| 1. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 2. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 3. |
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| 4. |
- Escott-Price, Valentina, et al.
(författare)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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| 5. |
- Pilotto, Alberto, et al.
(författare)
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Relation of Statin Use and Mortality in Community-Dwelling Frail Older Patients With Coronary Artery Disease
- 2016
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149 .- 1879-1913. ; 118:11, s. 1624-1630
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Tidskriftsartikel (refereegranskat)abstract
- Clinical decision-making for statin treatment in older patients with coronary artery disease (CAD) is under debate, particularly in community-dwelling frail patients at high risk of death. In this retrospective observational study on 2,597 community-dwelling patients aged >= 65 years with a previous hospitalization for CAD, we estimated mortality risk assessed with the Multidimensional Prognostic Index (MPI), based on the Standardized Multidimensional Assessment Schedule for Adults and Aged Persons (SVaMA), used to determine accessibility to homecare services/nursing home admission in 2005 to 2013 in the Padua Health District, Veneto, Italy. Participants were categorized as having mild (MPI-SVaMA-1), moderate (MPI-SVaMA-2), and high (MPI-SVaMA-3) baseline mortality risk, and propensity score-adjusted hazard ratios (HRs) of 3-year mortality rate were calculated according to statin treatment in these subgroups. Greater MPI-SVaMA scores were associated with lower rates of statin treatment and higher 3-year mortality rate (MPI-SVaMA-1 = 23.4%; MPI-SVaMA-2 = 39.1%; MPI-SVaMA-3 = 76.2%). After adjusting for propensity score quintiles, statin treatment was associated with lower 3-year mortality risk irrespective of MPI-SVaMA group (HRs [95% confidence intervals] 0.45 [0.37 to 0.55], 0.44 [0.36 to 0.53], and 0.28 [0.21 to 0.39] in MPI-SVaMA-1,-2, and-3 groups, respectively [interaction test p = 0.202]). Subgroup analyses showed that statin treatment was also beneficial irrespective of age (HRs [95% confidence intervals] 0.38 [0.27 to 0.53], 0.45 [0.38 to 0.54], and 0.44 [0.37 to 0.54] in 65 to 74, 75 to 84, and Z85 year age groups, respectively [interaction test p = 0.597]). In conclusion, in community-dwelling frail older patients with CAD, statin treatment was significantly associated with reduced 3-year mortality rate irrespective of age and multidimensional impairment, although the frailest patients were less likely to be treated with statins.
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| 6. |
- Pilotto, Andrea, et al.
(författare)
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SARS-CoV-2 encephalitis is a cytokine release syndrome: evidences from cerebrospinal fluid analyses.
- 2021
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Ingår i: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. - : Oxford University Press (OUP). - 1537-6591. ; 73:9
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Tidskriftsartikel (refereegranskat)abstract
- Recent findings indicated that SARS-CoV-2 related neurological manifestations involve cytokine release syndrome along with endothelial activation, blood brain barrier dysfunction, and immune-mediated mechanisms. Very few studies have fully investigated the CSF correlates of SARS-CoV-2 encephalitis.Patients with PCR-confirmed SARS-CoV-2 infection and encephalitis (COV-Enc), encephalitis without SARS-CoV-2 infection (ENC) and healthy controls (HC) underwent an extended panel of CSF neuronal (NfL, T-tau), glial (GFAP, TREM2, YKL-40) and inflammatory biomarkers (IL-1β, IL-6, Il-8, TNF- α, CXCL-13 and β2-microglobulin).Thirteen COV-Enc, 21 ENC and 18 HC entered the study. In COV-Enc cases, CSF was negative for SARS-CoV-2 real-time PCR but exhibited increased IL-8 levels independently from presence of pleocytosis/hyperproteinorracchia. COV-Enc patients showed increased IL-6, TNF- α, and β2-microglobulin and glial markers (GFAP, sTREM-2, YKL-40) levels similar to ENC but normal CXCL13 levels. Neuronal markers NfL and T-Tau were abnormal only in severe cases.SARS-CoV-2-related encephalitis were associated with prominent glial activation and neuroinflammatory markers, whereas neuronal markers were increased in severe cases only. The pattern of CSF alterations suggested a cytokine-release syndrome as the main inflammatory mechanism of SARS-CoV-2 related encephalitis.
