Send to

Choose Destination
J Intern Med. 2017 Jul;282(1):94-101. doi: 10.1111/joim.12621. Epub 2017 May 4.

Biomarkers of microvascular endothelial dysfunction predict incident dementia: a population-based prospective study.

Author information

Department of Clinical Sciences, Malmö, Faculty of Medicine, Lund University, Malmö, Sweden.
Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden.
Clinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Malmö, Sweden.
Institute of Cardiology, "G. d'Annunzio" University, Chieti, Italy.
Department of Neuroscience and Imaging, Institute for Advanced Biomedical Technologies, "G. d'Annunzio" University, Chieti, Italy.
Department of Cardiology, Skåne University Hospital, Malmö, Sweden.



Cerebral endothelial dysfunction occurs in a spectrum of neurodegenerative diseases. Whether biomarkers of microvascular endothelial dysfunction can predict dementia is largely unknown. We explored the longitudinal association of midregional pro-atrial natriuretic peptide (MR-proANP), C-terminal endothelin-1 (CT-proET-1) and midregional proadrenomedullin (MR-proADM) with dementia and subtypes amongst community-dwelling older adults.


A population-based cohort of 5347 individuals (men, 70%; age, 69 ± 6 years) without prevalent dementia provided plasma for determination of MR-proANP, CT-proET-1 and MR-proADM. Three-hundred-and-seventy-three patients (7%) were diagnosed with dementia (120 Alzheimer's disease, 83 vascular, 102 mixed, and 68 other aetiology) over a period of 4.6 ± 1.3 years. Relations between baseline biomarker plasma concentrations and incident dementia were assessed using multivariable Cox regression analysis.


Higher levels of MR-proANP were significantly associated with increased risk of all-cause and vascular dementia (hazard ratio [HR] per 1 SD: 1.20, 95% confidence interval [CI], 1.07-1.36; P = 0.002, and 1.52; 1.21-1.89; P < 0.001, respectively). Risk of all-cause dementia increased across the quartiles of MR-proANP (p for linear trend = 0.004; Q4, 145-1681 pmol L-1 vs. Q1, 22-77 pmol L-1 : HR: 1.83; 95%CI: 1.23-2.71) and was most pronounced for vascular type (p for linear trend = 0.005: HR: 2.71; 95%CI: 1.14-6.46). Moreover, the two highest quartiles of CT-proET-1 predicted vascular dementia with a cut-off value at 68 pmol L-1 (Q3-Q4, 68-432 pmol L-1 vs. Q1-Q2,4-68 pmol L-1 ; HR: 1.94; 95%CI: 1.12-3.36). Elevated levels of MR-proADM indicated no increased risk of developing dementia after adjustment for traditional risk factors.


Elevated plasma concentration of MR-proANP is an independent predictor of all-cause and vascular dementia. Pronounced increase in CT-proET-1 indicates higher risk of vascular dementia.


adrenomedullin; atrial natriuretic peptide; biomarkers; dementia; endothelial dysfunction; endothelin

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center