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1.
  • Zupanic, Eva, et al. (author)
  • Acute Stroke Care in Dementia : A Cohort Study from the Swedish Dementia and Stroke Registries
  • 2018
  • In: Journal of Alzheimer's Disease. - Amsterdam : IOS Press. - 1387-2877 .- 1875-8908. ; 66:1, s. 185-194
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Previous studies have shown that patients with dementia receive less testing and treatment for stroke.OBJECTIVES: Our aim was to investigate hospital management of acute ischemic stroke in patients with and without dementia.METHODS: Retrospective analysis of prospectively collected data 2010-2014 from the Swedish national dementia registry (SveDem) and the Swedish national stroke registry (Riksstroke). Patients with dementia who suffered an acute ischemic stroke (AIS) (n = 1,356) were compared with matched non-dementia AIS patients (n = 6,755). Outcomes included length of stay in a stroke unit, total length of hospitalization, and utilization of diagnostic tests and assessments.RESULTS: The median age at stroke onset was 83 years. While patients with dementia were equally likely to be directly admitted to a stroke unit as their non-dementia counterparts, their stroke unit and total hospitalization length were shorter (10.5 versus 11.2 days and 11.6 versus 13.5, respectively, p < 0.001). Dementia patients were less likely to receive carotid ultrasound (OR 0.36, 95% CI [0.30-0.42]) or undergo assessments by the interdisciplinary team members (physiotherapists, speech therapists, occupational therapists; p < 0.05 for all adjusted models). However, a similar proportion of patients received CT imaging (97.4% versus 98.6%, p = 0.001) and a swallowing assessment (90.7% versus 91.8%, p = 0.218).CONCLUSIONS: Patients with dementia who suffer an ischemic stroke have equal access to direct stroke unit care compared to non-dementia patients; however, on average, their stay in a stroke unit and total hospitalization are shorter. Dementia patients are also less likely to receive specific diagnostic tests and assessments by the interdisciplinary stroke team.
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2.
  • Mattsson, Niklas, 1979, et al. (author)
  • CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment.
  • 2009
  • In: JAMA : the journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 302:4, s. 385-93
  • Journal article (peer-reviewed)abstract
    • CONTEXT: Small single-center studies have shown that cerebrospinal fluid (CSF) biomarkers may be useful to identify incipient Alzheimer disease (AD) in patients with mild cognitive impairment (MCI), but large-scale multicenter studies have not been conducted. OBJECTIVE: To determine the diagnostic accuracy of CSF beta-amyloid(1-42) (Abeta42), total tau protein (T-tau), and tau phosphorylated at position threonine 181 (P-tau) for predicting incipient AD in patients with MCI. DESIGN, SETTING, AND PARTICIPANTS: The study had 2 parts: a cross-sectional study involving patients with AD and controls to identify cut points, followed by a prospective cohort study involving patients with MCI, conducted 1990-2007. A total of 750 individuals with MCI, 529 with AD, and 304 controls were recruited by 12 centers in Europe and the United States. Individuals with MCI were followed up for at least 2 years or until symptoms had progressed to clinical dementia. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative likelihood ratios (LRs) of CSF Abeta42, T-tau, and P-tau for identifying incipient AD. RESULTS: During follow-up, 271 participants with MCI were diagnosed with AD and 59 with other dementias. The Abeta42 assay in particular had considerable intersite variability. Patients who developed AD had lower median Abeta42 (356; range, 96-1075 ng/L) and higher P-tau (81; range, 15-183 ng/L) and T-tau (582; range, 83-2174 ng/L) levels than MCI patients who did not develop AD during follow-up (579; range, 121-1420 ng/L for Abeta42; 53; range, 15-163 ng/L for P-tau; and 294; range, 31-2483 ng/L for T-tau, P < .001). The area under the receiver operating characteristic curve was 0.78 (95% confidence interval [CI], 0.75-0.82) for Abeta42, 0.76 (95% CI, 0.72-0.80) for P-tau, and 0.79 (95% CI, 0.76-0.83) for T-tau. Cut-offs with sensitivity set to 85% were defined in the AD and control groups and tested in the MCI group, where the combination of Abeta42/P-tau ratio and T-tau identified incipient AD with a sensitivity of 83% (95% CI, 78%-88%), specificity 72% (95% CI, 68%-76%), positive LR, 3.0 (95% CI, 2.5-3.4), and negative LR, 0.24 (95% CI, 0.21-0.28). The positive predictive value was 62% and the negative predictive value was 88%. CONCLUSIONS: This multicenter study found that CSF Abeta42, T-tau, and P-tau identify incipient AD with good accuracy, but less accurately than reported from single-center studies. Intersite assay variability highlights a need for standardization of analytical techniques and clinical procedures.