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| 7. |
- Angleman, Sara B., et al.
(författare)
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Multidimensional Prognostic Index in Association with Future Mortality and Number of Hospital Days in a Population-Based Sample of Older Adults : Results of the EU Funded MPI_AGE Project
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Background The Multidimensional Prognostic Index (MPI) has been found to predict mortality in patients with a variety of clinical conditions. We aimed to assess the association of the MPI with future mortality and number of in-hospital days for the first time in a population-based cohort. Methods The study population consisted of 2472 persons, aged 66-99 years, from the Swedish National Study on Aging and Care in Kungsholmen, Sweden, who underwent the baseline visit 2001-4, and were followed up >10 years for in-hospital days and >12 years for mortality. The MPI was a modified version of the original and aggregated seven domains (personal and instrumental activities of daily living, cognitive function, illness severity and comorbidity, number of medications, co-habitation status, and nutritional status). The MPI score was divided into risk groups: low, medium and high. Number of in-hospital days (within 1, 3 and 10 years) and mortality data were derived from official registries. All analyses were age-stratified (sexagenarians, septuagenarians, octogenarians, nonagenarians). Results During the follow-up 1331 persons (53.8%) died. Laplace regression models, suggested that median survival in medium risk groups varied by age from 2.2-3.6 years earlier than for those in the corresponding low risk groups (p = 0.002-p<0.001), and median survival in high risk groups varied by age from 3.8-9.0 years earlier than for corresponding low risk groups (p<0.001). For nonagenarians, the median age at death was 3.8 years earlier in the high risk group than for the low risk group (p<0.001). The mean number of in-hospital days increased significantly with higher MPI risk score within 1 and 3 years for people of each age group. Conclusion For the first time, the effectiveness of MPI has been verified in a population-based cohort. Higher MPI risk scores associated with more days in hospital and with fewer years of survival, across a broad and stratified age range.
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| 8. |
- Ashton, Nicholas J., et al.
(författare)
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A multicentre validation study of the diagnostic value of plasma neurofilament light
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- Increased cerebrospinal fluid neurofilament light (NfL) is a recognized biomarker for neurodegeneration that can also be assessed in blood. Here, we investigate plasma NfL as a marker of neurodegeneration in 13 neurodegenerative disorders, Down syndrome, depression and cognitively unimpaired controls from two multicenter cohorts: King's College London (n = 805) and the Swedish BioFINDER study (n = 1,464). Plasma NfL was significantly increased in all cortical neurodegenerative disorders, amyotrophic lateral sclerosis and atypical parkinsonian disorders. We demonstrate that plasma NfL is clinically useful in identifying atypical parkinsonian disorders in patients with parkinsonism, dementia in individuals with Down syndrome, dementia among psychiatric disorders, and frontotemporal dementia in patients with cognitive impairment. Data-driven cut-offs highlighted the fundamental importance of age-related clinical cut-offs for disorders with a younger age of onset. Finally, plasma NfL performs best when applied to indicate no underlying neurodegeneration, with low false positives, in all age-related cut-offs.
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| 9. |
- Attermeyer, Katrin, et al.
