33 research outputs found
Longitudinal interplay between subclinical atherosclerosis, cardiovascular risk factors, and cerebral glucose metabolism in midlife: results from the PESA prospective cohort study.
BACKGROUND
Cardiovascular disease and dementia often coexist at advanced stages. Yet, longitudinal studies examining the interplay between atherosclerosis and its risk factors on brain health in midlife are scarce. We aimed to characterise the longitudinal associations between cerebral glucose metabolism, subclinical atherosclerosis, and cardiovascular risk factors in middle-aged asymptomatic individuals.
METHODS
The Progression of Early Subclinical Atherosclerosis (PESA) study is a Spanish longitudinal observational cohort study of 4184 asymptomatic individuals aged 40-54 years (NCT01410318). Participants with subclinical atherosclerosis underwent longitudinal cerebral [18F]fluorodeoxyglucose ([18F]FDG)-PET, and annual percentage change in [18F]FDG uptake was assessed (primary outcome). Cardiovascular risk was quantified with SCORE2 and subclinical atherosclerosis with three-dimensional vascular ultrasound (exposures). Multivariate regression and linear mixed effects models were used to assess associations between outcomes and exposures. Additionally, blood-based biomarkers of neuropathology were quantified and mediation analyses were performed. Secondary analyses were corrected for multiple comparisons using the false discovery rate (FDR) approach.
FINDINGS
This longitudinal study included a PESA subcohort of 370 participants (median age at baseline 49·8 years [IQR 46·1-52·2]; 309 [84%] men, 61 [16%] women; median follow-up 4·7 years [IQR 4·2-5·2]). Baseline scans took place between March 6, 2013, and Jan 21, 2015, and follow-up scans between Nov 24, 2017, and Aug 7, 2019. Persistent high risk of cardiovascular disease was associated with an accelerated decline of cortical [18F]FDG uptake compared with low risk (β=-0·008 [95% CI -0·013 to -0·002]; pFDR=0·040), with plasma neurofilament light chain, a marker of neurodegeneration, mediating this association by 20% (β=0·198 [0·008 to 0·740]; pFDR=0·050). Moreover, progression of subclinical carotid atherosclerosis was associated with an additional decline in [18F]FDG uptake in Alzheimer's disease brain regions, not explained by cardiovascular risk (β=-0·269 [95% CI -0·509 to -0·027]; p=0·029).
INTERPRETATION
Middle-aged asymptomatic individuals with persistent high risk of cardiovascular disease and subclinical carotid atherosclerosis already present brain metabolic decline, suggesting that maintenance of cardiovascular health during midlife could contribute to reductions in neurodegenerative disease burden later in life.
FUNDING
Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III, Santander Bank, Pro-CNIC Foundation, BrightFocus Foundation, BBVA Foundation, "la Caixa" Foundation.Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III, Santander Bank, Pro-CNIC
Foundation, BrightFocus Foundation, BBVA Foundation, “la Caixa” Foundation.
We thank the PESA participants and the imaging, administrative, and
medical PESA teams. The PESA study is equally co-funded by the
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)
and Santander Bank (Madrid, Spain) and also receives funding from the
Instituto de Salud Carlos III (ISCIII), Madrid, Spain (PI15/02019),
the European Regional Development Fund (ERDF—A Way to Build
Europe), and the European Social Fund (ESF—Investing in Your
Future). CNIC is a Severo Ochoa Center of Excellence (CEX2020-
001041-S) and is supported by the ISCIII, the Spanish Ministry for
Science and Innovation, and the Pro-CNIC Foundation. CT-P was
supported by a “la Caixa” Foundation fellowship (ID 100010434,
LCF/BQ/DI19/11730052). MC-C was supported by a Miguel Servet
type II research contract (ISCIII, CPII21/00007) and the Fondo de
Investigación Sanitaria (ISCIII, PI20/00819). We acknowledge the
Sephardic Foundation on Aging and other donors of the Alzheimer’s
Disease Research (grant number A2022034S), a programme of the
BrightFocus Foundation, for support of this research. This work was
also partially produced with the support of a 2021 Leonardo Grant for
Researchers and Cultural Creators from the BBVA Foundation awarded
to MC-C (the Foundation takes no responsibility for the opinions,
statements, and contents of this project, which are entirely the
responsibility of its authors). BI was supported by the European
Research Council (ERC-2018-CoG 819775-MATRIX). MS is supported
by the Knut and Alice Wallenberg Foundation (Wallenberg Centre for
Molecular and Translational Medicine; KAW2014.0363), the Swedish
Research Council (2017-02869, 2021-02678, 2021-06545), the Swedish
state under the agreement between the Swedish Government and the
County Councils, the ALF-agreement (ALFGBG-813971,
ALFGBG-965326), the Swedish Brain Foundation (FO2021-0311), and
the Swedish Alzheimer Foundation (AF-740191). MS-C receives
funding from the European Research Council (grant agreement
number 948677), project “PI19/00155”, funded by ISCIII and co-funded
by the EU, and a fellowship from “la Caixa” Foundation (ID 100010434)
and from the EU’s Horizon 2020 research and innovation programme
under the Marie Skłodowska-Curie grant agreement number 847648
(LCF/BQ/PR21/11840004). HZ is a Wallenberg Scholar supported by
grants from the Swedish Research Council (#2022-01018), the EU’s
