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
Main Authors: McGrath, Emer R., Himali, Jayandra J., Levy, Daniel, Conner, Sarah C., Pase, Matthew P., Abraham, Carmela R., Courchesne, Paul, Satizabal, Claudia L., Vasan, Ramachandran S., Beiser, Alexa S., Seshadri, Sudha
Format: Journal Article
Language:English
Published: United States Public Library of Science 04.03.2019
Public Library of Science (PLoS)
Subjects:
Adults
Advertising executives
Aged
Aging
Alzheimer Disease - blood
Alzheimer Disease - diagnosis
Alzheimer Disease - epidemiology
Alzheimer's disease
Analysis
Antihypertensives
Apolipoprotein E
Apolipoproteins
Biology and Life Sciences
Biomarkers
Biomarkers - blood
Blood Pressure
Brain
Cardiovascular diseases
Cognition
Cognition & reasoning
Cognitive ability
Dementia
Dementia - blood
Dementia - diagnosis
Dementia - epidemiology
Dementia disorders
Diabetes mellitus
Dialysis
Disease
Epidermal growth factor receptors
Female
Fibroblast Growth Factor-23
Fibroblast growth factors
Fibroblast Growth Factors - blood
Fibroblasts
Growth factors
Hazards
Health risk assessment
Health sciences
Heart
Humans
Incidence
Klotho protein
Longitudinal Studies
Magnetic resonance imaging
Male
Measurement methods
Medicine
Medicine and Health Sciences
Metabolism
Offspring
Older people
Physical sciences
Physiology
Population
Prospective Studies
Proteins
Public health
Regression analysis
Renal function
Risk
Risk Factors
Smoking
United States - epidemiology
Vascular diseases
Vitamin deficiency
United States
United States > US
ISSN:1932-6203, 1932-6203
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Summary: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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Competing Interests: The authors have declared that no competing interests exist.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0213321