Circulating fibroblast growth factor 23 levels and incident dementia: The Framingham heart study
Fibroblast growth factor 23 is an emerging vascular biomarker, recently associated with cerebral small vessel disease and poor cognition in patients on dialysis. It also interacts with klotho, an anti-aging and cognition enhancing protein. To determine if circulating Fibroblast growth factor 23 (FGF...
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| Published in: | PloS one Vol. 14; no. 3; p. e0213321 |
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| Main Authors: | , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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Public Library of Science
04.03.2019
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| ISSN: | 1932-6203, 1932-6203 |
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| Abstract | Fibroblast growth factor 23 is an emerging vascular biomarker, recently associated with cerebral small vessel disease and poor cognition in patients on dialysis. It also interacts with klotho, an anti-aging and cognition enhancing protein.
To determine if circulating Fibroblast growth factor 23 (FGF23) is associated with new-onset cognitive outcomes in a community-based cohort of cognitively healthy adults with long-term follow-up.
We measured serum FGF23 levels in 1537 [53% women, mean age 68.7 (SD 5.7)] dementia-free Framingham Offspring participants at their 7th quadrennial examination (1998-2001), and followed these participants for the development of clinical all-cause dementia and Alzheimer's disease (AD). Secondary outcomes included MRI-based structural brain measures, and neurocognitive test performance at exam 7.
During a median (Q1, Q3) 12-year (7.0, 13.3) follow up, 122 (7.9%) participants developed dementia, of whom 91 (5.9%) had AD. Proportional-hazards regression analysis, adjusted for age, sex, education, systolic blood pressure, antihypertensive medication, prevalent cardiovascular disease, diabetes mellitus, smoking status and apoE ε4 carrier status, revealed that higher serum FGF23 levels were associated with an increased risk of incident dementia and AD (Hazard ratio [HR] per 1 standard deviation increment in inverse transformed FGF23 level 1.25, 95% CI 1.02-1.53, and 1.32, 95% CI 1.04-1.69, respectively). There was no significant interaction according to presence/absence of significant renal impairment (eGFR <30 versus ≥30ml/min) and risk of dementia (based on 1537; p = 0.97).
Higher circulating FGF23 is associated with an increased risk of dementia, suggesting that FGF23-related biological pathways may play a role in the development of dementia. |
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| AbstractList | Fibroblast growth factor 23 is an emerging vascular biomarker, recently associated with cerebral small vessel disease and poor cognition in patients on dialysis. It also interacts with klotho, an anti-aging and cognition enhancing protein.
To determine if circulating Fibroblast growth factor 23 (FGF23) is associated with new-onset cognitive outcomes in a community-based cohort of cognitively healthy adults with long-term follow-up.
We measured serum FGF23 levels in 1537 [53% women, mean age 68.7 (SD 5.7)] dementia-free Framingham Offspring participants at their 7th quadrennial examination (1998-2001), and followed these participants for the development of clinical all-cause dementia and Alzheimer's disease (AD). Secondary outcomes included MRI-based structural brain measures, and neurocognitive test performance at exam 7.
During a median (Q1, Q3) 12-year (7.0, 13.3) follow up, 122 (7.9%) participants developed dementia, of whom 91 (5.9%) had AD. Proportional-hazards regression analysis, adjusted for age, sex, education, systolic blood pressure, antihypertensive medication, prevalent cardiovascular disease, diabetes mellitus, smoking status and apoE ε4 carrier status, revealed that higher serum FGF23 levels were associated with an increased risk of incident dementia and AD (Hazard ratio [HR] per 1 standard deviation increment in inverse transformed FGF23 level 1.25, 95% CI 1.02-1.53, and 1.32, 95% CI 1.04-1.69, respectively). There was no significant interaction according to presence/absence of significant renal impairment (eGFR <30 versus ≥30ml/min) and risk of dementia (based on 1537; p = 0.97).