Horizon Europe research and innovation programme under grant
agreement number 101053962, Swedish State Support for Clinical
Research (#ALFGBG-71320), the Alzheimer Drug Discovery
Foundation, USA (#201809-2016862), the AD Strategic Fund and the
Alzheimer’s Association (#ADSF-21-831376-C, #ADSF-21-831381-C,
#ADSF-21-831377-C), the Bluefield Project, the Olav Thon Foundation,
the Erling-Persson Family Foundation, Stiftelsen för Gamla
Tjänarinnor, Hjärnfonden, Sweden (#FO2022-0270), the EU’s Horizon
2020 research and innovation programme under the
Marie Skłodowska-Curie grant agreement number 860197 (MIRIADE),
the EU Joint Programme – Neurodegenerative Disease Research
(JPND2021-00694), and the UK Dementia Research Institute at UCL
(UKDRI-1003). KB is supported by the Swedish Research Council
(#2017-00915, #2022-00732), the Swedish state under the agreement
between the Swedish Government and the County Councils, the ALFagreement (#ALFGBG-715986, #ALFGBG-965240), the Swedish
Alzheimer Foundation (#AF-930351, #AF-939721, #AF-968270),
Hjärnfonden, Sweden (#FO2017-0243, #ALZ2022-0006), the
Alzheimer’s Association 2021 Zenith Award (ZEN-21-848495), and the
Alzheimer’s Association 2022–2025 grant (SG-23-1038904 QC).S
Longitudinal interplay between subclinical atherosclerosis, cardiovascular risk factors, and cerebral glucose metabolism in midlife: results from the PESA prospective cohort study
BACKGROUND: Cardiovascular disease and dementia often coexist at advanced stages. Yet, longitudinal studies examining the interplay between atherosclerosis and its risk factors on brain health in midlife are scarce. We aimed to characterise the longitudinal associations between cerebral glucose metabolism, subclinical atherosclerosis, and cardiovascular risk factors in middle-aged asymptomatic individuals. METHODS: The Progression of Early Subclinical Atherosclerosis (PESA) study is a Spanish longitudinal observational cohort study of 4184 asymptomatic individuals aged 40-54 years (NCT01410318). Participants with subclinical atherosclerosis underwent longitudinal cerebral [18F]fluorodeoxyglucose ([18F]FDG)-PET, and annual percentage change in [18F]FDG uptake was assessed (primary outcome). Cardiovascular risk was quantified with SCORE2 and subclinical atherosclerosis with three-dimensional vascular ultrasound (exposures). Multivariate regression and linear mixed effects models were used to assess associations between outcomes and exposures. Additionally, blood-based biomarkers of neuropathology were quantified and mediation analyses were performed. Secondary analyses were corrected for multiple comparisons using the false discovery rate (FDR) approach. FINDINGS: This longitudinal study included a PESA subcohort of 370 participants (median age at baseline 49·8 years [IQR 46·1-52·2]; 309 [84%] men, 61 [16%] women; median follow-up 4·7 years [IQR 4·2-5·2]). Baseline scans took place between March 6, 2013, and Jan 21, 2015, and follow-up scans between Nov 24, 2017, and Aug 7, 2019. Persistent high risk of cardiovascular disease was associated with an accelerated decline of cortical [18F]FDG uptake compared with low risk (β=-0·008 [95% CI -0·013 to -0·002]; pFDR=0·040), with plasma neurofilament light chain, a marker of neurodegeneration, mediating this association by 20% (β=0·198 [0·008 to 0·740]; pFDR=0·050). Moreover, progression of subclinical carotid atherosclerosis was associated with an additional decline in [18F]FDG uptake in Alzheimer's disease brain regions, not explained by cardiovascular risk (β=-0·269 [95% CI -0·509 to -0·027]; p=0·029). INTERPRETATION: Middle-aged asymptomatic individuals with persistent high risk of cardiovascular disease and subclinical carotid atherosclerosis already present brain metabolic decline, suggesting that maintenance of cardiovascular health during midlife could contribute to reductions in neurodegenerative disease burden later in life. FUNDING: Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III, Santander Bank, Pro-CNIC Foundation, BrightFocus Foundation, BBVA Foundation, "la Caixa" Foundation
The James Webb Space Telescope Mission
Twenty-six years ago a small committee report, building on earlier studies,
expounded a compelling and poetic vision for the future of astronomy, calling
for an infrared-optimized space telescope with an aperture of at least .
With the support of their governments in the US, Europe, and Canada, 20,000
people realized that vision as the James Webb Space Telescope. A
generation of astronomers will celebrate their accomplishments for the life of
the mission, potentially as long as 20 years, and beyond. This report and the
scientific discoveries that follow are extended thank-you notes to the 20,000
team members. The telescope is working perfectly, with much better image
quality than expected. In this and accompanying papers, we give a brief
history, describe the observatory, outline its objectives and current observing
program, and discuss the inventions and people who made it possible. We cite
detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space
Telescope Overview, 29 pages, 4 figure
Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries
Abstract
Background
Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres.
Methods
This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries.
Results
In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia.
Conclusion
This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries