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4.
  • Olofsson, Jonas K, 1965-, et al. (författare)
  • Odor identification impairment in carriers of ApoE-ε4 is independent of clinical dementia
  • 2010
  • Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 31:4, s. 567-577
  • Tidskriftsartikel (refereegranskat)abstract
    • The ApoE gene is expressed in olfactory brain structures and is believed to play a role in neuronal regenerative processes as well as in development of Alzheimer's disease (AD), the most common form of dementia. The ε4 allele has been reported to be associated with compromised odor identification ability in the elderly, and this deficit has been interpreted as a sign of pre-diagnostic AD. However, because it has not been demonstrated that the relationship between the ε4 allele and odor identification is mediated by dementia, it is possible that the ε4 allele may have an effect on odor identification over and above any effects of dementia. The present study investigated effects of ApoE-status on odor identification in a large, population-based sample (n = 1236) of adults (45–80 years), who were assessed for dementia at time of testing and 5 years later. The results showed that the ε4 allele was associated with an odor identification deficit among elderly participants (75–80). Critically, this effect remained after current and pre-diagnostic dementia, vocabulary, global cognitive status and health variables were partialled out. The present results suggest that the ApoE gene plays a role in olfactory functioning that is independent of dementia conversion within 5 years.
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5.
  • Allard, Per, et al. (författare)
  • Age-correlated loss of dopamine uptake sites labeled with [3H]GBR-12935 in human putamen.
  • 1989
  • Ingår i: Neurobiology of Aging. - 0197-4580 .- 1558-1497. ; 10:6, s. 661-4
  • Tidskriftsartikel (refereegranskat)abstract
    • The effects of age (19-100 years) upon dopamine uptake sites labeled with [3H]GBR-12935 in human postmortem putamen from 20 individuals were studied. There was a 70% decrease in binding density (Bmax) over the adult age range. No significant changes in binding affinity (Kd) were detected, the mean Kd being 1.0 +/- 0.2 nM (mean +/- S.E.M.). Nor were there any changes in binding related to the postmortem delay. Based on the findings that [3H]GBR-12935 labels the uptake site for dopamine, it is suggested that the age-related loss of [3H]GBR-12935 binding in human putamen reflects a degeneration of dopamine neurites.
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6.
  • Almkvist, Ove, et al. (författare)
  • Longitudinal cognitive decline in autosomal-dominant Alzheimer's disease varies with mutations in APP and PSEN1 genes
  • 2019
  • Ingår i: ; 82, s. 40-47
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose was to compare longitudinal cognitive changes in APP and PSEN1 gene mutation carriers and noncarriers from four autosomal-dominant Alzheimer's disease (ADAD) families across preclinical and early clinical stages of disease. Carriers (n = 34) with four different mutations (PSEN1(M146V), PSEN1(H163Y), APP(SWE), and APP(ARC)) and noncarriers (n = 41) were followed up longitudinally with repeated cognitive assessments starting many years before the expected clinical onset. The relationship between cognition and years to expected clinical onset, education, age, and type of mutation was analyzed using mixed-effects models. Results showed an education-dependent and time-related cognitive decline with linear and quadratic predictors in mutation carriers. Cognitive decline began close to the expected clinical onset and was relatively rapid afterward in PSEN1 mutation carriers, whereas decline was slower and started earlier than 10 years before expected clinical onset in APP mutation carriers. In noncarriers, the decline was minimal across time in accordance with normal aging. These results suggest that phenotypes for onset and rate of cognitive decline vary with PSEN1 and APP genes, suggesting a behavioral heterogeneity in ADAD. (C) 2019 Elsevier Inc. All rights reserved.
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7.
  • Andersson, A, et al. (författare)
  • Platelet [3H]paroxetine binding to 5-HT uptake sites in Alzheimer's disease.
  • 1991
  • Ingår i: Neurobiology of Aging. - 0197-4580 .- 1558-1497. ; 12:5, s. 531-4
  • Tidskriftsartikel (refereegranskat)abstract
    • Platelet serotonin (5-hydroxytryptamine, 5-HT) uptake sites were studied in a control group (n = 30) and an Alzheimer group (n = 40) using [3H]paroxetine as radioligand. The maximum number of binding sites (Bmax) for control (1250 +/- 60 fmol/mg protein) was not different from the Alzheimer group (1280 +/- 40 fmol/mg protein). There were no differences in apparent binding affinity (Kd): 0.046 (0.024-0.062) nM for control and 0.040 (0.027-0.061) nM for Alzheimer. Thus even though several previous studies have demonstrated marked atrophy of 5-HT containing neurites and 5-HT uptake sites in Alzheimer's disease, these findings are not found in the periphery on platelets. The platelet 5-HT uptake site cannot be used as a peripheral marker of Alzheimer's disease.
