Circulating fibroblast growth factor 23 levels and incident dementia: The Framingham heart study.

<h4>Background</h4>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.<h4>Objective</h4>...

Full description

Bibliographic Details
Main Authors: Emer R McGrath, Jayandra J Himali, Daniel Levy, Sarah C Conner, Matthew P Pase, Carmela R Abraham, Paul Courchesne, Claudia L Satizabal, Ramachandran S Vasan, Alexa S Beiser, Sudha Seshadri
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2019-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0213321
_version_ 1798032715768922112
author Emer R McGrath
Jayandra J Himali
Daniel Levy
Sarah C Conner
Matthew P Pase
Carmela R Abraham
Paul Courchesne
Claudia L Satizabal
Ramachandran S Vasan
Alexa S Beiser
Sudha Seshadri
author_facet Emer R McGrath
Jayandra J Himali
Daniel Levy
Sarah C Conner
Matthew P Pase
Carmela R Abraham
Paul Courchesne
Claudia L Satizabal
Ramachandran S Vasan
Alexa S Beiser
Sudha Seshadri
author_sort Emer R McGrath
collection DOAJ
description <h4>Background</h4>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.<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.
first_indexed 2024-04-11T20:18:15Z
format Article
id doaj.art-a50afaea5ab64c50b6c3e00afbed08c4
institution Directory Open Access Journal
issn 1932-6203
language English
last_indexed 2024-04-11T20:18:15Z
publishDate 2019-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj.art-a50afaea5ab64c50b6c3e00afbed08c42022-12-22T04:04:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01143e021332110.1371/journal.pone.0213321Circulating fibroblast growth factor 23 levels and incident dementia: The Framingham heart study.Emer R McGrathJayandra J HimaliDaniel LevySarah C ConnerMatthew P PaseCarmela R AbrahamPaul CourchesneClaudia L SatizabalRamachandran S VasanAlexa S BeiserSudha Seshadri<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.https://doi.org/10.1371/journal.pone.0213321
spellingShingle Emer R McGrath
Jayandra J Himali
Daniel Levy
Sarah C Conner
Matthew P Pase
Carmela R Abraham
Paul Courchesne
Claudia L Satizabal
Ramachandran S Vasan
Alexa S Beiser
Sudha Seshadri
Circulating fibroblast growth factor 23 levels and incident dementia: The Framingham heart study.
PLoS ONE
title Circulating fibroblast growth factor 23 levels and incident dementia: The Framingham heart study.
title_full Circulating fibroblast growth factor 23 levels and incident dementia: The Framingham heart study.
title_fullStr Circulating fibroblast growth factor 23 levels and incident dementia: The Framingham heart study.
title_full_unstemmed Circulating fibroblast growth factor 23 levels and incident dementia: The Framingham heart study.
title_short Circulating fibroblast growth factor 23 levels and incident dementia: The Framingham heart study.
title_sort circulating fibroblast growth factor 23 levels and incident dementia the framingham heart study
url https://doi.org/10.1371/journal.pone.0213321
work_keys_str_mv AT emerrmcgrath circulatingfibroblastgrowthfactor23levelsandincidentdementiatheframinghamheartstudy
AT jayandrajhimali circulatingfibroblastgrowthfactor23levelsandincidentdementiatheframinghamheartstudy
AT daniellevy circulatingfibroblastgrowthfactor23levelsandincidentdementiatheframinghamheartstudy
AT sarahcconner circulatingfibroblastgrowthfactor23levelsandincidentdementiatheframinghamheartstudy
AT matthewppase circulatingfibroblastgrowthfactor23levelsandincidentdementiatheframinghamheartstudy
AT carmelarabraham circulatingfibroblastgrowthfactor23levelsandincidentdementiatheframinghamheartstudy
AT paulcourchesne circulatingfibroblastgrowthfactor23levelsandincidentdementiatheframinghamheartstudy
AT claudialsatizabal circulatingfibroblastgrowthfactor23levelsandincidentdementiatheframinghamheartstudy
AT ramachandransvasan circulatingfibroblastgrowthfactor23levelsandincidentdementiatheframinghamheartstudy
AT alexasbeiser circulatingfibroblastgrowthfactor23levelsandincidentdementiatheframinghamheartstudy
AT sudhaseshadri circulatingfibroblastgrowthfactor23levelsandincidentdementiatheframinghamheartstudy