(författare)
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Carbon dioxide fluxes increase from day to night across European streams
- 2021
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Ingår i: Communications Earth & Environment. - : Springer Nature. - 2662-4435. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- Globally, inland waters emit over 2 Pg of carbon per year as carbon dioxide, of which the majority originates from streams and rivers. Despite the global significance of fluvial carbon dioxide emissions, little is known about their diel dynamics. Here we present a large-scale assessment of day- and night-time carbon dioxide fluxes at the water-air interface across 34 European streams. We directly measured fluxes four times between October 2016 and July 2017 using drifting chambers. Median fluxes are 1.4 and 2.1mmolm(-2) h(-1) at midday and midnight, respectively, with night fluxes exceeding those during the day by 39%. We attribute diel carbon dioxide flux variability mainly to changes in the water partial pressure of carbon dioxide. However, no consistent drivers could be identified across sites. Our findings highlight widespread day-night changes in fluvial carbon dioxide fluxes and suggest that the time of day greatly influences measured carbon dioxide fluxes across European streams. Diel patterns can greatly impact total stream carbon dioxide emissions, with 39% greater carbon dioxide flux during the night-time relative to the day-time, according to a study of 34 streams across Europe.
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| 10. |
- Bauckneht, Matteo, et al.
(författare)
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Associations among education, age, and the dementia with Lewy bodies (DLB) metabolic pattern: A European-DLB consortium project
- 2021
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Ingår i: Alzheimer's & Dementia. - : WILEY. - 1552-5260 .- 1552-5279. ; 17:8, s. 1277-1286
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Tidskriftsartikel (refereegranskat)abstract
- Introduction We assessed the influence of education as a proxy of cognitive reserve and age on the dementia with Lewy bodies (DLB) metabolic pattern. Methods Brain 18F-fluorodeoxyglucose positron emission tomography and clinical/demographic information were available in 169 probable DLB patients included in the European DLB-consortium database. Principal component analysis identified brain regions relevant to local data variance. A linear regression model was applied to generate age- and education-sensitive maps corrected for Mini-Mental State Examination score, sex (and either education or age). Results Age negatively covaried with metabolism in bilateral middle and superior frontal cortex, anterior and posterior cingulate, reducing the expression of the DLB-typical cingulate island sign (CIS). Education negatively covaried with metabolism in the left inferior parietal cortex and precuneus (making the CIS more prominent). Discussion These findings point out the importance of tailoring interpretation of DLB biomarkers considering the concomitant effect of individual, non-disease-related variables such as age and cognitive reserve.
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| 11. |
- Cruz-Jentoft, Alfonso J., et al.
(författare)
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Using the Multidimensional Prognostic Index (MPI) to improve cost-effectiveness of interventions in multimorbid frail older persons : results and final recommendations from the MPI_AGE European Project
- 2020
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Ingår i: Aging Clinical and Experimental Research. - : Springer Science and Business Media LLC. - 1594-0667 .- 1720-8319. ; 32:5, s. 861-868
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Tidskriftsartikel (refereegranskat)abstract
- MPI_AGE is a European Union co-funded research project aimed to use the Multidimensional Prognostic Index (MPI), a validated Comprehensive Geriatric Assessment (CGA)-based prognostic tool, to develop predictive rules that guide clinical and management decisions in older people in different European countries. A series of international studies performed in different settings have shown that the MPI is useful to predict mortality and risk of hospitalization in community-dwelling older subjects at population level. Furthermore, studies performed in older people who underwent a CGA before admission to a nursing home or receiving homecare services showed that the MPI successfully identified groups of persons who could benefit, in terms of reduced mortality, of specific therapies such as statins in diabetes mellitus and coronary artery disease, anticoagulants in atrial fibrillation and antidementia drugs in cognitive decline. A prospective trial carried out in nine hospitals in Europe and Australia demonstrated that the MPI was able to predict not only in-hospital and long-term mortality, but also institutionalization, re-hospitalization and receiving homecare services during the one-year follow-up after hospital discharge. The project also explored the association between MPI and mortality in hospitalized older patients in need of complex procedures such as transcatheter aortic valve implantation or enteral tube feeding. Evidence from these studies has prompted the MPI_AGE Investigators to formulate recommendations for healthcare providers, policy makers and the general population which may help to improve the cost-effectiveness of appropriate health care interventions for older patients.
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| 12. |
- Imarisio, Alberto, et al.
