Cortisol and 10-Year Cognitive Decline in Older People From the General Population

Eur J Neurol. 2025 Mar;32(3):e70056. doi: 10.1111/ene.70056.

Abstract

Objective: The present study examined bidirectional effects between salivary cortisol and cognitive functioning over time. Furthermore, the role of the APOE-ɛ4 allele as a moderator of the associations was investigated.

Methods: Using a prospective population-based study, we analyzed data from 752 older adults followed up over 10 years. A random-intercept Cross-Lagged Panel Model was applied to each combination of one cortisol measure (at waking time, 30 min after waking, 11 am, 8 pm, cortisol awakening response, total daily output, and diurnal slope) and one cognitive measure (primary outcome: Clinical Dementia Rating Scale sum of boxes score, CDR-SB; secondary outcome: Mini-Mental State Examination) resulting in 14 (7 × 2) models.

Results: Between-person effects pointed out that a higher cortisol level at 11 am was associated with increased CDR-SB scores, and a higher cortisol awakening response was associated with decreased CDR-SB scores. Within-person effects indicated that cortisol levels at 11 am and 8 pm, and total daily cortisol output were associated with subsequent lower CDR-SB scores. The APOE-ɛ4 allele did not moderate the relationship between cortisol and cognitive functioning.

Conclusions: Our findings revealed within-person associations between higher cortisol levels and better cognitive functioning at the subsequent follow-up, suggesting cortisol protective effects for cognitive decline.

Keywords: CoLaus|PsyCoLaus; HPA axis; cognition; cognitive decline; cortisol; dementia.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Apolipoprotein E4 / genetics
  • Cognitive Dysfunction* / genetics
  • Cognitive Dysfunction* / metabolism
  • Female
  • Humans
  • Hydrocortisone* / metabolism
  • Male
  • Neuropsychological Tests
  • Prospective Studies
  • Saliva / chemistry
  • Saliva / metabolism

Substances

  • Hydrocortisone
  • Apolipoprotein E4