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| 2. |
- Haglund, Mattias, et al.
(författare)
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Progressive QTc prolongation and reduced heart rate variability in dementia with Lewy bodies compared to Alzheimer's disease
- 2024
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Ingår i: Parkinsonism and Related Disorders. - 1353-8020. ; 122
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Autonomic dysfunction (AuD) is a significant clinical challenge in patients with Dementia with Lewy Bodies (DLB). Manifestations of AuD such as orthostatic hypotension (OH) is associated with falls and decreased quality of life. Cardiac autonomic denervation is an early phenomenon in DLB and a potential contributor to OH. This retrospective study was undertaken to explore whether routine ECG tracings could be used to identify signs of autonomic dysfunction in DLB. Methods: 18 patients with DLB and 18 age-matched patients with Alzheimer's disease (AD) were included. ECGs and clinical data were analyzed retrospectively for heart rate variability (HRV) and QTc interval prolongation. Results: During an average of 10 years observation time (first to last ECG recording), the QTc interval increased in the DLB group, but not in the AD group. HRV was significantly lower at end of follow-up in the DLB group than in the AD group. DLB patients with OH had greater QTc prolongation. Conclusion: Longitudinal ECG analysis indicates that signs of AuD in DLB are reflected on routine ECG tracings. If confirmed in larger cohorts, this could influence risk stratification and help direct preventive measures.
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| 3. |
- Javanshiri, Keivan, et al.
(författare)
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Atherosclerosis, Hypertension, and Diabetes in Alzheimer's Disease, Vascular Dementia, and Mixed Dementia : Prevalence and Presentation
- 2018
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877. ; 65:4, s. 1247-1258
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease (AD) is the most prevalent cause of dementia with vascular dementia (VaD) being second alongside with mixed AD and VaD, according to some. For some time, it has been proposed that cardiovascular disease (CaVD), hypertension, and diabetes mellitus (DM), which are known risk factors for VaD, also are associated with and contribute to the development of AD. Objective: The aim of this study was to investigate the prevalence of these proposed general risk factors, and to document presence of CaVD as evidenced from clinical records or from autopsy findings, further to correlate these with the diagnoses AD, VaD and mixed AD-VaD (MD), respectively. Methods: Autopsy reports at the Clinical Department of Pathology in Lund from 1992-2017 were analyzed. All cases with a complete autopsy report and a neuropathologically diagnosed dementia disorder (AD, VaD, or MD) were selected on the condition of a clinical diagnosis of dementia. Clinical data were retrieved through medical records and the Swedish National Diabetes Register (NDR). A total of 268 subjects were included. Results: In AD, there was less CaVD as significantly less organ/tissue findings (p < 0.05), significantly less hypertension (p < 0.001), and likewise significantly less DM (p = 0.0014) than in VaD, with the MD group results being set between these two in all aspects studied. Conclusion: AD and VaD exhibit such different profiles of organ and vascular damage as well as of hypertension and DM that they clearly point toward different pathogenic origin with low likelihood of shared risk factors.
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| 4. |
- Javanshiri, Keivan, et al.
(författare)
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Cardiac Alpha-Synuclein Is Present in Alpha-Synucleinopathies
- 2022
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Ingår i: Journal of Parkinson's Disease. - 1877-718X. ; 12:4, s. 1125-1131
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alpha-synucleinopathies (AS) are characterized by pathologic aggregations of alpha-synuclein (α-syn) in the central nervous system, and comprise dementia with Lewy bodies, Parkinson's disease, and multiple system atrophy. Previous studies on AS have reported findings of α-syn pathology in the peripheral nervous system of multiple organs, including the heart.Objective: The aim of this study was to further investigate and confirm the presence of cardiac α-syn in AS compared to other major neurocognitive disorders in a neuropathologically confirmed cohort.Methods: All deceased patients with performed autopsy and with neuropathologically confirmed AS at the Clinical Department of Pathology in Lund 2010-May 2021 were evaluated for inclusion. Cases with insufficiently sampled cardiac tissue or only limited neuropathological investigation were excluded. An age-matched group of individuals with other neurodegenerative diseases, having no α-syn in the CNS, served as controls. In total, 68 AS and 32 control cases were included in the study. Immunohistochemistry for detection of cardiac α-syn aggregates was performed.Results: The AS group had a significantly higher prevalence of cardiac α-syn pathology (p≤0.001) than the control group, 82% and 0%, respectively.Conclusion: This study confirms the association between AS and the presence of cardiac α-syn in a neuropathologically confirmed cohort. This motivates further research on potential pathophysiological effects on cardiac function in AS patients.