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3.
  • Hooshmand, Babak, et al. (author)
  • Associations between serum homocysteine, holotranscobalamin, folate and cognition in the elderly : a longitudinal study
  • 2012
  • In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 271:2, s. 204-212
  • Journal article (peer-reviewed)abstract
    • Objectives:  To examine the associations of serum homocysteine (tHcy), Holotranscobalamin (holoTC), the biologically active fraction of vitamin B12, and folate with cognitive functioning in a longitudinal population-based study of Finnish elderly. Subjects and design:  tHcy, holoTC, and folate were measured at baseline in 274 dementia-free subjects aged 65-79 years derived from the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study. Subjects were re-investigated 7 years later and global cognition, episodic memory, executive functioning, verbal expression, and psychomotor speed were assessed. Results:  Higher baseline tHcy values were associated with poorer performance on global cognition: relative difference (95% confidence interval) was: 0.90 (0.81 - 0.99); episodic memory: 0.87 (0.77 - 0.99); executive functions: 0.86 (0.75 - 0.98), and verbal expression: 0.89 (0.81 - 0.97) at follow-up. Increased holoTC levels were related to better performance on global cognition: 1.09 (1.00 - 1.19), executive functions: 1.11 (1.01 - 1.21), and psychomotor speed: 1.13 (1.01 - 1.26). After excluding 20 incident dementia cases, increased tHcy remained associated with poorer performance in episodic memory, execution functions, and verbal expression. Higher holoTC values tended to relate to better performance in executive functions and psychomotor speed while elevated serum folate concentrations were significantly related to higher scores in global cognition and verbal expression tests. Conclusions:  tHcy, holoTC, and folate measured 7 years earlier are related to cognitive performance even in non-demented elderly. Randomized trials are needed to determine the impact of vitamin B12 and folate supplementations on preventing cognitive decline in the elderly.
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4.
  • Håkansson, Krister, 1952-, et al. (author)
  • Association between mid-life marital status and cognitive function in later life : population based cohort study
  • 2009
  • In: The BMJ. - : BMJ. - 1756-1833 .- 0959-8138 .- 1468-5833. ; 339:July, s. Article number: b2462-
  • Journal article (peer-reviewed)abstract
    • Objectives To evaluate whether mid-life marital status is related to cognitive function in later life. Design Prospective population based study with an average follow-up of 21 years. Setting Kuopio and Joensuu regions in eastern Finland. Participants Participants were derived from random, population based samples previously investigated in 1972, 1977, 1982, or 1987; 1449 individuals (73%), aged 65-79, underwent re-examination in 1998. Main outcome measures Alzheimer's disease and mild cognitive impairment. Results People cohabiting with a partner in mid-life (mean age 50.4) were less likely than all other categories (single, separated, or widowed) to show cognitive impairment later in life at ages 65-79. Those widowed or divorced in mid-life and still so at follow-up had three times the risk compared with married or cohabiting people. Those widowed both at mid-life and later life had an odds ratio of 7.67 (1.6 to 40.0) for Alzheimer's disease compared with married or cohabiting people. The highest increased risk for Alzheimer's disease was in carriers of the apolipoprotein E e4 allele who lost their partner before mid-life and were still widowed or divorced at follow-up. The progressive entering of several adjustment variables from mid-life did not alter these associations. Conclusions Living in a relationship with a partner might imply cognitive and social challenges that have a protective effect against cognitive impairment later in life, consistent with the brain reserve hypothesis. The specific increased risk for widowed and divorced people compared with single people indicates that other factors are needed to explain parts of the results. A sociogenetic disease model might explain the dramatic increase in risk of Alzheimer's disease for widowed apolipoprotein E e4 carriers.
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5.
  • Enache, Daniela, et al. (author)
  • CAIDE Dementia Risk Score and biomarkers of neurodegeneration in memory clinic patients without dementia
  • 2016
  • In: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 42, s. 124-131
  • Journal article (peer-reviewed)abstract
    • The aim of this study was to explore cross-sectional associations between Cardiovascular Risk Factors, Aging and Dementia Study (CAIDE) Dementia Risk Score and dementia-related cerebrospinal fluid and neuroimaging biomarkers in 724 patients without dementia from the Memory Clinic at Karolinska University Hospital, Huddinge, Sweden. We additionally evaluated the score's capacity to predict dementia. Two risk score versions were calculated: one including age, gender, obesity, hyperlipidemia, and hypertension; and one additionally including apolipoprotein E (APOE) ε4 carrier status. Cerebrospinal fluid was analyzed for amyloid β (Aβ), total tau, and phosphorylated tau. Visual assessments of medial temporal lobe atrophy (MTA), global cortical atrophy-frontal subscale, and Fazekas scale for white matter changes (WMC) were performed. Higher CAIDE Dementia Risk Score (version without APOE) was significantly associated with higher total tau, more severe MTA, WMC, and global cortical atrophy-frontal subscale. Higher CAIDE Dementia Risk Score (version with APOE) was associated with reduced Aβ, more severe MTA, and WMC. CAIDE Dementia Risk Score version with APOE seemed to predict dementia better in this memory clinic population with short follow-up than the version without APOE.
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6.
  • Xu, Wei-Li, et al. (author)
  • Accelerated Progression from Mild Cognitive Impairment to Dementia Among APOE epsilon 4 epsilon 4 Carriers
  • 2013
  • In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 33:2, s. 507-515
  • Journal article (peer-reviewed)abstract
    • The impact of APOE ε4 on mild cognitive impairment (MCI) and its progression to dementia remain controversial. We aimed to examine the association of APOE ε4 with MCI, and to verify the hypothesis that ε4 accelerates progression from MCI to dementia. In the Kungsholmen project, 756 cognitively healthy participants and 212 people with MCI aged ≥75 years were identified at baseline. Amnestic MCI (aMCI) and other cognitive impairment no dementia (oCIND) as two subtypes of MCI were assessed based on standard definitions. The two cohorts were followed for 9 years to detect incident cases of MCI and dementia following international criteria. APOE genotypes were assessed at baseline. Data were analyzed using Cox models. During the follow-up, in the cognitively healthy cohort, 165 people developed MCI (40 aMCI and 125 oCIND) and 176 developed dementia; in the MCI cohort, 118 persons progressed to dementia. Compared with APOE ε3ε3, the hazard ratios (HRs) (95% CIs) of ε2ε4/ε3ε4 were 2.24 (1.10-4.57) for aMCI and 1.78 (1.15-2.75) for oCIND, while the ε4ε4 was related to dementia with a HR of 4.35 (1.97-9.63) in the cognitively healthy cohort. In the MCI cohort, the ε4ε4 genotype led to a multi-adjusted HR of 2.89 (1.12-7.48) for dementia and accelerated the progression to dementia by 3.36 years. The APOE ε4 heterozygotes are associated with an increased risk of aMCI and oCIND. The ε4 homozygote substantially accelerates progression from MCI to dementia, and anticipate dementia occurrence by more than 3 years in people with MCI.
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7.
  • Kramberger, Milica Gregoric, et al. (author)
  • Cerebrospinal fluid alzheimer markers in depressed elderly dubjects with and without alzheimer's disease
  • 2012
  • In: Dementia and Geriatric Cognitive Disorders Extra. - : S. Karger AG. - 1664-5464. ; 2:1, s. 48-56
  • Journal article (peer-reviewed)abstract
    • Background: The aim of this study was to explore the relationship between cerebrospinal fluid Alzheimer's disease (AD) markers and depression in elderly people.Method: We included subjects with AD as well as persons with subjective cognitive impairment and normal cognition. Depression was assessed with the Cornell Scale for Depression in Dementia, and a cut-off score of >6 was used to define depression. Cerebrospinal fluid was analyzed using commercially available assays for β-amyloid 1-42, total tau, and phosphorylated tau 181.Result: A total of 183 participants (66.7% female) were included (92 with AD and 91 with subjective cognitive impairment), with a mean age (±SD) of 67.6 ± 7.4 years, a Mini-Mental State Examination score of 26.0 ± 4.0, and a median Cornell Scale for Depression in Dementia score of 5 (range 0-19). Depression scores were not associated with higher phosphorylated tau 181 and total tau or reduced β-amyloid 1-42 in AD or non-demented subjects.Conclusions: These results suggest that AD pathology does not contribute to depression, indicating that other factors may be more important. Further studies of the aetiology of depression in elderly people with and without AD are warranted.
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8.
