Midlife Stress in Relation to Late-Life Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease: A 25-Year Follow-Up Study

Abstract

Background/Aims: Psychological stress has previously been associated with higher risk of developing late-life dementia, especially Alzheimer’s disease (AD). This study tested whether longstanding midlife stress is related to cerebrospinal fluid (CSF) biomarkers of late-life AD, such as tau protein and amyloid beta (Aβ). Methods: The study included 79 nondemented females from the Prospective Population Study of Women in Gothenburg, Sweden, who responded to a standardized stress question at baseline (mean age 49 years) and underwent a lumbar puncture at follow-up 25 years later. Multiple linear regression models analyzed the relationships between midlife psychological stress and late-life CSF measures of total tau (t-tau), phosphorylated tau (p-tau), Aβ40, and Aβ42. Results: Longstanding stress in midlife was associated with higher levels of CSF t-tau (β = 0.64, p = 0.01) and Aβ40 (β = 0.60, p = 0.02) in late life. No associations were found between midlife stress and levels of p-tau or Aβ42. Conclusion: The findings suggest that longstanding stress stimulates unspecific neurodegenerative processes, but not the core processes of AD, at least not in the early phase of the disease. The association with higher concentration of CSF t-tau may reflect neural degeneration and the association with higher Aβ40 may be an early sign of Aβ overproduction or cerebrovascular processes in the brain.