PSYCHOLOGICAL STRESS IN MIDLIFE ASSOCIATED WITH HIGHER LEVELS OF CSF T-TAU AND AB40 IN LATE-LIFE: A 25-YEAR LONGITUDINAL POPULATION STUDY OF WOMEN

Abstract

It has been suggested that psychological stress may increase the risk of dementia. We have previously found that longstanding stress in middle-aged women increased the risk of late-life dementia, Alzheimer’s disease (AD) and temporal lobe atrophy. This study aimed to analyzes the relationship between midlife stress and late-life levels of amyloids and tau proteins, measured in cerebrospinal fluid (CSF). He analyses originate from the Prospective Population Study of Women in Gothenburg, Sweden, a study initiated in 1968 (n=1462), and with several subsequent follow-up examinations. Psychological stress was reported according to a standardized question at baseline. Lumbar puncture (LP) was conducted in 1993-94, and levels of beta-amyloid (Aβ40 and Aβ42), total tau protein (t-tau) and phosphorylated tau protein (p-tau) were measured in CSF. This secondary study includes 81 women, i.e. all study participants who responded to the stress-question at baseline 1968 (mean age 49 years) and also took part in the LP study in 1993-94 (mean age 74 years). The participants were born 1908 (n=3), 1914 (n=7), 1918 (n=33), and 1922 (n=38). Twenty women (25%) reported frequent stress at baseline. Age-adjusted logistic regressions showed that midlife psychological stress where associated with higher levels of t-tau (OR 2.31, 95% CI 1.25-4.28, p=0.008) and Aβ40 (OR 1.79, 95% CI 1.06-3.02, p=0.03) in late-life. No associations were found between stress and levels of Aβ42 (p=0.17) or p-tau (p=0.33). The results indicate that longstanding stress might affect neurodegenerative processes in brain. The higher concentration of t-tau can reflect a neural disintegration, and higher Aβ40 can be an early sign of amyloid-beta overproduction. Levels of AB42 and p-tau were however not affected, opposite with is normally seen in persons diagnosed with AD.