine position, immediately after standing up and after 1, 3, 5 and 10 min of standing. They were compared with 50 NC. Orthostatic symptoms were registered according to a predefined protocol. Results: Twenty-seven percent of all the investigated individuals reported OH symptoms during the measurement while 43% fulfilled the criteria of OH. Sixty-three percent of orthostatic patients did not have any symptoms during the measurement. The prevalence of any orthostatic symptoms during the measurement differed significantly (p<0.001) between the diagnostic groups with 40% in DLB patients, 37% in ADvasc, 28% in AD and 2% in NC. The most frequent symptom was dizziness 13.7%. Conclusions: Classical orthostatic symptoms are absent in the majority of dementia patients with OH. The orthostatic reaction must therefore be routinely measured in this patient group. This is particularly important for patients with DLB where falls as a result of OH are common.
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12. |
- Boström, Fredrik, et al.
(författare)
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Cerebrospinal fluid total tau is associated with shorter survival in dementia with Lewy bodies.
- 2009
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 28:4, s. 314-9
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Tidskriftsartikel (refereegranskat)abstract
- A pathology typical of dementia with Lewy bodies (DLB) has been demonstrated to increase mortality to a greater extent than the pathology of Alzheimer's disease (AD). However, mortality in DLB has also been shown to increase with concomitant AD pathology. Furthermore, in a recent publication, we showed that there is a robust and specific increase in CSF calcium and magnesium in DLB patients compared to both AD patients and controls. Thus, in order to explore the influence of CSF AD markers and trace element concentrations on mortality in DLB, we undertook a longitudinal prospective study of 47 clinically diagnosed DLB patients and 157 AD patients as well as 49 healthy volunteers. Both AD and DLB patients showed an increased mortality compared to the healthy controls (relative risk: 10 and 8, respectively; p < 0.001). Increased levels of CSF total tau were associated with increased mortality among the DLB patients (p < 0.05), but not among the AD patients or controls. Gender, age, MMSE score, Abeta42 concentration and phosphorylated tau, and CSF trace element concentrations did not influence survival in the obtained models.
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13. |
- Boström, Fredrik, et al.
(författare)
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CSF Mg and Ca as diagnostic markers for dementia with Lewy bodies.
- 2008
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Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 30:8, s. 1265-1271
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Tidskriftsartikel (refereegranskat)abstract
- Accumulating evidence implicates a role for altered metal homeostasis in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). However, few investigations have addressed this issue in dementia with Lewy bodies (DLB). The aim of the present study was to investigate metal concentrations in cerebrospinal fluid (CSF) and plasma from patients with DLB and other neurodegenerative disorders. To that end, CSF and plasma samples were collected from 29 patients with DLB, 174 patients with AD, 90 patients with AD with minor vascular components, and 51 healthy volunteers. Total concentrations of Mg, Ca, Mn, Fe, Cu, Zn, Rb, Sr, and Cs were determined using mass spectrometry. Patients with DLB had elevated Ca and Mg levels in CSF and Mg levels in plasma as compared to all other groups (p<0.001). Furthermore, a combination of CSF-Mg and CSF-Ca could distinguish DLB from AD with a sensitivity of 93% and a specificity of 85%. Cu levels in both CSF and plasma tended to be higher in DLB compared to the other groups, but these trends failed to reach significance after correction for multiple comparisons. Mn, Fe, Zn, Rb, and Sr concentration in CSF or plasma were similar in all groups. The observed elevations of CSF-Mg, CSF-Ca and CSF-Cu may contribute to or be associated with the neurodegenerative process in DLB. Furthermore, determination of CSF-Mg and CSF-Ca concentration may be a valuable tool in distinguishing DLB from AD.
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15. |
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16. |
- Boström, Fredrik, et al.
(författare)
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Patients with Lewy body dementia use more resources than those with Alzheimer's disease.
- 2007
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Ingår i: International Journal of Geriatric Psychiatry. - : Wiley. - 1099-1166 .- 0885-6230. ; 22:Dec 29, s. 713-719
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Forskningsöversikt (refereegranskat)abstract
- Objectives The purpose of this study was to compare resource use and costs in patients with dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) and to assess determinants of costs of care in DLB. Method Thirty-four patients with DLB were included in a cross-sectional study. The patients were matched with respect to age, gender and Mini Mental State Examination (MMSE) score to 34 patients with AD. Both groups were examined using Resource Utilisation in Dementia (RUD Lite), MMSE and the Neuropsychiatric inventory (NPI). The DLB patients were additionally examined using the Disability Assessment for Dementia Scale (DAD). Results Costs of care in patients suffering from DLB was on average 348,000 SEK (37,5004 is an element of) per year compared to 169,000 SEK (18,2004 is an element of) in the AD group (p < 0.001). Within the DLB group, care costs correlated significantly (r(c) = 2.77, p < 0.001) with dependency in instrumental activities of daily living measured with DAD, whereas MMSE and NPI were not significantly correlated to resource use in the DLB group. Conclusions DLB patients use more resources, and are more costly than AD patients. Dependency in instrumental activities of daily living is strongly correlated to resource use in DLB patients. Copyright (c) 2006 John Wiley & Sons, Ltd.