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| 5. |
- Javanshiri, Keivan
(författare)
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Cardiac and vascular pathology in Lewy body disease and Alzheimer's disease: exploring neurocognitive disorder beyond the brain
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The first aim of this thesis was to evaluate the prevalence of cardiovascular disease (CaVD), hypertension (HT), and type 2 diabetes mellitus (T2DM) in the neurodegenerative disorders Alzheimer’s disease (AD) and Lewy body disease (LBD). These conditions are considered modifiable risk factors for vascular dementia (VaD), and recent research has proposed its association with AD. The field is considered unexplored when it comes to LBD, a prevalent form of alpha-synucleinopathies (AS). A second aim was to investigate cardiac disease and the presence of epicardial nerve alpha-synuclein (α-syn) as well as the cause of death in individuals with AS. In summary, the objective was to investigate and assemble broad clinicopathological data on CaVD, HT, and T2DM in AD and AS as well as to confirm the presence of cardiac α-syn and to determine the cause of death in AS. All studies were based on subjects who had undergone a thorough neuropathological examination of the brain. Pathological and clinical data were assembled through autopsy reports and medical records. A majority of the research in this field has not included neuropathological verification of the neurocognitive disorder (NCD).In Papers I and II, we investigated the prevalence of CaVD, found morphologically at autopsy, as well as clinical HT and T2DM in AD, VaD, mixed AD-VaD, and LBD. We found a low prevalence and no differences regarding CaVD between AD and LBD. This differed statistically from VaD in almost all parameters, which presented with a high prevalence of the studied parameters. The same differences were seen regarding HT and T2DM – a low prevalence in AD and LBD compared to a significantly higher prevalence in VaD.In Paper III, we investigated the presence of cardiac α-syn in AS patients and a control group with other (non-AS) NCDs. We found α-syn in almost all cases of AS (82%) and within different stages of the disease. No cases within the control group had cardiac nerves positive for α-syn. The samples negative to α-syn in the AS group did not cover the epicardium with stainable nerves. We judged it probable that all AS have α-syn in their cardiac nerves. In Paper IV, we investigated the immediate cause of death in AS individuals, postive for α-syn in their cardiac nerves compared to o control group with other (non-AS) NCDs. In addition, we assembled comprehensive data on pathological and clinical CaVD, HT, and T2DM. The majority of deaths within the AS group were interpreted as sudden cardiac death (SCD, 51.3%). These were judged to be of cardiac but not vascular-ischemic etiology. The prevalence of SCDs differed statistically from the control group where it was the second most common cause of death (22.6%, p < 0.001). No other differences were seen between the groups regarding clinicopathologial CaVD, HT, and T2DM. We have demonstrated that CaVD, HT, and T2DM have a low prevalence in the neurodegenerative disorders AD and LBD. Our findings oppose the claims of a causal association between these disorders. Furthermore, our results support the association of these risk factors with VaD. We have additionally indicated that α-syn is present in probably all cases of AS and within all stages of the disease. The high prevalence of SCD in AS indicate that the protein depositions may play a role for impaired cardiac function in these individuals.
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| 6. |
- Javanshiri, Keivan, et al.
(författare)
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Cardiovascular Disease, Diabetes Mellitus, and Hypertension in Lewy Body Disease: A Comparison with Other Dementia Disorders
- 2019
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Ingår i: Journal of Alzheimer's disease : JAD. - 1387-2877. ; 71:3, s. 851-859
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Tidskriftsartikel (refereegranskat)abstract
- Background: Research concerning the potential roles of cardiovascular disease (CaVD) and diabetes mellitus (DM) as risk factors for Lewy body disease (LBD) is limited. These disorders are, however, established risk factors for vascular dementia (VaD) and have been proposed as risk factors for Alzheimer’s disease (AD). Objective: The aim of this study was to investigate the prevalence of CaVD and DM in LBD and compare the results with previous findings in cases with AD, VaD, and mixed AD-VaD (MD). Methods: Autopsy reports at the Clinical Department of Pathology in Lund from 2001–2018 were analyzed. All cases with a complete neuropathological diagnosis of LBD were selected, not distinguishing between subjects with clinical Parkinson disease dementia and dementia with Lewy bodies, on the condition of a clinical diagnosis of dementia. Clinical data were retrieved through the patients’ medical records and the Swedish National Diabetes Register (NDR) and compared with those of the AD, VaD, and MD cases. Results: In LBD, there was less CaVD, significantly less DM (p = 0.002) and likewise significantly less hypertension (p < 0.001) than in VaD. The results of the LBD group were consistent with the results of the AD group. Conclusion Our findings of a low prevalence of CaVD and CaVD risk factors in LBD and in AD argue against the association between these risk factors and their contribution to the development of neurodegenerative diseases.