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8.
  • Andersson, Christin, et al. (författare)
  • Increasing CSF phospho-tau levels during cognitive decline and progression to dementia
  • 2008
  • Ingår i: Neurobiology of Aging. - 0197-4580 .- 1558-1497. ; 29:10, s. 1466-1473
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Little is known about longitudinal changes of cerebrospinal fluid (CSF) biomarkers during cognitive decline in neurodegenerative disease progression. Objective To investigate longitudinal changes in CSF biomarkers – total-tau (T-tau), phospho-tau (P-tau) and β-amyloid (Aβ42) – during cognitive decline. Methods Forty memory clinic patients (47.5% females), aged 61.3 ± 7.6 (S.D.) years, non-demented at baseline, underwent lumbar puncture and neuropsychological testing at two occasions. Baseline mean MMSE-score was 28.3 ± 1.8. Patients were divided into three groups based on baseline memory functioning; severely impaired (SIM), moderately impaired (MIM) and no impairment (NIM). Results There was a significant increase in P-tau in the SIM-group during follow-up, while P-tau in MIM and NIM did not change. Eighty-three percent of the SIM-patients converted to dementia (80% AD), while most MIM- and NIM-patients remained non-demented. T-tau- and Aβ42-levels did not change in any of the memory groups during follow-up. Conclusion Increasing P-tau levels during cognitive decline and conversion to dementia suggest that P-tau may be useful as a longitudinal marker of the neurodegenerative process.
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9.
  • Ashton, Nicholas J., et al. (författare)
  • No association of salivary total tau concentration with Alzheimer's disease.
  • 2018
  • Ingår i: Neurobiology of aging. - : Elsevier. - 1558-1497 .- 0197-4580. ; 70, s. 125-127
  • Tidskriftsartikel (refereegranskat)abstract
    • There is a need for an accessible biomarker that can complement current cerebrospinal fluid and imaging biomarkers in an accurate and early diagnosis of Alzheimer disease (AD). Saliva is a rich source of potential biomarkers and proteins related to neurodegenerative disorders have been shown to be present in this matrix, including tau. In this study, we quantified salivary total tau (t-tau) concentration in 160 healthy elderly control, 68 mild cognitive impairment, and 53 AD participants using ultrasensitive Single molecule array (Simoa) technology. No median difference in salivary t-tau concentration was found between AD and mild cognitive impairment or healthy elderly control (12.3 ng/L, 9.8 ng/L and 9.6 ng/L, respectively, p = 0.219). In addition, there was no association of salivary t-tau concentration with neurophysiological assessment or structural magnetic resonance imaging. Despite a nominal increase in AD, due to the large overlaps in concentrations between clinical groups, we conclude that salivary t-tau is a suitable biomarker neither for AD nor for cognitive impairment.
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10.
  • Benedict, Christian, et al. (författare)
  • Association between physical activity and brain health in older adults
  • 2013
  • Ingår i: Neurobiology of Aging. - 0197-4580 .- 1558-1497. ; 34:1, s. 83-90
  • Tidskriftsartikel (refereegranskat)abstract
    • In the present cross-sectional study, we examined physical activity (PA) and its possible association with cognitive skills and brain structure in 331 cognitively healthy elderly. Based on the number of self-reported light and hard activities for at least 30 minutes per week, participants were assigned to 4 groups representing different levels of PA. The cognitive skills were assessed by the Mini Mental State Examination score, a verbal fluency task, and the Trail-making test as a measure of visuospatial orientation ability. Participants also underwent a magnetic resonance imaging of the brain. Multiple regression analysis revealed that greater PA was associated with a shorter time to complete the Trail-making test, and higher levels of verbal fluency. Further, the level of self-reported PA was positively correlated with brain volume, white matter, as well as a parietal lobe gray matter volume, situated bilaterally at the precuneus. These present cross-sectional results indicate that PA is a lifestyle factor that is linked to brain structure and function in late life.
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