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17. |
- 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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18. |
- Brundin, Patrik, et al.
(författare)
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Dopamine neurons grafted unilaterally to the nucleus accumbens affect drug-induced circling and locomotion
- 1987
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Ingår i: Experimental Brain Research. - 0014-4819. ; 69:1, s. 183-194
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the present study was to investigate the amplifying function of the nucleus accumbens septi region (NAS) in 6-hydroxydopamine (6-OHDA)-induced rotational behaviour by implanting fetal dopamine (DA)-rich mesencephalic cell suspensions unilaterally in the NAS of rats previously subjected to combined mesostriatal (MS) and NAS 6-OHDA lesions. First, all the rats received a unilateral 6-OHDA lesion of the ascending MS DA pathway, which produced an amphetamine-induced rotational asymmetry towards the lesioned side. In a second step, the rats received a local bilateral 6-OHDA lesion of the NAS which, as previously shown, caused a significant attenuation of the amphetamine-induced locomotor (1.5 mg/kg) and rotational (5 mg/kg) behaviour. Finally, some of these MS + NAS lesioned rats received a unilateral mesencephalic DA graft into the NAS ipsilateral to the original MS lesion. The unilateral DA-rich grafts in the NAS significantly elevated the amphetamine-induced locomotion and ipsilateral circling (opposite to the direction of rotation produced when a graft is placed in the ipsilateral caudate-putamen), suggesting that the NAS plays only an amplifier role in locomotor behaviour and not a directional role. In addition, these grafts significantly attenuated the supersensitive locomotor response observed in lesioned rats when given apomorphine (0.05 mg/kg). The findings emphasize the amplifying role of the NAS in locomotion and circling behaviour and they extend previous findings demonstrating the functional heterogeneity of the striatal complex as well as the regional specificity of the graft-derived functional effects. Moreover, the results argue against the notion that DA grafts can function through a diffusion of transmitter over large distances since, despite the large size of the grafts, the functional graft effects were well localized to the reinnervated NAS and ventromedial striatal regions. We conclude, therefore, that graft-induced amelioration of postural and locomotor deficits are affected through different parts of the striatal complex, and that multiple graft placements are required to produce more complete recovery of motoric behaviour in the DA-depleted brain.
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19. |
- Buchhave, Peder, et al.
(författare)
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Longitudinal study of CSF biomarkers in patients with Alzheimer's disease.
- 2009
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 16:Suppl 3, s. 337-337
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The CSF biomarkers tau and Abeta42 can identify patients with AD, even during the preclinical stages. However, previous studies on longitudinal changes of tau and Abeta42 in individual patients with AD and elderly controls report somewhat inconsistent results. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the levels of tau and Abeta42 at baseline and after 1 year in 100 patients with AD. In a second cohort of 45 AD patients we measured the CSF biomarkers at baseline and after 2 years. Moreover, in 34 healthy elderly controls the CSF biomarkers were followed for 4 years. The baseline levels of tau were increased with >60% in AD patients compared to controls (p<0.001), while baseline Abeta42 levels were decreased with >50% (p<0.001). In the AD group followed for 2 years, tau increased with 16% compared to the baseline levels (p<0.05). However, the levels of tau were stable over 4 years in the controls. The levels of Abeta42 did not change significantly over time in any of the groups. In the patients with AD, tau was moderately associated with worse cognitive performance already at baseline (p<0.05). CONCLUSIONS/SIGNIFICANCE: Tau and Abeta42 in CSF seem to reflect the underlying disease state in both early and late stages of AD. The slight increase in tau over time observed in the patients with AD is modest when compared to the relatively large difference in absolute tau levels between AD patients and controls. Therefore, these markers maintain their usefulness as state markers over time and might serve as surrogate markers for treatment efficacy in clinical trials.
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20. |
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21. |
- 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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22. |
- 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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23. |
- 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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24. |
- Fälth, Nils, et al.
(författare)
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Choral Singing Enriches Everyday Life for People With Mild to Moderate Dementia and Their Family Caregivers
- 2022
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Ingår i: Journal of Psychosocial Nursing and Mental Health Services. - : SLACK, Inc.. - 0279-3695 .- 1938-2413. ; 60:5, s. 29-36
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Tidskriftsartikel (refereegranskat)abstract
- Dementia causes substantial suffering for affected persons and their family care-givers. Because no cure is available, it is important to investigate how alternative therapies can improve life for these individuals. For the current study, persons with dementia (PwD) were recruited from a specialized Memory Clinic in Sweden to en-gage in a choral singing intervention for 1 hour per week for four semesters. PwD were encouraged to bring a family caregiver to the sessions; both were interviewed and data were analyzed using qualitative content analysis. The choral singing intervention appeared to become an important social context for PwD and family caregivers and had a positive impact on relationship, mental well-being, mood, and memory. The intervention appeared to act as an enriched environment for all participants. Choral singing interventions for PwD and their family caregivers is a simple means to create a social context and improve general well-being.
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25. |
- 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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