Neuroprotective Biomarkers and Cognitive Function in a Long-Term Prospective Population-based Study of Aging US Adults

Adam J. Paulsen, Carla R. Schubert, Alex Pinto, Cynthia M. Carlsson, Richard J. Chappell, Mary E. Fischer, Barbara E.K. Klein, Ronald Klein, Michael Y. Tsai, Karen J. Cruickshanks

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Background:Relationships between brain-derived neurotrophic factor (BDNF), insulin-like growth factor (IGF-1), aldosterone, and cognition in aging were evaluated in the population-based Epidemiology of Hearing Loss Study (1993 to present).Methods:Beginning in 1998 to 2000, cognitive impairment was assessed by report of physician diagnoses and the Mini-Mental State Examination. In 2009 to 2010 and 2013 to 2016, information was collected on diagnosis of mild cognitive impairment/dementia. Decline in cognitive function was assessed by principal component analysis from additional tests administered during 2009 to 2010 and 2013 to 2016. BDNF, IGF-1, and aldosterone were measured in serum collected in 1998 to 2000.Results:There were 1970 participants (mean age=66.9 y; 59.1% female) without cognitive impairment at baseline. Among women, low BDNF was associated with 16-year incident cognitive impairment [hazard ratio=1.76; 95% confidence interval (CI)=1.04, 2.98]. Among men, increasing IGF-1 was associated with decreased risk [per SD: relative risk (RR)=0.57; 95% CI=0.35, 0.92], whereas increasing aldosterone levels were associated with increased risk (per SD: RR=1.28; 95% CI=1.01, 1.62) for 5-year incident mild cognitive impairment/dementia. Overall, low BDNF was associated with increased risk (RR=1.52; 95% CI=1.02, 2.26) for 5-year cognitive decline.Conclusion:Low levels of serum BDNF and IGF-1 were associated with poorer cognition during aging. There may be differential biomarker effects by sex.

Original languageEnglish (US)
Pages (from-to)31-39
Number of pages9
JournalAlzheimer disease and associated disorders
Issue number1
StatePublished - 2020

Bibliographical note

Funding Information:
Supported by Award Number R37AG011099 from the National Institute on Aging (K.J.C.), U10EY06594 from the National Eye Institute (R.K. and B.E.K.K.), and an unrestricted grant from Research to Prevent Blindness.

Publisher Copyright:
© 2019 Wolters Kluwer Health, Inc. All rights reserved.


  • aging
  • biomarkers
  • cognition
  • epidemiology


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