Salivary cortisol, APOE-ε4 allele and cognitive decline in a prospective study of older persons

Neurobiol Aging. 2011 Sep;32(9):1615-25. doi: 10.1016/j.neurobiolaging.2009.09.007. Epub 2009 Oct 30.


Objective: We determined whether salivary cortisol levels were associated with cognitive decline at follow-up in older persons and whether this association was modified by the APOE-ε4 allele.

Methods: Within the Longitudinal Aging Study Amsterdam (LASA), a population-based prospective cohort study, 911 persons (74.5±7.2 years, 46.4% male) collected salivary cortisol in the morning and late in the evening. At baseline and after 4 years of follow-up, global cognitive functioning, verbal memory performance, and processing speed were assessed. The longitudinal associations between cortisol measures and cognitive decline were estimated using linear mixed models, adjusted for potential confounders and the modifying role of the APOE-ε4 allele was examined.

Results: Lower morning cortisol levels, higher evening cortisol levels, and flattened diurnal variability of cortisol levels were associated with increased risk for memory decline in APOE-ε4 carriers but not in non-carriers.

Conclusion: Our findings suggest that in this older non-demented population APOE-ε4 carriers may be more vulnerable to the potential detrimental effect of hypothalamic-pituitary-adrenal axis dysfunction on verbal memory performance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / pathology
  • Aging / physiology*
  • Apolipoprotein E4 / genetics*
  • Cognition Disorders / genetics*
  • Cognition Disorders / metabolism*
  • Cognition Disorders / physiopathology
  • Cohort Studies
  • Female
  • Gene Frequency / genetics*
  • Genetic Carrier Screening
  • Humans
  • Hydrocortisone / metabolism*
  • Hypothalamus / physiology
  • Hypothalamus / physiopathology
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Pituitary-Adrenal System / physiology
  • Pituitary-Adrenal System / physiopathology
  • Prospective Studies


  • Apolipoprotein E4
  • Hydrocortisone