| 1. |
- Fjell, A. M., et al.
(författare)
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Self-reported Sleep Problems Related to Amyloid Deposition in Cortical Regions with High HOMER1 Gene Expression
- 2020
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Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 30:4, s. 2144-2156
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Tidskriftsartikel (refereegranskat)abstract
- Sleep problems are related to the elevated levels of the Alzheimer's disease (AD) biomarker beta-amyloid (AD) Hypotheses about the causes of this relationship can be generated from molecular markers of sleep problems identified in rodents. A major marker of sleep deprivation is Homerla, a neural protein coded by the HOMER1 gene, which has also been implicated in brain A beta accumulation. Here, we tested whether the relationship between cortical A beta accumulation and self-reported sleep quality, as well as changes in sleep quality over 3 years, was stronger in cortical regions with high HOMER1 mRNA expression levels. In a sample of 154 cognitively healthy older adults, A beta correlated with poorer sleep quality cross-sectionally and longitudinally (n = 62), but more strongly in the younger than in older individuals. Effects were mainly found in regions with high expression of HOMER1. The anatomical distribution of the sleep-A beta relationship followed closely the A beta accumulation pattern in 69 patients with mild cognitive impairment or AD. Thus, the results indicate that the relationship between sleep problems and A beta accumulation may involve Homer1 activity in the cortical regions, where harbor A beta deposits in AD. The findings may advance our understanding of the relationship between sleep problems and AD risk.
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| 2. |
- Aksnes, M., et al.
(författare)
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Matrix metalloproteinases are associated with brain atrophy in cognitively unimpaired individuals
- 2023
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Ingår i: Neurobiology of Aging. - 0197-4580. ; 131, s. 11-23
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Tidskriftsartikel (refereegranskat)abstract
- Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have been linked to age-related neurodegeneration and Alzheimer's disease (AD), but their role in normal aging is poorly understood. We used linear mixed models to determine if baseline or rate of yearly change in cerebrospinal fluid (CSF) levels of MMP-2; MMP-3; MMP-10; TIMP-123 (composite of TIMP-1, TIMP-2, and TIMP-3); or TIMP-4 predicted changes in bilateral entorhinal cortex thickness, hippocampal volume, or lateral ventricle volume in cognitively unimpaired individuals. We also assessed effects on the CSF AD biomarkers amyloid-& beta;42 and phosphorylated tau181. Low baseline levels of MMP-3 predicted larger ventricle volumes and more entorhinal cortex thinning. Increased CSF MMP-2 levels over time predicted more entorhinal thinning, hippocampal atrophy, and ventricular expansion, while increased TIMP-123 over time predicted ventricular expansion. No MMP/TIMPs predicted changes in CSF AD biomarkers. Notably, we show for the first time that longitudinal increases in MMP-2 and TIMP-123 levels may predict age-associated brain atrophy. In conclusion, MMPs and TIMPs may play a role in brain atrophy in cognitively unimpaired aging. & COPY; 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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| 3. |
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| 4. |
- Vidal-Pineiro, D., et al.
(författare)
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Relationship between cerebrospinal fluid neurodegeneration biomarkers and temporal brain atrophy in cognitively healthy older adults
- 2022
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 116, s. 80-91
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Tidskriftsartikel (refereegranskat)abstract
- It is unclear whether cerebrospinal fluid (CSF) biomarkers of neurodegeneration predict brain atrophy in cognitively healthy older adults, whether these associations can be explained by phosphorylated tau181 (p-tau) and the 42 amino acid form of amyloid-beta (A beta 42) biomarkers, and which neural substrates may drive these associations. We addressed these questions in 2 samples of cognitively healthy older adults who underwent longitudinal structural MRI up to 7 years and had baseline CSF levels of heart-type fatty-acid binding protein (FABP3) = , total-tau, neurogranin, and neurofilament light (NFL) (n = 189, scans = 721). The results showed that NFL, total-tau, and FABP3 predicted entorhinal thinning and hippocampal atrophy. Brain atrophy was not moderated by A beta 42 and the associations between NFL and FABP3 with brain atrophy were independent of p-tau. The spatial pattern of cortical atrophy associated with the biomarkers overlapped with neurogenetic profiles associated with expression in the axonal (total-tau, NFL) and dendritic (neurogranin) components. CSF biomarkers of neurodegeneration are useful for predicting specific features of brain atrophy in older adults, independently of amyloid and tau pathology biomarkers. (C) 2022 The Author(s). Published by Elsevier Inc.
