Brain-derived neurotrophic factor predicts mortality risk in older women.

OBJECTIVES: To test the hypothesis that low circulating brain-derived neurotrophic factor (BDNF), a secretory member of the neurotrophin family that has a protective role in neurodegeneration and stress responses and a regulatory role in metabolism, predicts risk of all-cause mortality in 85-year-old men and women. DESIGN: Longitudinal study with 50- to 58-month follow-up. SETTING: The 1914 cohort, a population-based cohort established in 1964 by the Research Center for Prevention and Health at Glostrup Hospital. PARTICIPANTS: One hundred eighty-eight unselected 85-year-old Danes. MEASUREMENTS: BDNF was measured in plasma and serum. The Danish National Register of Patients was used to collect data on morbidity. The primary outcome in Cox regression analyses was all-cause mortality. RESULTS: Women with low plasma BDNF (lowest tertile) had greater all-cause mortality risk than women with high plasma BDNF (highest tertile) (hazard ratio=2.2, 95% confidence interval=1.1-4.7). Low plasma BDNF predicted mortality independently of activities of daily living; education; and a history of central nervous system disease, cerebrovascular accidents, cardiovascular disease, cancer, respiratory disease, and low-grade inflammation. No association was found between plasma BDNF and mortality in men, and serum BDNF did not influence mortality in either sex. CONCLUSION: Low plasma BDNF is a novel, independent, and robust biomarker of mortality risk in old women. BDNF may be a central factor in the network of multimorbidity in old populations.