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| 7. |
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| 8. |
- Javanshiri, Keivan, et al.
(författare)
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Kardiovaskulär sjukdom och diabetes typ II som riskfaktorer för kognitiv sjukdom
- 2020
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Ingår i: Neurologi i Sverige. - 2000-8538. ; 1:2020, s. 52-55
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Here we presented a review of our two articles presenting the prevalence of cardiovascular disease and diabetes in neurocognitive disorders; Alzheimer's disease, vascular dementia, mixed dementa and Lewy body disease. Cardiovascular disease and diabetes showed a significantly lower prevalence among cases with Alzheimer's disease and Lewy body disease, both neurodegenerative disorders, compared to cases with vascular dementia. These findings strongly argue against the suggestions of Alzheimer's disease and vascular dementia sharing risk factors. All neurocognitive disorders where confirmed through neuropathological examination.
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| 9. |
- Javanshiri, Keivan, et al.
(författare)
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Sudden cardiac death in synucleinopathies
- 2023
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Ingår i: Journal of Neuropathology and Experimental Neurology. - : Oxford University Press (OUP). - 1554-6578 .- 0022-3069. ; 82:3, s. 242-249
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to investigate the cause of death in subjects with α-synucleinopathies (ASs) and the confirmed presence of cardiac α-synuclein (α-syn), compared to non-AS disorders in a neuropathologically confirmed cohort. In total, 78 neuropathologically confirmed AS cases positive for cardiac α-syn were included in the study. Individuals with other neurocognitive diseases, having no α-syn in the brainstem or above, nor in cardiac nerves, served as controls (n = 53). Data regarding the cause of death, cardiac α-syn, pathological cardiac findings, and cardio- and cerebrovascular disease were assembled from autopsy reports and medical records. In the AS group, there was a significantly higher prevalence of sudden cardiac death ([SCD]; n = 40, 51.3%) compared to the control group (n = 12, 22.6%, p
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| 10. |
- Matti, Nathalie, et al.
(författare)
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Locus Coeruleus Degeneration Differs Between Frontotemporal Lobar Degeneration Subtypes
- 2022
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877. ; 89:2, s. 463-471
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Tidskriftsartikel (refereegranskat)abstract
- Background: There are few studies on the locus coeruleus (LC) in frontotemporal lobar degeneration (FTLD) and the potential differences in the LC related to the underlying proteinopathy. Objective: The aim of this study was to investigate the LC in FTLD subgroups. Methods: Neuropathological cases diagnosed with FTLD were included. The subgroups consisted of FTLD with tau, transactive response DNA-binding protein 43 (TDP) and fused in sarcoma (FUS). Micro-and macroscopical degeneration of the LC were assessed with respect to the number of neurons and the degree of depigmentation. A group of cognitively healthy subjects and a group with vascular cognitive impairment (VCI) served as comparison groups. Results: A total of 85 FTLD cases were included, of which 44 had FTLD-TDP, 38 had FTLD-tau, and three had FTLD-FUS. The groups were compared with 25 VCI cases and 41 cognitively healthy control cases (N = 151 for the entire study). All FTLD groups had a statistically higher microscopical degeneration of the LC compared to the controls, but the FTLD-tau group had greater micro-and macroscopical degeneration than the FTLD-TDP group. Age correlated positively with the LC score in the FTLD-tau group, but not in the FTLD-TDP group. Conclusion: A greater microscopical degeneration of the LC was observed in all FTLD cases compared to healthy controls and those with VCI. The LC degeneration was more severe in FTLD-tau than in FTLD-TDP. The macroscopically differential degeneration of the LC in FTLD subgroups may facilitate differential diagnostics, potentially with imaging.
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