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Research paper
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
  1. Saira Saeed Mirza1,
  2. Renée F A G de Bruijn1,2,
  3. Peter J Koudstaal2,
  4. Anton H van den Meiracker3,
  5. Oscar H Franco1,
  6. Albert Hofman1,
  7. Henning Tiemeier1,4,5,
  8. M Arfan Ikram1,2,6
  1. 1Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
  2. 2Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands
  3. 3Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
  4. 4Department of Department of Child and Adolescent Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands
  5. 5Department of Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands
  6. 6Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands
  1. Correspondence to Dr M Arfan Ikram, Department of Epidemiology, Erasmus University Medical Center, PO Box 2040, Rotterdam 3000 CA, The Netherlands; m.a.ikram{at}


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.


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