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Sökning: WFRF:(Londos Elisabet)

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31.
  • Guerreiro, R., et al. (författare)
  • Investigating the genetic architecture of dementia with Lewy bodies: a two-stage genome-wide association study
  • 2018
  • Ingår i: Lancet Neurology. - 1474-4422. ; 17:1, s. 64-74
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Dementia with Lewy bodies is the second most common form of dementia in elderly people but has been overshadowed in the research field, partly because of similarities between dementia with Lewy bodies, Parkinson's disease, and Alzheimer's disease. So far, to our knowledge, no large-scale genetic study of dementia with Lewy bodies has been done. To better understand the genetic basis of dementia with Lewy bodies, we have done a genome-wide association study with the aim of identifying genetic risk factors for this disorder. Methods In this two-stage genome-wide association study, we collected samples from white participants of European ancestry who had been diagnosed with dementia with Lewy bodies according to established clinical or pathological criteria. In the discovery stage (with the case cohort recruited from 22 centres in ten countries and the controls derived from two publicly available database of Genotypes and Phenotypes studies [phs000404.v1.p1 and phs000982.v1.p1] in the USA), we performed genotyping and exploited the recently established Haplotype Reference Consortium panel as the basis for imputation. Pathological samples were ascertained following autopsy in each individual brain bank, whereas clinical samples were collected after participant examination. There was no specific timeframe for collection of samples. We did association analyses in all participants with dementia with Lewy bodies, and also only in participants with pathological diagnosis. In the replication stage, we performed genotyping of significant and suggestive results from the discovery stage. Lastly, we did a meta-analysis of both stages under a fixed-effects model and used logistic regression to test for association in each stage. Findings This study included 1743 patients with dementia with Lewy bodies (1324 with pathological diagnosis) and 4454 controls (1216 patients with dementia with Lewy bodies vs 3791 controls in the discovery stage; 527 vs 663 in the replication stage). Results confirm previously reported associations: APOE (rs429358; odds ratio [OR] 2.40, 95% CI 2.14-2.70; p=1.05 x 10-48), SNCA (rs7681440; OR 0.73, 0.66-0.81; p=6.39 x 10(-10)), and GBA (rs35749011; OR 2.55, 1.88-3.46; p=1.78 x 10(-9)). They also provide some evidence for a novel candidate locus, namely CNTN1 (rs7314908; OR 1.51, 1.27-1.79; p=2.32 x 10(-6)); further replication will be important. Additionally, we estimate the heritable component of dementia with Lewy bodies to be about 36%. Interpretation Despite the small sample size for a genome-wide association study, and acknowledging the potential biases from ascertaining samples from multiple locations, we present the most comprehensive and well powered genetic study in dementia with Lewy bodies so far. These data show that common genetic variability has a role in the disease.
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32.
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33.
  • Hall, Sara, et al. (författare)
  • Plasma Phospho-Tau Identifies Alzheimer's Co-Pathology in Patients with Lewy Body Disease
  • 2021
  • Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 36:3, s. 767-771
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Alzheimer's disease co-pathology is common in dementia with Lewy bodies and Parkinson's disease with dementia (Lewy body disease) and can reliably be detected with positron emission tomography (PET) or cerebrospinal fluid (CSF) biomarkers. Recently developed blood biomarkers are more accessible and less expensive alternatives. Objective: To investigate if plasma phospho-tau217 and phospho-tau181 can detect Alzheimer's pathology in Lewy body disease with dementia. Methods: In this cross-sectional study we investigated plasma phospho-tau217 and phospho-tau181 in 35 patients with Lewy body disease with dementia. Patients underwent tau-PET imaging (18F-RO948). Results: Plasma phospho-tau217 correlated with plasma phospho-tau181, CSF phospho-tau217 (rs = 0.68, P < 0.001), and negatively with CSF β-amyloid42/40 (rs = −0.52, P = 0.001). Plasma phospho-tau217 and phospho-tau181 correlated with tau-PET signal in the temporal cortex (rs > 0.56, P < 0.001) and predicted abnormal tau-PET status and β-amyloid status (area under the curve > 0.78 and > 0.81, respectively). Conclusion: Plasma phospho-tau might be a useful marker for Alzheimer's co-pathology in Lewy body disease with dementia.