Higher circulating FGF23 is associated with an increased risk of dementia, suggesting that FGF23-related biological pathways may play a role in the development of dementia. Fibroblast growth factor 23 is an emerging vascular biomarker, recently associated with cerebral small vessel disease and poor cognition in patients on dialysis. It also interacts with klotho, an anti-aging and cognition enhancing protein. To determine if circulating Fibroblast growth factor 23 (FGF23) is associated with new-onset cognitive outcomes in a community-based cohort of cognitively healthy adults with long-term follow-up. We measured serum FGF23 levels in 1537 [53% women, mean age 68.7 (SD 5.7)] dementia-free Framingham Offspring participants at their 7.sup.th quadrennial examination (1998-2001), and followed these participants for the development of clinical all-cause dementia and Alzheimer's disease (AD). Secondary outcomes included MRI-based structural brain measures, and neurocognitive test performance at exam 7. During a median (Q1, Q3) 12-year (7.0, 13.3) follow up, 122 (7.9%) participants developed dementia, of whom 91 (5.9%) had AD. Proportional-hazards regression analysis, adjusted for age, sex, education, systolic blood pressure, antihypertensive medication, prevalent cardiovascular disease, diabetes mellitus, smoking status and apoE [epsilon]4 carrier status, revealed that higher serum FGF23 levels were associated with an increased risk of incident dementia and AD (Hazard ratio [HR] per 1 standard deviation increment in inverse transformed FGF23 level 1.25, 95% CI 1.02-1.53, and 1.32, 95% CI 1.04-1.69, respectively). There was no significant interaction according to presence/absence of significant renal impairment (eGFR <30 versus [greater than or equal to]30ml/min) and risk of dementia (based on 1537; p = 0.97). Higher circulating FGF23 is associated with an increased risk of dementia, suggesting that FGF23-related biological pathways may play a role in the development of dementia. Background Fibroblast growth factor 23 is an emerging vascular biomarker, recently associated with cerebral small vessel disease and poor cognition in patients on dialysis. It also interacts with klotho, an anti-aging and cognition enhancing protein. Objective To determine if circulating Fibroblast growth factor 23 (FGF23) is associated with new-onset cognitive outcomes in a community-based cohort of cognitively healthy adults with long-term follow-up. Methods We measured serum FGF23 levels in 1537 [53% women, mean age 68.7 (SD 5.7)] dementia-free Framingham Offspring participants at their 7.sup.th quadrennial examination (1998-2001), and followed these participants for the development of clinical all-cause dementia and Alzheimer's disease (AD). Secondary outcomes included MRI-based structural brain measures, and neurocognitive test performance at exam 7. Results During a median (Q1, Q3) 12-year (7.0, 13.3) follow up, 122 (7.9%) participants developed dementia, of whom 91 (5.9%) had AD. Proportional-hazards regression analysis, adjusted for age, sex, education, systolic blood pressure, antihypertensive medication, prevalent cardiovascular disease, diabetes mellitus, smoking status and apoE [epsilon]4 carrier status, revealed that higher serum FGF23 levels were associated with an increased risk of incident dementia and AD (Hazard ratio [HR] per 1 standard deviation increment in inverse transformed FGF23 level 1.25, 95% CI 1.02-1.53, and 1.32, 95% CI 1.04-1.69, respectively). There was no significant interaction according to presence/absence of significant renal impairment (eGFR <30 versus [greater than or equal to]30ml/min) and risk of dementia (based on 1537; p = 0.97). Conclusions Higher circulating FGF23 is associated with an increased risk of dementia, suggesting that FGF23-related biological pathways may play a role in the development of dementia. Background Fibroblast growth factor 23 is an emerging vascular biomarker, recently associated with cerebral small vessel disease and poor cognition in patients on dialysis. It also interacts with klotho, an anti-aging and cognition enhancing protein. Objective To determine if circulating Fibroblast growth factor 23 (FGF23) is associated with new-onset cognitive outcomes in a community-based cohort of cognitively healthy adults with long-term follow-up. Methods We measured serum FGF23 levels in 1537 [53% women, mean age 68.7 (SD 5.7)] dementia-free Framingham Offspring participants at their 7th quadrennial examination (1998–2001), and followed these participants for the development of clinical all-cause dementia and Alzheimer’s disease (AD). Secondary outcomes included MRI-based structural brain measures, and neurocognitive test performance at exam 7. Results During a median (Q1, Q3) 