Amyloid ß42 and Total Tau Levels in Cerebrospinal Fluid Associate with Survival in an 85-Year-Old Population-Based Cohort Followed until Death.

BACKGROUND: Dementia of Alzheimer's type (AD) is related to decreased survival. It is not clear whether also biological markers of AD are related to mortality. Low levels of amyloid beta-42 (Aß42) and high levels of total tau (T-tau) protein in cerebrospinal fluid (CSF) are established biomarkers for AD. OBJECTIVE: Our aim was to investigate whether levels of Aß42 and T-tau are associated with survival among octogenarians independently of dementia status. METHODS: Sixty-five 85-year-olds underwent lumbar puncture and were followed with repeated neuropsychiatric examinations until death. RESULTS: Lower CSF Aß42 (p = 0.010) and higher CSF T-tau (p = 0.005) at the age of 85 were associated with lower survival independently of dementia status at baseline and follow-up. Low CSF Aß42 and high CSF T-tau were also related to baseline dementia at the age of 85 years, and lower CSF Aß42 with increased dementia incidence during the first 3 years of follow-up. CONCLUSIONS: Biological markers of AD are associated with mortality in octogenarians. The reason for this needs further study. Our findings highlight the importance to consider the competing risk of death when evaluating biological markers of AD in the very old.

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

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 (Aß). 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), Aß40, and Aß42. RESULTS: Longstanding stress in midlife was associated with higher levels of CSF t-tau (ß = 0.64, p = 0.01) and Aß40 (ß = 0.60, p = 0.02) in late life. No associations were found between midlife stress and levels of p-tau or Aß42. 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 Aß40 may be an early sign of Aß overproduction or cerebrovascular processes in the brain.