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| 5. |
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| 6. |
- Capogna, E., et al.
(författare)
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Associations of neuroinflammatory IL-6 and IL-8 with brain atrophy, memory decline, and core AD biomarkers-in cognitively unimpaired older adults
- 2023
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Ingår i: Brain, behavior, and immunity. - 0889-1591 .- 1090-2139. ; 113, s. 56-65
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Tidskriftsartikel (refereegranskat)abstract
- Concentrations of pro-inflammatory cytokines -interleukin-6 (IL-6) and interleukin-8 (IL-8) - are increased with age and in Alzheimer's disease (AD). It is not clear whether concentrations of IL-6 and IL-8 in the central nervous system predict later brain and cognitive changes over time nor whether this relationship is mediated by core AD biomarkers. Here, 219 cognitively healthy older adults (62-91 years), with baseline cerebrospinal fluid (CSF) measures of IL-6 and IL-8 were followed over time - up to 9 years - with assessments that included cognitive function, structural magnetic resonance imaging, and CSF measurements of phosphorylated tau (p-tau) and amyloid-& beta; (A & beta;-42) concentrations (for a subsample). Higher baseline CSF IL-8 was associated with better memory performance over time in the context of lower levels of CSF p-tau and p-tau/A & beta;-42 ratio. Higher CSF IL-6 was related to less CSF p-tau changes over time. The results are in line with the hypothesis suggesting that an upregulation of IL-6 and IL-8 in the brain may play a neuroprotective role in cognitively healthy older adults with lower load of AD pathology.
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| 7. |
- Fjell, Anders M., et al.
(författare)
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Poor Self-Reported Sleep is Related to Regional Cortical Thinning in Aging but not Memory Decline-Results From the Lifebrain Consortium
- 2021
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Ingår i: Cerebral Cortex. - : Oxford University Press. - 1047-3211 .- 1460-2199. ; 31:4, s. 1953-1969
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Tidskriftsartikel (refereegranskat)abstract
- We examined whether sleep quality and quantity are associated with cortical and memory changes in cognitively healthy participants across the adult lifespan. Associations between self-reported sleep parameters (Pittsburgh Sleep Quality Index, PSQI) and longitudinal cortical change were tested using five samples from the Lifebrain consortium (n = 2205, 4363 MRIs, 18-92 years). In additional analyses, we tested coherence with cell-specific gene expression maps from the Allen Human Brain Atlas, and relations to changes in memory performance. "PSQI # 1 Subjective sleep quality" and "PSQI #5 Sleep disturbances" were related to thinning of the right lateral temporal cortex, with lower quality and more disturbances being associated with faster thinning. The association with "PSQI #5 Sleep disturbances" emerged after 60 years, especially in regions with high expression of genes related to oligodendrocytes and S1 pyramidal neurons. None of the sleep scales were related to a longitudinal change in episodic memory function, suggesting that sleep-related cortical changes were independent of cognitive decline. The relationship to cortical brain change suggests that self-reported sleep parameters are relevant in lifespan studies, but small effect sizes indicate that self-reported sleep is not a good biomarker of general cortical degeneration in healthy older adults.
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| 8. |
- Henjum, K., et al.
(författare)
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Cerebrospinal fluid catecholamines in Alzheimer's disease patients with and without biological disease
- 2022
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Noradrenergic and dopaminergic neurons are involved in cognitive functions, relate to behavioral and psychological symptoms in dementia and are affected in Alzheimer's disease (AD). Amyloid plaques (A), neurofibrillary tangles (T) and neurodegeneration (N) hallmarks the AD neuropathology. Today, the AT(N) pathophysiology can be assessed through biomarkers. Previous studies report cerebrospinal fluid (CSF) catecholamine concentrations in AD patients without biomarker refinement. We explored if CSF catecholamines relate to AD clinical presentation or neuropathology as reflected by CSF biomarkers. CSF catecholamines were analyzed in AD patients at the mild cognitive impairment (MCI; n = 54) or dementia stage (n = 240) and in cognitively unimpaired (n = 113). CSF biomarkers determined AT status and indicated synaptic damage (neurogranin). The AD patients (n = 294) had higher CSF noradrenaline and adrenaline concentrations, but lower dopamine concentrations compared to the cognitively unimpaired (n = 113). AD patients in the MCI and dementia stage of the disease had similar CSF catecholamine concentrations. In the CSF neurogranin positively associated with noradrenaline and adrenaline but not with dopamine. Adjusted regression analyses including AT status, CSF neurogranin, age, gender, and APOE epsilon 4 status verified the findings. In restricted analyses comparing A+T+ patients to A-T- cognitively unimpaired, the findings for CSF adrenaline remained significant (p < 0.001) but not for CSF noradrenaline (p = 0.07) and CSF dopamine (p = 0.33). There were no differences between A+T+ and A-T- cognitively unimpaired. Thus, we find alterations in CSF catecholamines in symptomatic AD and the CSF adrenergic transmitters to increase simultaneously with synaptic damage as indexed by CSF neurogranin.
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| 9. |
- Hov, K. R., et al.
(författare)
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Cerebrospinal Fluid S100B and Alzheimer's Disease Biomarkers in Hip Fracture Patients with Delirium
- 2017
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Ingår i: Dementia and Geriatric Cognitive Disorders Extra. - : S. Karger AG. - 1664-5464. ; 7:3, s. 374-385
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: This study aimed to investigate the relationship between cerebrospinal fluid (CSF) S100B astrocyte-derived protein and delirium and to perform stratified analyses according to clinical and CSF markers of dementia. Methods: We performed a prospective cohort study in a university hospital setting. The participants were patients admitted for hip fracture (n = 98) or for elective surgery (n = 50). Delirium was assessed daily perioperatively in hip fracture patients using the Confusion Assessment Method. A consensus-based diagnosis of prefracture dementia was made using all available information. CSF was drawn at the onset of spinal anesthesia. S100B and phosphorylated tau (P-tau) concentrations were measured using electro-chemiluminescence immunoassay and enzyme-linked immunosorbent assays, respectively. Results: In the hip fracture population (n = 98) there was no significant difference in CSF S100B concentrations between patients with ongoing preoperative (i.e., prevalent) delirium (n = 36, median [interquartile range] 1.11 mu g/L [0.91-1.29]) and patients who never developed delirium (n = 46, 1.08 mu g/L [0.92-1.28], p = 0.92). In patients without preoperative delirium, those who developed delirium postoperatively (i.e., incident delirium) (n = 16, 1.38 mu g/L [1.08-1.62]) had higher concentrations of S100B than the 46 who never did (p = 0.013). This difference was confined to patients with pathological concentrations of P-tau (= 60 ng/L, n = 38). We also found that P-tau and S100B were correlated in CSF in the elective surgery patients. Conclusions: CSF S100B was elevated in patients with incident delirium who also had pathological levels of the Alzheimer disease biomarker P-tau, suggesting vulnerability caused by a preexisting process of astrocytic activation and tau pathology. (c) 2017 The Author(s) Published by S. Karger AG, Basel.
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| 10. |
- Emanuelsson, Eva U., et al.
(författare)
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Parameterization of Thermal Properties of Aging Secondary Organic Aerosol Produced by Photo-Oxidation of Selected Terpene Mixtures
- 2014
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 48:11, s. 6168-6176
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Tidskriftsartikel (refereegranskat)abstract
- Formation and evolution of secondary organic aerosols (SOA) from biogenic VOCs influences the Earth's radiative balance. We have examined the photo-oxidation and aging of boreal terpene mixtures in the SAPHIR simulation chamber. Changes in thermal properties and chemical composition, deduced from mass spectrometric measurements, were providing information on the aging of biogenic SOA produced under ambient solar conditions. Effects of precursor mixture, concentration, and photochemical oxidation levels (OH exposure) were evaluated. OH exposure was found to be the major driver in the long term photochemical transformations, i.e., reaction times of several hours up to days, of SOA and its thermal properties, whereas the initial concentrations and terpenoid mixtures had only minor influence. The volatility distributions were parametrized using a sigmoidal function to determine T-VFR0.5 (the temperature yielding a 50% particle volume fraction remaining) and the steepness of the volatility distribution. T-VFR0.5 increased by 0.3 +/- 0.1% (ca. 1 K), while the steepness increased by 0.9 +/- 0.3% per hour of 1 x 10(6) cm(-3) OH exposure. Thus, aging reduces volatility and increases homogeneity of the vapor pressure distribution, presumably because highly volatile fractions become increasingly susceptible to gas phase oxidation, while less volatile fractions are less reactive with gas phase OH.
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| 11. |
- Fjell, Anders M., et al.
(författare)
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Is short sleep bad for the brain? : Brain structure and cognitive function in short sleepers
- 2023
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Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 43:28, s. 5241-5250
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Tidskriftsartikel (refereegranskat)abstract
- Many sleep less than recommended without experiencing daytime sleepiness. According to prevailing views, short sleep increases risk of lower brain health and cognitive function. Chronic mild sleep deprivation could cause undetected sleep debt, negatively affecting cognitive function and brain health. However, it is possible that some have less sleep need and are more resistant to negative effects of sleep loss. We investigated this using a cross-sectional and longitudinal sample of 47,029 participants of both sexes (20-89 years) from the Lifebrain consortium, Human Connectome project (HCP) and UK Biobank (UKB), with measures of self-reported sleep, including 51,295 MRIs of the brain and cognitive tests. A total of 740 participants who reported to sleep <6 h did not experience daytime sleepiness or sleep problems/disturbances interfering with falling or staying asleep. These short sleepers showed significantly larger regional brain volumes than both short sleepers with daytime sleepiness and sleep problems (n = 1742) and participants sleeping the recommended 7-8 h (n = 3886). However, both groups of short sleepers showed slightly lower general cognitive function (GCA), 0.16 and 0.19 SDs, respectively. Analyses using accelerometer-estimated sleep duration confirmed the findings, and the associations remained after controlling for body mass index, depression symptoms, income, and education. The results suggest that some people can cope with less sleep without obvious negative associations with brain morphometry and that sleepiness and sleep problems may be more related to brain structural differences than duration. However, the slightly lower performance on tests of general cognitive abilities warrants closer examination in natural settings.SIGNIFICANCE STATEMENT: Short habitual sleep is prevalent, with unknown consequences for brain health and cognitive performance. Here, we show that daytime sleepiness and sleep problems are more strongly related to regional brain volumes than sleep duration. However, participants sleeping ≤6 h had slightly lower scores on tests of general cognitive function (GCA). This indicates that sleep need is individual and that sleep duration per se is very weakly if at all related brain health, while daytime sleepiness and sleep problems may show somewhat stronger associations. The association between habitual short sleep and lower scores on tests of general cognitive abilities must be further scrutinized in natural settings.
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| 12. |
- Fjell, Anders M., et al.
(författare)
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No phenotypic or genotypic evidence for a link between sleep duration and brain atrophy
- 2023
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Ingår i: Nature Human Behaviour. - : Springer Nature. - 2397-3374. ; 7:11, s. 2008-2022
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Tidskriftsartikel (refereegranskat)abstract
- Short sleep is held to cause poorer brain health, but is short sleep associated with higher rates of brain structural decline? Analysing 8,153 longitudinal MRIs from 3,893 healthy adults, we found no evidence for an association between sleep duration and brain atrophy. In contrast, cross-sectional analyses (51,295 observations) showed inverse U-shaped relationships, where a duration of 6.5 (95% confidence interval, (5.7, 7.3)) hours was associated with the thickest cortex and largest volumes relative to intracranial volume. This fits converging evidence from research on mortality, health and cognition that points to roughly seven hours being associated with good health. Genome-wide association analyses suggested that genes associated with longer sleep for below-average sleepers were linked to shorter sleep for above-average sleepers. Mendelian randomization did not yield evidence for causal impacts of sleep on brain structure. The combined results challenge the notion that habitual short sleep causes brain atrophy, suggesting that normal brains promote adequate sleep duration—which is shorter than current recommendations.
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| 13. |
- Fjell, Anders M., et al.
