The N-terminal pro B-type natriuretic peptide, and risk of dementia and cognitive decline: a 10-year follow-up study in the general population.
BACKGROUND
The N-terminal pro B-type natriuretic peptide (NT-proBNP) has a well-documented prognostic value for cardiovascular disease (CVD) and higher levels are associated with cognitive-dysfunction in patients with CVD. However, how NT-proBNP relates to incident dementia and cognitive-decline in community-dwelling persons is unknown.


METHODS
Between 1997 and 2001, serum NT-proBNP was measured in 6040 participants (mean age 69 years, 57% women) free of heart-failure and dementia from the Rotterdam Study. Participants were continuously followed-up for incident dementia until 2012, for 56,616 person-years. Cognition was assessed at baseline and reassessed between 2002 and 2006 by Letter-Digit-Substitution-task, Stroop test and Word-Fluency test. Associations of NT-proBNP with dementia (555 cases), Alzheimer's disease (357 cases) and vascular dementia (32 cases) were assessed linearly, and in quartiles using Cox regression. Associations of NT-proBNP with cognitive-decline were assessed using multiple linear regression. All analyses were repeated after excluding patients with CVD.


RESULTS
Higher NT-proBNP was associated with a higher risk of dementia, even after excluding patients with CVD and adjusting for cardiovascular risk factors, HR per SD 1.27 (95% CI 1.13 to 1.44). Associations were particularly strong for vascular dementia, HR per SD 2.04 (95% CI 1.18 to 3.55), but also for Alzheimer's disease when comparing the second and third quartile with first. Higher NT-proBNP was cross-sectionally associated with poorer performance in multiple cognitive tests but longitudinally only in Letter-Digit-Substitution-task.


CONCLUSIONS
NT-proBNP reflecting subclinical CVD is associated with dementia, particularly vascular dementia. NT-proBNP can be a useful marker of imminent cognitive-decline and dementia in absence of clinical CVD.
Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Saira Saeed
SS
Mirza
Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands.
Renée F A G
RF
de Bruijn
Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands.
Peter J
PJ
Koudstaal
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Anton H
AH
van den Meiracker
Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Oscar H
OH
Franco
Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Albert
A
Hofman
Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands Department of Department of Child and Adolescent Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands Department of Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands.
Henning
H
Tiemeier
Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands.
M Arfan
MA
Ikram
D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics / Q000523:psychology; D015415:Biomarkers / Q000032:analysis; D002318:Cardiovascular Diseases / Q000150:complications; D003072:Cognition Disorders / Q000175:diagnosis* / Q000235:genetics / Q000523:psychology; D003430:Cross-Sectional Studies; D003704:Dementia / Q000175:diagnosis* / Q000235:genetics / Q000523:psychology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000032:analysis* / Q000235:genetics; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000032:analysis* / Q000235:genetics; D011379:Prognosis; D012307:Risk Factors; D012959:Socioeconomic Factors
D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
ALZHEIMER'S DISEASE; DEMENTIA; EPIDEMIOLOGY