Endogenous sex hormones, cognitive decline, and future dementia in old men

Ann Neurol. 2006 Sep;60(3):346-55. doi: 10.1002/ana.20918.


Objective: To estimate the association of endogenous levels of bioavailable testosterone and estradiol with risk for cognitive decline and dementia in old men.

Methods: Within the population-based, prospective Honolulu-Asia Aging Study, 2,974 men, aged 71 to 93 years, without dementia were reexamined 3 times over an average of 6 years for development of dementia and cognitive decline. Cognitive decline was measured with the Cognitive Abilities Screening Instrument. Incident dementia was diagnosed according to standard criteria. A total of 134 men experienced development of Alzheimer's disease (AD; including 40 cases with contributing cerebrovascular disease) and 44 experienced development of vascular dementia.

Results: Adjusting for age and other covariates, testosterone was not associated with risk for dementia (using Cox regression analyses) or cognitive decline (using random coefficient analyses). However, higher levels of estradiol were associated with risk for AD (hazard ratio per standard deviation increase, 1.25; 95% confidence interval, 1.05-1.47) and AD with cerebrovascular disease (hazard ratio, 1.19; 95% confidence interval, 1.02-1.38). Also, compared with the lowest tertile of estradiol, men in the middle and highest tertile of estradiol had 0.24 and 0.28 points lower Cognitive Abilities Screening Instrument scores, respectively, for each year increase in age.

Interpretation: In old men, endogenous testosterone levels are not associated with risk for cognitive decline and AD, whereas higher estrogen levels increase risk for cognitive decline and AD.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / physiology
  • Cognition Disorders / etiology*
  • Community Health Planning
  • Confidence Intervals
  • Dementia / complications
  • Dementia / epidemiology
  • Dementia / metabolism
  • Dementia / physiopathology*
  • Female
  • Geriatric Assessment*
  • Gonadal Steroid Hormones / metabolism*
  • Humans
  • Longitudinal Studies
  • Male
  • Neuropsychological Tests / statistics & numerical data
  • Regression Analysis
  • Retrospective Studies
  • Risk Factors
  • Time Factors


  • Gonadal Steroid Hormones