(författare)
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Plasma Cystatin C correlates with plasma NfL levels and predicts disease progression in Parkinson's disease.
- 2021
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Ingår i: Neuro-degenerative diseases. - : S. Karger AG. - 1660-2862 .- 1660-2854. ; 21, s. 109-116
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies reported increased plasma levels of Cystatin C (Cys-C) in Parkinson's disease (PD) and claimed for a possible association with disease severity and progression. The aim of this study was to evaluate plasma Cys-C in PD and healthy controls (HC) and test its association with markers of peripheral inflammation, neurodegeneration and clinical progression in a longitudinal study.Plasma Cys-C, high-sensitive C-reactive protein (hsCRP), interleukin 6 (IL-6) and Neurofilament Light Chain (NfL) were assessed at the baseline in 71 consecutive non-demented PD and 69 HC. PD patients underwent an extensive motor and cognitive assessment at baseline and after 2 years of follow-up. The association of Cys-C with disease severity was evaluated in a multilinear model adjusted for the effect of age, sex, disease duration and peripheral inflammation.Cys-C levels appeared to be higher in PD compared to controls and correlated with the plasma neuronal marker NfL (r = 0.204, p = 0.046). In longitudinal analyses, PD patients with higher Cys-C levels exhibited faster motor progression at two years of follow-up independently from the peripheral inflammatory profile.Cys-C was associated with higher NfL levels and a remarkably faster motor progression in PD independently from peripheral inflammation. Further studies are needed in order to understand the mechanisms underpinning the association of Cys-C with higher neuronal damage markers in neurodegenerative diseases.
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| 13. |
- Jones, Lesley, et al.
(författare)
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Convergent genetic and expression data implicate immunity in Alzheimer's disease
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671
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Tidskriftsartikel (refereegranskat)abstract
- Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
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| 14. |
- Lambert, Jean-Charles, et al.
(författare)
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The CALHM1 P86L Polymorphism is a Genetic Modifier of Age at Onset in Alzheimer's Disease : a Meta-Analysis Study
- 2010
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 22:1, s. 247-255
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Tidskriftsartikel (refereegranskat)abstract
- The only established genetic determinant of non-Mendelian forms of Alzheimer's disease (AD) is the epsilon 4 allele of the apolipoprotein E gene (APOE). Recently, it has been reported that the P86L polymorphism of the calcium homeostasis modulator 1 gene (CALHM1) is associated with the risk of developing AD. In order to independently assess this association, we performed a meta-analysis of 7,873 AD cases and 13,274 controls of Caucasian origin (from a total of 24 centers in Belgium, Finland, France, Italy, Spain, Sweden, the UK, and the USA). Our results indicate that the CALHM1 P86L polymorphism is likely not a genetic determinant of AD but may modulate age of onset by interacting with the effect of the epsilon 4 allele of the APOE gene.
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| 15. |
- Palmer, Katie, et al.
