NT‐proBNP and Risk of Dementia in a General Japanese Elderly Population: The Hisayama Study

BACKGROUND: Epidemiological evidence implies a link between heart disease and dementia. However, few prospective studies have assessed the association between serum NT‐proBNP (N‐terminal pro–B‐type natriuretic peptide) levels and dementia. METHODS AND RESULTS: A total of 1635 community‐dwelling Japanese elderly aged ≥60 years without dementia (57% women, mean age±SD 70.8±7.7 years) were followed up for 10 years. Serum NT‐proBNP levels were divided into 4 categories (≤54, 55‐124, 125‐299, and ≥300 pg/mL). The hazard ratios were estimated using a Cox proportional hazards model. During the follow‐up period, 377 subjects developed all‐cause dementia, 247 Alzheimer disease, and 102 vascular dementia. The age‐ and sex‐adjusted incidence of all‐cause dementia was 31.5 per 1000 person‐years and increased significantly with higher serum NT‐proBNP levels, being 16.4, 32.0, 35.7, and 45.5, respectively (P for trend <0.01). Subjects with serum NT‐proBNP levels of ≥300 pg/mL had a significantly higher risk of all‐cause dementia (hazard ratio=2.46, 95% CI 1.63‐3.71) than those with serum NT‐proBNP levels of ≤54 pg/mL after adjusting for confounders. Similar risks were observed for Alzheimer disease and vascular dementia. Incorporation of the serum NT‐proBNP level into a model with known risk factors for dementia significantly improved the predictive ability for incident dementia (c‐statistics 0.780‐0.787, P=0.02; net reclassification improvement 0.189, P=0.001; integrated discrimination improvement 0.011, P=0.003). CONCLUSIONS: Higher serum NT‐proBNP levels were significantly associated with an increased risk of dementia. Serum NT‐proBNP could be a novel biomarker for predicting future risk of dementia in the general elderly population.