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34.
  • Hansen Kristensson, Jenny, et al. (författare)
  • Medications causing potential cognitive impairment are common in nursing home dementia units – A cross-sectional study
  • 2021
  • Ingår i: Exploratory Research in Clinical and Social Pharmacy. - : Elsevier BV. - 2667-2766. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundWith advancing age the brain becomes more sensitive to centrally acting drugs thus increasing the risk of cognitive side-effects. The Swedish National Board of Health and Welfare developed indicators to measure and follow quality in older people's drug therapy, one being “Potentially Inappropriate Medications risking Cognitive impairment (PIMcogn)”. Associations between anticholinergics and cognitive impairment are described, especially in persons with Alzheimer's disease or Lewy Body Dementia/Parkinson's disease dementia, due to degenerated cholinergic pathways.ObjectivesTo examine the prevalence of PIMcogn and if it differed between nursing home residents with and without a dementia diagnosis and between residents with different dementia aetiologias.MethodsDescriptive cross-sectional study, based on residents ≥65 years in nursing home dementia units in Malmö, Sweden, in 2012–2013 (N = 574).ResultsThe study population consisted of 76% women, the mean age was 86 years and a dementia diagnosis was registered in 92%. A total of 74% were prescribed at least one PIMcogn. Benzodiazepines were prevalent in 59%, opioids in 27%, antipsychotics in 20% and anticholinergics in 13%. Opioids used regularly and antiepileptics were more common in residents without a dementia diagnosis. The lowest proportion of anticholinergics was seen in the oldest age group, 11.0%. There was no difference seen in anticholinergics between dementia types with considerable cholinergic deficit and other dementia diagnoses.ConclusionsTreatment with at least one PIMcogn was common. Usage of benzodiazepines and antipsychotics was, despite the knowledge of alarming side-effects, high.An awareness of the inappropriateness in prescribing anticholinergics to the oldest old seems to be apparent, but not to persons with cholinergic deficit.
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35.
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36.
  • Hansson, Oskar, et al. (författare)
  • Evaluation of plasma Abeta(40) and Abeta(42) as predictors of conversion to Alzheimer's disease in patients with mild cognitive impairment.
  • 2010
  • Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 31:3, s. 357-67
  • Tidskriftsartikel (refereegranskat)abstract
    • Numerous studies have shown a marked decrease of beta-amyloid(42) (Abeta(42)) in the cerebrospinal fluid (CSF) of patients with incipient Alzheimer's disease (AD). However, studies on Abeta in plasma are contradictory, and show very marginal differences between patients and controls. Here, we analyzed plasma samples using a new multiplex immunoassay for simultaneous analysis of Abeta(1-40), Abeta(n-40), Abeta(1-42), and Abeta(n-42). The plasma samples were obtained at baseline from two independent cohorts of patients with mild cognitive impairment (MCI) and age-matched controls. In the first cohort, 41% of the 117 MCI cases converted to AD during a clinical follow-up period of 4-7 years. In the second cohort, 14% of the 110 MCI subjects developed AD during a clinical follow-up period of 2-4 years. None of the plasma Abeta isoforms differed between MCI patients that subsequently developed AD and healthy controls or stable MCI patients. The Cox proportional hazards model did not reveal any differences in the probability of progression from MCI to AD related to plasma Abeta levels. In contrast, low levels of Abeta(1-42) in CSF were strongly associated with increased risk of future AD. The absence of a change in plasma Abeta in incipient AD, despite the marked change in CSF, may be explained by the lack of a correlation between the levels of Abeta(1-42) in CSF and plasma. In conclusion, the results show that CSF biomarkers are better predictors of progression to AD than plasma Abeta isoforms.
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37.
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38.