12-year (7.0, 13.3) follow up, 122 (7.9%) participants developed dementia, of whom 91 (5.9%) had AD. Proportional-hazards regression analysis, adjusted for age, sex, education, systolic blood pressure, antihypertensive medication, prevalent cardiovascular disease, diabetes mellitus, smoking status and apoE ε4 carrier status, revealed that higher serum FGF23 levels were associated with an increased risk of incident dementia and AD (Hazard ratio [HR] per 1 standard deviation increment in inverse transformed FGF23 level 1.25, 95% CI 1.02–1.53, and 1.32, 95% CI 1.04–1.69, respectively). There was no significant interaction according to presence/absence of significant renal impairment (eGFR <30 versus ≥30ml/min) and risk of dementia (based on 1537; p = 0.97). Conclusions Higher circulating FGF23 is associated with an increased risk of dementia, suggesting that FGF23-related biological pathways may play a role in the development of dementia. Fibroblast growth factor 23 is an emerging vascular biomarker, recently associated with cerebral small vessel disease and poor cognition in patients on dialysis. It also interacts with klotho, an anti-aging and cognition enhancing protein.BACKGROUNDFibroblast growth factor 23 is an emerging vascular biomarker, recently associated with cerebral small vessel disease and poor cognition in patients on dialysis. It also interacts with klotho, an anti-aging and cognition enhancing protein.To determine if circulating Fibroblast growth factor 23 (FGF23) is associated with new-onset cognitive outcomes in a community-based cohort of cognitively healthy adults with long-term follow-up.OBJECTIVETo determine if circulating Fibroblast growth factor 23 (FGF23) is associated with new-onset cognitive outcomes in a community-based cohort of cognitively healthy adults with long-term follow-up.We measured serum FGF23 levels in 1537 [53% women, mean age 68.7 (SD 5.7)] dementia-free Framingham Offspring participants at their 7th quadrennial examination (1998-2001), and followed these participants for the development of clinical all-cause dementia and Alzheimer's disease (AD). Secondary outcomes included MRI-based structural brain measures, and neurocognitive test performance at exam 7.METHODSWe measured serum FGF23 levels in 1537 [53% women, mean age 68.7 (SD 5.7)] dementia-free Framingham Offspring participants at their 7th quadrennial examination (1998-2001), and followed these participants for the development of clinical all-cause dementia and Alzheimer's disease (AD). Secondary outcomes included MRI-based structural brain measures, and neurocognitive test performance at exam 7.During a median (Q1, Q3) 12-year (7.0, 13.3) follow up, 122 (7.9%) participants developed dementia, of whom 91 (5.9%) had AD. Proportional-hazards regression analysis, adjusted for age, sex, education, systolic blood pressure, antihypertensive medication, prevalent cardiovascular disease, diabetes mellitus, smoking status and apoE ε4 carrier status, revealed that higher serum FGF23 levels were associated with an increased risk of incident dementia and AD (Hazard ratio [HR] per 1 standard deviation increment in inverse transformed FGF23 level 1.25, 95% CI 1.02-1.53, and 1.32, 95% CI 1.04-1.69, respectively). There was no significant interaction according to presence/absence of significant renal impairment (eGFR <30 versus ≥30ml/min) and risk of dementia (based on 1537; p = 0.97).RESULTSDuring a median (Q1, Q3) 12-year (7.0, 13.3) follow up, 122 (7.9%) participants developed dementia, of whom 91 (5.9%) had AD. Proportional-hazards regression analysis, adjusted for age, sex, education, systolic blood pressure, antihypertensive medication, prevalent cardiovascular disease, diabetes mellitus, smoking status and apoE ε4 carrier status, revealed that higher serum FGF23 levels were associated with an increased risk of incident dementia and AD (Hazard ratio [HR] per 1 standard deviation increment in inverse transformed FGF23 level 1.25, 95% CI 1.02-1.53, and 1.32, 95% CI 1.04-1.69, respectively). There was no significant interaction according to presence/absence of significant renal impairment (eGFR <30 versus ≥30ml/min) and risk of dementia (based on 1537; p = 0.97).Higher circulating FGF23 is associated with an increased risk of dementia, suggesting that FGF23-related biological pathways may play a role in the development of dementia.CONCLUSIONSHigher circulating FGF23 is associated with an increased risk of dementia, suggesting that FGF23-related biological pathways may play a role in the development of dementia. BackgroundFibroblast growth factor 23 is an emerging vascular biomarker, recently associated with cerebral small vessel disease and poor cognition in patients on dialysis. It also interacts with klotho, an anti-aging and cognition enhancing protein.ObjectiveTo determine if circulating Fibroblast growth factor 23 (FGF23) is associated with new-onset cognitive outcomes in a community-based cohort of cognitively healthy adults with long-term follow-up.MethodsWe measured serum FGF23 levels in 1537 [53% women, mean age 68.7 (SD 5.7)] dementia-free Framingham Offspring participants at their 7th quadrennial examination (1998-2001), and followed these participants for the development of clinical all-cause dementia and Alzheimer's disease (AD). Secondary outcomes included MRI-based structural brain measures, and neurocognitive test performance at exam 7.ResultsDuring a median (Q1, Q3) 12-year (7.0, 13.3) follow up, 122 (7.9%) participants developed dementia, of whom 91 (5.9%) had AD. Proportional-hazards regression analysis, adjusted for age, sex, education, systolic blood pressure, antihypertensive medication, prevalent cardiovascular disease, diabetes mellitus, smoking status and apoE ε4 carrier status, revealed that higher serum FGF23 levels were associated with an increased risk of incident dementia and AD (Hazard ratio [HR] per 1 standard deviation increment in inverse transformed FGF23 level 1.25, 95% CI 1.02-1.53, and 1.32, 95% CI 1.04-1.69, respectively). There was no significant interaction according to presence/absence of significant renal impairment (eGFR <30 versus ≥30ml/min) and risk of dementia (based on 1537; p = 0.97).ConclusionsHigher circulating FGF23 is associated with an increased risk of dementia, suggesting that FGF23-related biological pathways may play a role in the development of dementia. Background Fibroblast growth factor 23 is an emerging vascular biomarker, recently associated with cerebral small vessel disease and poor cognition in patients on dialysis. It also interacts with klotho, an anti-aging and cognition enhancing protein. Objective To determine if circulating Fibroblast growth factor 23 (FGF23) is associated with new-onset cognitive outcomes in a community-based cohort of cognitively healthy adults with long-term follow-up. Methods We measured serum FGF23 levels in 1537 [53% women, mean age 68.7 (SD 5.7)] dementia-free Framingham Offspring participants at their 7th quadrennial examination (1998–2001), and followed these participants for the development of clinical all-cause dementia and Alzheimer’s disease (AD). Secondary outcomes included MRI-based structural brain measures, and neurocognitive test performance at exam 7. Results During a median (Q1, Q3) 12-year (7.0, 13.3) follow up, 122 (7.9%) participants developed dementia, of whom 91 (5.9%) had AD. Proportional-hazards regression analysis, adjusted for age, sex, education, systolic blood pressure, antihypertensive medication, prevalent cardiovascular disease, diabetes mellitus, smoking status and apoE ε4 carrier status, revealed that higher serum FGF23 levels were associated with an increased risk of incident dementia and AD (Hazard ratio [HR] per 1 standard deviation increment in inverse transformed FGF23 level 1.25, 95% CI 1.02–1.53, and 1.32, 95% CI 1.04–1.69, respectively). There was no significant interaction according to presence/absence of significant renal impairment (eGFR <30 versus ≥30ml/min) and risk of dementia (based on 1537; p = 0.97). Conclusions Higher circulating FGF23 is associated with an increased risk of dementia, suggesting that FGF23-related biological pathways may play a role in the development of dementia. |
| Audience | Academic |
| Author | Himali, Jayandra J. Vasan, Ramachandran S. Courchesne, Paul Abraham, Carmela R. Levy, Daniel Pase, Matthew P. McGrath, Emer R. Seshadri, Sudha Conner, Sarah C. Satizabal, Claudia L. Beiser, Alexa S. |
| AuthorAffiliation | 4 Boston University School of Public Health, Boston, MA, United States of America 5 Boston University School of Medicine, Boston, MA, United States of America 1 Department of Neurology, Brigham & Women’s Hospital, Boston, MA, United States of America 8 Glenn Biggs Institute for Alzheimer’s & Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, TX, United States of America 3 Framingham Heart Study, Framingham, MA, United States of America 6 Population Sciences Branch, National Heart, Lung and Blood Institutes of Health, Bethesda, MD, United States of America Nathan S Kline Institute, UNITED STATES 2 Harvard Medical School, Boston, MA, United States of America 7 Melbourne Dementia Research Centre, The Florey Institute for Neuroscience and Mental Health, Victoria, Australia |
| AuthorAffiliation_xml | – name: 4 Boston University School of Public Health, Boston, MA, United States of America – name: 2 Harvard Medical School, Boston, MA, United States of America – name: 5 Boston University School of Medicine, Boston, MA, United States of America – name: 7 Melbourne Dementia Research Centre, The Florey Institute for Neuroscience and Mental Health, Victoria, Australia – name: 3 Framingham Heart Study, Framingham, MA, United States of America – name: 8 Glenn Biggs Institute for Alzheimer’s & Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, TX, United States of America – name: Nathan S Kline Institute, UNITED STATES – name: 1 Department of Neurology, Brigham & Women’s Hospital, Boston, MA, United States of America – name: 6 Population Sciences Branch, National Heart, Lung and Blood Institutes of Health, Bethesda, MD, United States of America |
| Author_xml | – sequence: 1 givenname: Emer R. orcidid: 0000-0002-3589-2964 surname: McGrath fullname: McGrath, Emer R. – sequence: 2 givenname: Jayandra J. surname: Himali fullname: Himali, Jayandra J. – sequence: 3 givenname: Daniel surname: Levy fullname: Levy, Daniel – sequence: 4 givenname: Sarah C. surname: Conner fullname: Conner, Sarah C. – sequence: 5 givenname: Matthew P. surname: Pase fullname: Pase, Matthew P. – sequence: 6 givenname: Carmela R. surname: Abraham fullname: Abraham, Carmela R. – sequence: 7 givenname: Paul surname: Courchesne fullname: Courchesne, Paul – sequence: 8 givenname: Claudia L. orcidid: 0000-0002-1115-4430 surname: Satizabal fullname: Satizabal, Claudia L. – sequence: 9 givenname: Ramachandran S. surname: Vasan fullname: Vasan, Ramachandran S. – sequence: 10 givenname: Alexa S. surname: Beiser fullname: Beiser, Alexa S. – sequence: 11 givenname: Sudha surname: Seshadri fullname: Seshadri, Sudha |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/30830941$$D View this record in MEDLINE/PubMed |
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| ContentType | Journal Article |
| Copyright | COPYRIGHT 2019 Public Library of Science 2019 McGrath et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 2019 McGrath et al 2019 McGrath et al |
| Copyright_xml | – notice: COPYRIGHT 2019 Public Library of Science – notice: 2019 McGrath et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. – notice: 2019 McGrath et al 2019 McGrath et al |
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| DOI | 10.1371/journal.pone.0213321 |
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Design and preliminary data publication-title: Preventive Medicine doi: 10.1016/0091-7435(75)90037-7 – volume: 143 start-page: 29 issue: 1 year: 1982 ident: ref15 article-title: The meaning and use of the area under a receiver operating characteristic (ROC) curve publication-title: Radiology doi: 10.1148/radiology.143.1.7063747 – volume: 174 start-page: 364 issue: 3 year: 2011 ident: ref17 article-title: Evaluating the incremental value of new biomarkers with integrated discrimination improvement publication-title: Am J Epidemiol doi: 10.1093/aje/kwr086 – volume: 75 start-page: 503 year: 2013 ident: ref31 article-title: Fibroblast growth factor 23 and Klotho: physiology and pathophysiology of an endocrine network of mineral metabolism publication-title: Annual review of physiology doi: 10.1146/annurev-physiol-030212-183727 – volume: 82 start-page: 1700 issue: 19 year: 2014 ident: ref3 article-title: Plasma FGF23 and the risk of stroke: the Northern Manhattan Study (NOMAS) publication-title: Neurology doi: 10.1212/WNL.0000000000000410 – volume: 5 issue: 7 year: 2016 ident: ref19 article-title: Plasma Fibroblast Growth Factor 23: Clinical Correlates and Association With Cardiovascular Disease and Mortality in the Framingham Heart Study publication-title: Journal of the American Heart Association doi: 10.1161/JAHA.116.003486 – volume: 7 start-page: 1065 issue: 4 year: 2014 ident: ref27 article-title: Life extension factor klotho enhances cognition publication-title: Cell reports doi: 10.1016/j.celrep.2014.03.076 – volume: 16 start-page: 274 issue: 2 year: 1992 ident: ref13 article-title: Method for quantification of brain, ventricular, and subarachnoid CSF volumes from MR images publication-title: Journal of computer assisted tomography doi: 10.1097/00004728-199203000-00018 – volume: 63 start-page: 1591 issue: 9 year: 2004 ident: ref12 article-title: Stroke risk profile, brain volume, and cognitive function The Framingham Offspring Study publication-title: Neurology doi: 10.1212/01.WNL.0000142968.22691.70 – volume: 18 start-page: 78 issue: 1 year: 2014 ident: ref5 article-title: FGF-23 and cognitive performance in hemodialysis patients publication-title: Hemodialysis international International Symposium on Home Hemodialysis doi: 10.1111/hdi.12100 – volume: 30 start-page: 529 issue: 3 year: 1999 ident: ref11 article-title: Predictors of brain morphology for the men of the NHLBI twin study publication-title: Stroke doi: 10.1161/01.STR.30.3.529 |
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