| 1. |
- Maddock, Jane, et al.
(författare)
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Vitamin D and cognitive function : A Mendelian randomisation study.
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- The causal nature of the association between hypovitaminosis D and poor cognitive function in mid- to later-life is uncertain. Using a Mendelian randomisation(MR) approach, we examined the causal relationship between 25(OH)D and cognitive function. Data came from 172,349 participants from 17 cohorts. DHCR7(rs12785878), CYP2R1 rs12794714) and their combined synthesis score were chosen to proxy 25(OH)D. Cognitive tests were standardised into global and memory scores. Analyses were stratified by 25(OH)D tertiles, sex and age. Random effects meta-analyses assessed associations between 25(OH)D and cognitive function. Associations of serum 25(OH)D with global and memory-related cognitive function were non-linear (lower cognitive scores for both low and high 25(OH)D, p curvature ≤ 0.006), with much of the curvature attributed to a single study. DHCR7, CYP2R1, and the synthesis score were associated with small reductions in 25(OH)D per vitamin D-decreasing allele. However, coefficients for associations with global or memory-related cognitive function were non-significant and in opposing directions for DHCR7 and CYP2R1, with no overall association observed for the synthesis score. Coefficients for the synthesis score and global and memory cognition were similar when stratified by 25(OH)D tertiles, sex and age. We found no evidence for serum 25(OH)D concentration as a causal factor for cognitive performance in mid- to later life.
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| 2. |
- Nabers, Andreas, et al.
(författare)
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Amyloid blood biomarker detects Alzheimer's disease
- 2018
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Ingår i: EMBO Molecular Medicine. - : EMBO. - 1757-4676 .- 1757-4684. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) is currently incurable, but there is general agreement that a minimally invasive blood biomarker for screening in preclinical stages would be crucial for future therapy. Diagnostic tools for detection of AD are either invasive like cerebrospinal fluid (CSF) biomarkers or expensive such as positron emission tomography (PET) scanning. Here, we determine the secondary structure change of amyloid-β (Aβ) in human blood. This change used as blood amyloid biomarker indicates prodromal AD and correlates with CSF AD biomarkers and amyloid PET imaging in the cross-sectional BioFINDER cohort. In a further population-based longitudinal cohort (ESTHER), the blood biomarker detected AD several years before clinical diagnosis in baseline samples with a positive likelihood ratio of 7.9; that is, those who were diagnosed with AD over the years were 7.9 times more likely to test positive. This assay may open avenues for blood screening of early AD stages as a funnel for further more invasive and expensive tests.
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| 3. |
- Ordóñez-Mena, José Manuel, et al.
(författare)
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Pre-diagnostic vitamin D concentrations and cancer risks in older individuals : an analysis of cohorts participating in the CHANCES consortium
- 2016
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 31:3, s. 311-323
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Tidskriftsartikel (refereegranskat)abstract
- The associations of circulating 25-hydroxyvitamin D [25(OH)D] concentrations with total and site-specific cancer incidence have been examined in several epidemiological studies with overall inconclusive findings. Very little is known about the association of vitamin D with cancer incidence in older populations. We assessed the association of pre-diagnostic serum 25(OH)D levels with incidence of all cancers combined and incidence of lung, colorectal, breast, prostate and lymphoid malignancies among older adults. Pre-diagnostic 25(OH)D concentrations and cancer incidence were available in total for 15,486 older adults (mean age 63, range 50-84 years) participating in two cohort studies: ESTHER (Germany) and TROMSØ (Norway); and a subset of previously published nested-case control data from a another cohort study: EPIC-Elderly (Greece, Denmark, Netherlands, Spain and Sweden) from the CHANCES consortium on health and aging. Cox proportional hazards or logistic regression were used to derive multivariable adjusted hazard and odds ratios, respectively, and their 95 % confidence intervals across 25(OH)D categories. Meta-analyses with random effects models were used to pool study-specific risk estimates. Overall, lower 25(OH)D concentrations were not significantly associated with increased incidence of most of the cancers assessed. However, there was some evidence of increased breast cancer and decreased lymphoma risk with higher 25(OH)D concentrations. Our meta-analyses with individual participant data from three large European population-based cohort studies provide at best limited support for the hypothesis that vitamin D may have a major role in cancer development and prevention among European older adults.
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| 4. |
- Raina, Parminder, et al.
(författare)
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The Combined Effect of Cancer and Cardiometabolic Conditions on the Mortality Burden in Older Adults
- 2019
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press. - 1079-5006 .- 1758-535X. ; 74:3, s. 366-372
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Tidskriftsartikel (refereegranskat)abstract
- The number of older people living with cancer and cardiometabolic conditions is increasing, but little is known about how specific combinations of these conditions impact mortality.A total of 22,692 participants aged 65 years and older from four international cohorts were followed-up for mortality for an average of 10 years (8,596 deaths). Data were harmonized across cohorts and mutually exclusive groups of disease combinations were created for cancer, myocardial infarction (MI), stroke, and diabetes at baseline. Cox proportional hazards models for all-cause mortality were used to estimate the age- and sex-adjusted hazard ratio and rate advancement period (RAP) (in years).At baseline, 23.6% (n = 5,116) of participants reported having one condition and 4.2% (n = 955) had two or more conditions. Data from all studies combined showed that the RAP increased with each additional condition. Diabetes advanced the rate of dying by the most years (5.26 years; 95% confidence interval [CI], 4.536.00), but the effect of any single condition was smaller than the effect of disease combinations. Some combinations had a significantly greater impact on the period by which the rate of death was advanced than others with the same number of conditions, for example, 10.9 years (95% CI, 9.412.6) for MI and diabetes versus 6.4 years (95% CI, 4.38.5) for cancer and diabetes.Combinations of cancer and cardiometabolic conditions accelerate mortality rates in older adults differently. Although most studies investigating mortality associated with multimorbidity used disease counts, these provide little guidance for managing complex patients as they age.
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| 5. |
- Rädecker, Nils, et al.
(författare)
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Heat stress reduces the contribution of diazotrophs to coral holobiont nitrogen cycling
- 2022
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Ingår i: The ISME Journal. - : Springer Science and Business Media LLC. - 1751-7362 .- 1751-7370. ; 16, s. 1110-1118
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Tidskriftsartikel (refereegranskat)abstract
- Efficient nutrient cycling in the coral-algal symbiosis requires constant but limited nitrogen availability. Coral-associated diazotrophs, i.e., prokaryotes capable of fixing dinitrogen, may thus support productivity in a stable coral-algal symbiosis but could contribute to its breakdown when overstimulated. However, the effects of environmental conditions on diazotroph communities and their interaction with other members of the coral holobiont remain poorly understood. Here we assessed the effects of heat stress on diazotroph diversity and their contribution to holobiont nutrient cycling in the reef-building coral Stylophora pistillata from the central Red Sea. In a stable symbiotic state, we found that nitrogen fixation by coral-associated diazotrophs constitutes a source of nitrogen to the algal symbionts. Heat stress caused an increase in nitrogen fixation concomitant with a change in diazotroph communities. Yet, this additional fixed nitrogen was not assimilated by the coral tissue or the algal symbionts. We conclude that although diazotrophs may support coral holobiont functioning under low nitrogen availability, altered nutrient cycling during heat stress abates the dependence of the coral host and its algal symbionts on diazotroph-derived nitrogen. Consequently, the role of nitrogen fixation in the coral holobiont is strongly dependent on its nutritional status and varies dynamically with environmental conditions.
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