| 11. |
- Bruno, Davide, et al.
(författare)
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Levels of cerebrospinal fluid neurofilament light protein in healthy elderly vary as a function of TOMM40 variants.
- 2012
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Ingår i: Experimental gerontology. - : Elsevier BV. - 1873-6815 .- 0531-5565. ; 47:5, s. 347-52
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Tidskriftsartikel (refereegranskat)abstract
- Neurofilament light (NFL) proteins in cerebrospinal fluid (CSF) are a marker of neuronal damage, especially subcortical axonal injury and white matter disease. Subjects with Alzheimer's disease (AD) have shown elevated levels of CSF NFL as compared to controls. However, the presence of the APOE ε4 allele, an established risk factor for AD, was not found to associate with higher CSF NFL concentrations. We examined whether TOMM40 variants, which have been reported to influence age of onset of AD and are in linkage disequilibrium with APOE, have an effect on CSF NFL levels, in 47 healthy, cognitively intact individuals with or without APOE ε4. Our results show that the presence of APOE ε4 alone does not affect CSF NFL levels significantly; however APOE and TOMM40 appear to interact. Subjects with APOE ε4 have higher CSF NFL levels than non-ε4 carriers, only when they do not carry a short poly-T variant of TOMM40, which is associated with later age of onset of AD, and may act as protective against the dose effect of ε4.
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| 12. |
- Buerger, Katharina, et al.
(författare)
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Validation of Alzheimer's disease CSF and plasma biological markers: the multicentre reliability study of the pilot European Alzheimer's Disease Neuroimaging Initiative (E-ADNI).
- 2009
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Ingår i: Experimental gerontology. - : Elsevier BV. - 1873-6815 .- 0531-5565. ; 44:9, s. 579-85
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Alzheimer's Disease Neuroimaging Initiatives ("ADNI") aim to validate neuroimaging and biochemical markers of Alzheimer's disease (AD). Data of the pilot European-ADNI (E-ADNI) biological marker programme of cerebrospinal fluid (CSF) and plasma candidate biomarkers are reported. METHODS: Six academic EADC centres recruited 49 subjects (healthy controls, subjects with mild cognitive impairment (MCI) and AD). We measured CSF beta-amyloid 42 (CSF Abeta42), total tau-protein (t-tau), phosphorylated tau-proteins (P-tau181, P-tau231), plasma beta-amyloid 40 and 42 (Abeta40/Abeta42). Immediate fresh shipment was compared to freezing and later shipment on dry ice. RESULTS: CSF T-tau (fresh samples) was increased in AD versus controls (p=0.049), CSF Abeta42 (frozen samples) was decreased in MCI and AD (p=0.02), as well as plasma Abeta40 (fresh and frozen samples) in AD (p=0.049 and p=0.016). Pooled values of neurochemical parameters and ratios thereof were different between centres (p<0.005). Analysis of frozen samples yielded higher diagnostic accuracy than immediate fresh shipment with 100% (fresh: 100%) correctly classified in control subjects, 100% (78%) in MCI, 91% (91%) in AD. CONCLUSION: The use of frozen rather than fresh samples renders higher diagnostic accuracy within a multicentre context. We confirmed the feasibility of a multicentre AD biomarker programme for future clinical trials.
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| 13. |
- Cacciani, Nicola, et al.
(författare)
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Age related differences in diaphragm muscle fiber response to mid/long term controlled mechanical ventilation
- 2014
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Ingår i: Experimental Gerontology. - : Elsevier BV. - 0531-5565 .- 1873-6815. ; 59, s. 28-33
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Critically ill intensive care patients are subjected to controlled mechanical ventilation (CMV) which has an important association in triggering the impaired muscle function and the consequent delayed weaning from the respirator. AIM: The main aim of this study was to measure the effects of age and CMV over a period up to 5days on rat diaphragm muscle fibers, more specifically focusing on the changes in fiber structure and function. METHODS: Diaphragm muscle fiber cross-sectional area (CSA) and force generating capacity were measured in young (6months) and old (28-32months) rats in response to five days of CMV. To investigate the biological age of the old rats in this rat strain (F344 BN hybrid), a second set of experiments comparing muscle fiber size and specific force (maximum force normalized to CSA) was investigated in fast- and slow-twitch distal hind limb muscles in 3 different age groups: young adults (6months), middle aged (18months) and old rats (28months). RESULTS: This study shows an unexpected response of the diaphragm fibers to 5days CMV, demonstrating an increased CSA (p<0.001) in both young and old animals. Furthermore, an observed decreased maximum force of 39.8-45.2% (p<0.001) in both young and old animals compared with controls resulted in a dramatic loss of specific force. We suggest that this increase in CSA and decrease in specific force observed in both the young and old diaphragm fibers is an ineffective compensatory hypertrophy in response to the CMV. These results demonstrate an important mechanism of significant importance for the weaning problems associated with mechanical ventilation.
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| 14. |
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| 15. |
- Cedernaes, Jonathan, et al.
(författare)
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Efficacy of antibody-based therapies to treat Alzheimer's disease : Just a matter of timing?
- 2014
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Ingår i: Experimental Gerontology. - : Elsevier BV. - 0531-5565 .- 1873-6815. ; 57, s. 104-106
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Tidskriftsartikel (refereegranskat)abstract
- A pharmaceutical intervention that has received great attention in recent years for treating Alzheimer's disease (AD) is the use of antibodies targeting amyloid beta (A beta) in the brain, as the formation of A beta plaques is considered as being the driving force for the development and progression of AD. Recently, a Phase III trial in patients with mild-to-moderate AD has provided ambivalent evidence for the efficacy of this intervention. In this trial, the intravenous administration of bapineuzumab, a monoclonal antibody targeting A beta in the brain, for 78 weeks led to a reduction of cerebrospinal fluid levels of phosphorylated tau and evidence for lower A beta accumulation in the brain of AD patients who carried APOE epsilon 4. However, this treatment did not improve clinical outcomes (e.g. the rate of cognitive decline) in these patients. Similar null results with respect to the rate of cognitive decline were found in a separate Phase III clinical trial after treatment with solanezumab. Based on these findings, one conclusion could be that antibodies targeting A beta in the brain may unfold their highest efficacy when given before the development of clinical AD symptoms, i.e. during a period where neurodegeneration but not cognitive loss represents the major pathology. Another conclusion could be that antibody-based pharmaceutical interventions may fail to slow the progress of cognitive loss in patients who have AD because of their solely pharmaceutical therapeutic approach. Leisure activities that require patients' mental and physical abilities (e.g. exercise) are associated with a reduced risk of developing dementia. In the same manner, they may help to curb the progress of this devastating disease. Thus, combining the use of antibodies targeting A beta with therapeutic strategies that require patients' mental and physical abilities might help tackle the neurodegenerative dynamics and cognitive loss both in patients with AD, and its prodromal state, mild cognitive impairment.
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| 16. |
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| 17. |
- Díaz, Miguel, Högskoleadjunkt, et al.
(författare)
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The effects of resveratrol on aging vessels
- 2016
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Ingår i: Experimental Gerontology. - : Elsevier. - 0531-5565 .- 1873-6815. ; 85:1, s. 41-47
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Forskningsöversikt (refereegranskat)
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| 18. |
- Edholm, Peter, 1977-, et al.
(författare)
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Muscle mass and aerobic capacity in older women : Impact of regular exercise at middle age
- 2021
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Ingår i: Experimental Gerontology. - : Elsevier. - 0531-5565 .- 1873-6815. ; 147
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The impact of regular exercise habits at middle-age on muscle mass and function at old age remains inconclusive. While regular exercise likely represents a primary source of health-enhancing physical activity (PA), the physical demand of occupation needs to be considered. Additionally, PA level at old age should be taken into account in order to elucidate true associations between past exercise behaviors and muscle mass and function at old age. Therefore, the aim of the study was to examine the impact of regular exercise habits during middle age years on muscle mass and physical function at old age, while considering occupation and objectively assessed PA level at old age.METHODS: Self-reported leisure-time PA during middle age years [35-65 years] and present accelerometer-derived PA level were assessed in a population of community-dwelling older women (65-70 years; n = 112). Participants who accumulated at least 600 MET-min of PA per week during middle age years were classified as physically active. Skeletal muscle mass index (SMI), aerobic fitness and maximal isometric arm and leg strength were determined. Analyses of differences in muscle mass and physical function between physically active and inactive at middle age were adjusted by present PA, adiposity level, and the physical demand of former occupation (sedentary vs manual).RESULTS: Participants accumulating at least 600 MET-min of exercise-related activities during middle-age years had higher aerobic fitness (P < 0.01) and SMI (P < 0.05) at old age compared to their less active peers. Notably, these beneficial impacts were driven by exercise habits during late middle-age period [50 to 65 years], and remained significant after further adjustment by the physical demand of former occupation and present PA behavior at old age. Finally, middle-age engagement in exercise-related activities had no influence on maximal arm and leg isometric strength at old age.CONCLUSION: Our findings highlight the importance of engaging in regular PA of at least moderate intensity during middle age years in order to promote benefits at the level of muscle mass and aerobic fitness. This clearly supports the potential of PA in delaying aerobic capacity impairment and the occurrence of clinically manifest sarcopenia at old age.
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| 19. |
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| 20. |
- Gardner, Michael, et al.
(författare)
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Gender and telomere length : Systematic review and meta-analysis
- 2014
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Ingår i: Experimental Gerontology. - : Elsevier. - 0531-5565 .- 1873-6815. ; 51, s. 15-27
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Forskningsöversikt (refereegranskat)abstract
- Background: It is widely believed that females have longer telomeres than males, although results from studies have been contradictory. Methods: We carried out a systematic review and meta-analyses to test the hypothesis that in humans, females have longer telomeres than males and that this association becomes stronger with increasing age. Searches were conducted in EMBASE and MEDLINE (by November 2009) and additional datasets were obtained from study investigators. Eligible observational studies measured telomeres for both females and males of any age, had a minimum sample size of 100 and included participants not part of a diseased group. We calculated summary estimates using random-effects meta-analyses. Heterogeneity between studies was investigated using sub-group analysis and meta-regression. Results: Meta-analyses from 36 cohorts (36,230 participants) showed that on average females had longer telomeres than males (standardised difference in telomere length between females and males 0.090, 95% CI 0.015, 0.166; age-adjusted). There was little evidence that these associations varied by age group (p = 1.00) or cell type (p = 0.29). However, the size of this difference did vary by measurement methods, with only Southern blot but neither real-time PCR nor Flow-FISH showing a significant difference. This difference was not associated with random measurement error. Conclusions: Telomere length is longer in females thanmales, although this difference was not universally found in studies that did not use Southern blot methods. Further research on explanations for the methodological differences is required. (C) 2013 Published by Elsevier Inc.
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