(författare)
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Association of polypharmacy and hyperpolypharmacy with frailty states : a systematic review and meta-analysis
- 2019
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Ingår i: European Geriatric Medicine. - : Springer Science and Business Media LLC. - 1878-7649 .- 1878-7657. ; 10:1, s. 9-36
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Forskningsöversikt (refereegranskat)abstract
- Purpose: To investigate: (1) the cross-sectional association between polypharmacy, hyperpolypharmacy and presence of prefrailty or frailty; (2) the risk of incident prefrailty or frailty in persons with polypharmacy, and vice versa.Methods: A systematic review and meta-analysis was performed according to PRISMA guidelines. We searched PubMed, Web of Science, and Embase from 01/01/1998 to 5/2/2018. Pooled estimates were obtained through random effect models and Mantel-Haenszel weighting. Homogeneity was assessed with the I-2 statistic and publication bias with Egger's and Begg's tests.Results: Thirty-seven studies were included. The pooled proportion of polypharmacy in persons with prefrailty and frailty was 47% (95% CI 33-61) and 59% (95% CI 42-76), respectively. Increased odds ratio of polypharmacy were seen for prefrail (pooled OR=1.52; 95% CI 1.32-1.79) and frail persons (pooled OR=2.62, 95% CI 1.81-3.79). Hyperpolypharmacy was also increased in prefrail (OR=1.95; 95% CI 1.41-2.70) and frail (OR=6.57; 95% CI 9.57-10.48) persons compared to robust persons. Only seven longitudinal studies reported data on the risk of either incident prefrailty or frailty in persons with baseline polypharmacy. A significant higher odds of developing prefrailty was found in robust persons with polypharmacy (pooled OR=1.30; 95% CI 1.12-1.51). We found no papers investigating polypharmacy incidence in persons with prefrailty/frailty.Conclusions: Polypharmacy is common in prefrail and frail persons, and these individuals are also more likely to be on extreme drug regimens, i.e. hyperpolypharmacy, than robust older persons. More research is needed to investigate the causal relationship between polypharmacy and frailty syndromes, thereby identifying ways to jointly reduce drug burden and prefrailty/frailty in these individuals.
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| 16. |
- Pilotto, Andrea, et al.
(författare)
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Differences Between Plasma and Cerebrospinal Fluid p-tau181 and p-tau231 in Early Alzheimer's Disease.
- 2022
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Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 87:3, s. 991-997
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Tidskriftsartikel (refereegranskat)abstract
- Plasma phosphorylated tau species have been recently proposed as peripheral markers of Alzheimer's disease (AD) pathology. In this cross-sectional study including 91 subjects, plasma and cerebrospinal fluid (CSF) p-tau181 and p-tau231 levels were elevated in the early symptomatic stages of AD. Plasma p-tau231 and p-tau181 were strongly related to CSF phosphorylated tau, total tau and amyloid and exhibited a high accuracy-close to CSF p-tau231 and p-tau181-to identify AD already in the early stage of the disease. The findings might support the use as diagnostic and prognostic peripheral AD biomarkers in both research and clinical settings.
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| 17. |
- Wormser, David, et al.
(författare)
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Adult height and the risk of cause-specific death and vascular morbidity in 1 million people : individual participant meta-analysis
- 2012
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 41:5, s. 1419-1433
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe extent to which adult height, a biomarker of the interplay of genetic endowment and early-life experiences, is related to risk of chronic diseases in adulthood is uncertain.MethodsWe calculated hazard ratios (HRs) for height, assessed in increments of 6.5 cm, using individual-participant data on 174 374 deaths or major non-fatal vascular outcomes recorded among 1 085 949 people in 121 prospective studies.ResultsFor people born between 1900 and 1960, mean adult height increased 0.5-1 cm with each successive decade of birth. After adjustment for age, sex, smoking and year of birth, HRs per 6.5 cm greater height were 0.97 (95% confidence interval: 0.96-0.99) for death from any cause, 0.94 (0.93-0.96) for death from vascular causes, 1.04 (1.03-1.06) for death from cancer and 0.92 (0.90-0.94) for death from other causes. Height was negatively associated with death from coronary disease, stroke subtypes, heart failure, stomach and oral cancers, chronic obstructive pulmonary disease, mental disorders, liver disease and external causes. In contrast, height was positively associated with death from ruptured aortic aneurysm, pulmonary embolism, melanoma and cancers of the pancreas, endocrine and nervous systems, ovary, breast, prostate, colorectum, blood and lung. HRs per 6.5 cm greater height ranged from 1.26 (1.12-1.42) for risk of melanoma death to 0.84 (0.80-0.89) for risk of death from chronic obstructive pulmonary disease. HRs were not appreciably altered after further adjustment for adiposity, blood pressure, lipids, inflammation biomarkers, diabetes mellitus, alcohol consumption or socio-economic indicators.ConclusionAdult height has directionally opposing relationships with risk of death from several different major causes of chronic diseases.
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