  • Hansson, Oskar, et al. (författare)
  • Prediction of Alzheimer's disease using the CSF A beta 42/A beta 40 ratio in patients with mild cognitive impairment
  • 2007
  • Ingår i: DEMENTIA AND GERIATRIC COGNITIVE DISORDERS. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 23:5, s. 316-320
  • Tidskriftsartikel (refereegranskat)abstract
    • Evidence supports an important role for β-amyloid (Aβ) in the pathogenesis of Alzheimer’s disease (AD). Here, we investigate baseline levels of the 40- and 42-amino-acid-long Aβ peptides (Aβ40 and Aβ42) in cerebrospinal fluid (CSF) from a cohort of patients with mild cognitive impairment (MCI, n = 137) in relation to the final diagnosis after 4–6 years of follow-up time. CSF Aβ42 concentration at baseline and the Aβ42/Aβ40 ratio were significantly decreased in the MCI patients who developed AD as compared to cognitively stable MCI patients and MCI patients who developed other forms of dementia (p < 0.001). The baseline levels of Aβ40 were similar in all MCI groups but correlated with change in Mini Mental State Examination scores in converters to AD. The Aβ42/Aβ40 ratio was superior to Aβ42 concentration with regard to identifying incipient AD in MCI (p < 0.05). In conclusion, the data provide further support for the view that amyloid precursor protein metabolism is disturbed in early sporadic AD and points to the usefulness of the Aβ42/Aβ40 ratio as a predictive biomarker for AD.
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39.
  • Heyman, Isak, et al. (författare)
  • Exploring the prevalence of undetected bradyarrhythmia in dementia with Lewy bodies
  • 2023
  • Ingår i: Clinical autonomic research : official journal of the Clinical Autonomic Research Society. - 1619-1560. ; 33:4, s. 433-442
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: To explore the prevalence of undetected bradyarrhythmia in a cohort of people with dementia with Lewy bodies.METHODS: Thirty participants diagnosed with dementia with Lewy bodies were enrolled from three memory clinics in southern Sweden between May 2021 and November 2022. None had a history of high-grade atrioventricular block or sick sinus syndrome. Each participant underwent orthostatic testing, cardiac [ 123I]metaiodobenzylguanidine scintigraphy and 24-h ambulatory electrocardiographic monitoring. Concluding bradyarrhythmia diagnosis was obtained until the end of December 2022. RESULTS: Thirteen participants (46.4%) had bradycardia at rest during orthostatic testing and four had an average heart rate < 60 beats per minute during ambulatory electrocardiographic monitoring. Three participants (10.7%) received a diagnosis of sick sinus syndrome, of whom two received pacemaker implants to manage associated symptoms. None received a diagnosis of second- or third-degree atrioventricular block.CONCLUSION: This report showed a high prevalence of sick sinus syndrome in a clinical cohort of people with dementia with Lewy bodies. Further research on the causes and consequences of sick sinus syndrome in dementia with Lewy bodies is thus warranted.
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40.
  • Heyman, Isak, et al. (författare)
  • Pacemaker Implants and Their Influence on the Daily Life of Patients with Dementia with Lewy Bodies : A Qualitative Case Study
  • 2023
  • Ingår i: Neurology and Therapy. - 2193-8253. ; 12:4, s. 1359-1373
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Dementia with Lewy bodies (DLB) is an incurable form of dementia associated with detriments to the daily life of patients and carers from their family. Symptoms of orthostatic hypotension, syncope, and falls are supportive of DLB diagnosis. These symptoms may also be present among people with sick sinus syndrome (SSS), and subsequent pacemaker treatment to manage bradyarrhythmia is associated with improved cognitive function. The prevalence of SSS seems to be higher among people with underlying Lewy body pathology compared to the general age-matched population (5.2% vs. 0.17%). To our knowledge, how people with DLB and their family carers may experience pacemaker treatment to manage bradyarrhythmia has not been previously reported. Therefore, the aim of this study was to explore how people with DLB experience daily life following a pacemaker implant to manage associated symptoms of bradyarrhythmia.METHODS: A qualitative case study design was used. Two men with DLB and their spouse carers were repeatedly interviewed as a dyad within 1 year following implant of a dual-chamber rate-adaptive (DDD-CLS) pacemaker to manage SSS in the men. Content analysis was used to assess the qualitative interview data collected.RESULTS: Three categories emerged: (1) gaining control, (2) maintaining a social life, and (3) being influenced by concurrent diseases. Less syncope/falls and remote pacemaker monitoring increased a sense of control in everyday life, while perceived physical and/or cognitive improvements influenced social participation. The men were still affected by concurrent diseases, which continuously influenced each couple's daily life.CONCLUSION: Identifying and managing concurrent bradyarrhythmia through a pacemaker implant could improve well-being for people with DLB.
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