(författare)
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Self-reported sleep relates to hippocampal atrophy across the adult lifespan : results from the Lifebrain consortium
- 2020
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Ingår i: Sleep. - : Oxford University Press. - 0161-8105 .- 1550-9109. ; 43:5
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Poor sleep is associated with multiple age-related neurodegenerative and neuropsychiatric conditions. The hippocampus plays a special role in sleep and sleep-dependent cognition, and accelerated hippocampal atrophy is typically seen with higher age. Hence, it is critical to establish how the relationship between sleep and hippocampal volume loss unfolds across the adult lifespan.Methods: Self-reported sleep measures and MRI-derived hippocampal volumes were obtained from 3105 cognitively normal participants (18–90 years) from major European brain studies in the Lifebrain consortium. Hippocampal volume change was estimated from 5116 MRIs from 1299 participants for whom longitudinal MRIs were available, followed up to 11 years with a mean interval of 3.3 years. Cross-sectional analyses were repeated in a sample of 21,390 participants from the UK Biobank.Results: No cross-sectional sleep—hippocampal volume relationships were found. However, worse sleep quality, efficiency, problems, and daytime tiredness were related to greater hippocampal volume loss over time, with high scorers showing 0.22% greater annual loss than low scorers. The relationship between sleep and hippocampal atrophy did not vary across age. Simulations showed that the observed longitudinal effects were too small to be detected as age-interactions in the cross-sectional analyses.Conclusions: Worse self-reported sleep is associated with higher rates of hippocampal volume decline across the adult lifespan. This suggests that sleep is relevant to understand individual differences in hippocampal atrophy, but limited effect sizes call for cautious interpretation.
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| 14. |
- Johansson, Julia M., et al.
(författare)
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The European heat wave of 2018 and its promotion of the ozone climate penalty in southwest Sweden
- 2020
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Ingår i: Boreal Environment Research. - 1239-6095 .- 1797-2469. ; 25, s. 39-50
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Tidskriftsartikel (refereegranskat)abstract
- The ozone concentration ([O-3]), temperature (T) and vapour pressure deficit (VPD) during the 2018 heat wave (HW) was compared with conditions from 2013-2017. The study included one coastal and two inland sites in southwest Sweden. The positive relationship between [O-3] and T was stronger in 2018. The average daytime T from April-September was higher by 2.0-2.4 degrees C in 2018. The VPD was strongly and positively affected by the 2018 HW. The daytime mean [O-3] was enhanced by 7-12% in 2018. The relationship between hourly daytime [O-3] and T, as well as that between the daily maximum [O-3] and daily maximum T, was steeper in 2018. The stronger promotion of [O-3] by T in 2018 was possibly partly a result of dry conditions causing stomatal closure of vegetation and thus a weaker O-3 sink. If HWs like that in 2018 become more common, they can be expected to promote higher [O-3] and risk larger health and ecosystem effects.
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| 15. |
- Neerland, B. E., et al.
(författare)
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Fatty Acid-Binding Protein 3 in Cerebrospinal Fluid of Hip Fracture Patients with Delirium
- 2020
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Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 77:1, s. 183-190
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Tidskriftsartikel (refereegranskat)abstract
- Background: Delirium is associated with dementia and thus biomarkers reflecting neurodegeneration are of interest. Fatty acid-binding protein 3 (FABP3) is a cytoplasmic neuronal protein that has been isolated from the brain. It is released following brain injury and concentrations in cerebrospinal fluid (CSF) are also higher in neurodegenerative disorders such as Alzheimer's disease (AD). Objective: To examine the relationship between CSF FABP3 concentration and delirium in hip fracture patients compared to a group of cognitively normal controls. Methods: CFS FABP3 concentration was measured in 128 hip fracture patients with (n = 71) and without (n = 57) delirium, and in cognitively unimpaired adults >= 64 years (n = 124) undergoing elective surgery. Results: CSF FABP3 (pg/ml) concentration (median (IQR)) was higher in hip-fracture patients compared to cognitively normal controls (5.7 (4.2-7.7) versus 4.5 (3.4-6.1), p < 0.001). There was a significant weak correlation between age and CSF FABP3 (rho = 0.3, p < 0.001). After adjustment for age, the association between CSF FABP3 and hip-fracture was no longer statistically significant (13 = 0.05, p = 0.5). There were no significant differences in CSF FABP3 concentration between hip fracture patients with (5.4 (4.1-8.2)) and without (5.8 (4.2-7.2)) delirium. CSF FABP3 concentration correlated positively with CSF AD biomarkers p-tau (rho = 0.7, p <0.01) and t-tau (rho = 0.7, p < 0.01). Conclusion: CSF FABP3 concentrations were higher in hip fracture patients compared with cognitively normal older adults, indicating ongoing age-related neurodegeneration in these patients. There were no differences of CSF FABP3 concentrations across delirium groups, suggesting that neuronal damage or degeneration reflected by FABP3 may not be directly linked to delirium pathophysiology.
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