  • Qiu, Chengxuan, et al. (author)
  • Twenty-year changes in dementia occurrence suggest decreasing incidence in central Stockholm, Sweden
  • 2013
  • In: Neurology. - 0028-3878 .- 1526-632X. ; 80:20, s. 1888-1894
  • Journal article (peer-reviewed)abstract
    • Objective: To explore whether prevalence, survival, and incidence of dementia have changed from 1987–1994 to 2001–2008 in Stockholm, Sweden.Methods: This study is based on 2 cross-sectional surveys of people aged 75 years or over conducted in central Stockholm: the Kungsholmen Project (KP) (1987–1989, n = 1,700) and the Swedish National study on Aging and Care in Kungsholmen (SNAC-K) (2001–2004, n = 1,575). In both surveys we diagnosed dementia according to DSM-III-R criteria, following the identical diagnostic procedure. Death certificates were used to determine survival status of KP participants as of December 1994 and SNAC-K participants as of June 2008. We used logistic and Cox models to compare prevalence and survival, controlling for major confounders. We inferred incidence of dementia according to its relationship with prevalence and survival.Results: At baseline, 225 subjects in KP and 298 in SNAC-K were diagnosed with dementia. The age- and sex-standardized prevalence of dementia was 17.5% (12.8% in men; 19.2% in women) in KP and 17.9% (10.8% in men; 20.5% in women) in SNAC-K. The adjusted odds ratio of dementia in SNAC-K vs KP was 1.17 (95% confidence interval 0.95–1.46). The multiadjusted hazard ratio of death in SNAC-K vs KP was 0.71 (0.57–0.88) in subjects with dementia, 0.68 (0.59–0.79) in those without dementia, and 0.66 (0.59–0.74) in all participants.Conclusions: Prevalence of dementia was stable from the late 1980s to the early 2000s in central Stockholm, Sweden, whereas survival of patients with dementia increased. These results suggest that incidence of dementia may have decreased during this period.
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9.
  • Järemo, Petter, et al. (author)
  • Alzheimer's disease and granulocyte density diversity
  • 2013
  • In: European Journal of Clinical Investigation. - : John Wiley & Sons. - 0014-2972 .- 1365-2362. ; 43:6, s. 545-548
  • Journal article (peer-reviewed)abstract
    • BACKGROUND:The current study investigates circulating eosinophils and neutrophils in Alzheimer's (AD) type dementia with respect to density (kg/L). The existence of β-amyloid plaques in the brain is a feature of AD. Sporadic scientific reports indicate that the disease affects circulating neutrophils. In contrast, numerous publications investigate inflammatory reactions in AD brains. Locally, the plaques evoke a substantial inflammatory response involving activated microglia and astrocytes.METHODS:Subjects with probable AD (n = 39) were included and compared with elderly individuals (n = 22) lacking apparent memory problems. We sampled 10 mL venous blood in citrate. Granulocytes were separated according to density in linear Percoll™ gradients. Subsequently, the gradients were divided into density subfractions (n = 16). In every fraction, determination of eosinophil and neutrophil counts was carried out.RESULTS:AD sufferers displayed less granulocytes in fractions nos. 13-15 containing light cells. For these fractions, the P-values proved to be (P < 0·001; not significant; P = 0·03) and (P = 0·01; P = 0·01; not significant), for eosinophils and neutrophils, respectively.CONCLUSIONS:The present work describes that less circulating light granulocytes are a feature of AD demented individuals. It is to hypothesize that it is a sign of impaired granulocyte turnover and cell damage. It is concluded that AD affects inflammatory cells in the periphery and that the behaviour of granulocytes in dementia is worthwhile further studies.
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10.
  • Subic, Ana, et al. (author)
  • Treatment of Atrial Fibrillation in Patients with Dementia : A Cohort Study from the Swedish Dementia Registry
  • 2018
  • In: Journal of Alzheimer's Disease. - Amsterdam, Netherlands : IOS Press. - 1387-2877 .- 1875-8908. ; 61:3, s. 1119-1128
  • Journal article (peer-reviewed)abstract
    • Background: Patients with dementia might have higher risk for hemorrhagic complications with anticoagulant therapy prescribed for atrial fibrillation (AF).Objective: This study assesses the risks and benefits of warfarin, antiplatelets, and no treatment in patients with dementia and AF.Methods: Of 49,792 patients registered in the Swedish Dementia Registry 2007-2014, 8,096 (16%) had a previous diagnosis of AF. Cox proportional hazards models were used to calculate the risk for ischemic stroke (IS), nontraumatic intracranial hemorrhage, any-cause hemorrhage, and death.Results: Out of the 8,096 dementia patients with AF, 2,143 (26%) received warfarin treatment, 2,975 (37%) antiplatelet treatment, and 2,978 (37%) had no antithrombotic treatment at the time of dementia diagnosis. Patients on warfarin had fewer IS than those without treatment (5.2% versus 8.7%; p < 0.001) with no differences compared to antiplatelets. In adjusted analyses, warfarin was associated with a lower risk for IS (HR 0.76, CI 0.59-0.98), while antiplatelets were associated with increased risk (HR 1.25, CI 1.01-1.54) compared to no treatment. For any-cause hemorrhage, there was a higher risk with warfarin (HR 1.28, CI 1.03-1.59) compared to antiplatelets. Warfarin and antiplatelets were associated with a lower risk for death compared to no treatment.Conclusions: Warfarin treatment in Swedish patients with dementia is associated with lower risk of IS and mortality, and a small increase in any-cause hemorrhage. This study supports the use of warfarin in appropriate cases in patients with dementia. The low percentage of patients on warfarin treatment indicates that further gains in stroke prevention are possible.
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