LIFECOURSE PSYCHOSOCIAL STRESSORS, IMMUNE FUNCTION, INFECTION, AND COGNITIVE DECLINE & DEMENTIA

The over five million people in the U.S. living with dementia are at an elevated risk of
other negative health outcomes due to a diminished ability to care for themselves, contributing
significantly to healthcare costs. There is evidence that traumatic life events (TLE) influence laterlife cognitive function and decline through chronic activation of the HPA axis. One likely
mechanism through which TLEs impact cognition is immune system alterations.
Using data on 7,785 participants aged 65+ from the Health and Retirement Study (HRS)
and 1,337 participants aged 60+ from the Sacramento Area Latino Study of Aging (SALSA), we
investigated these relationships. In HRS, we estimated the association between TLEs and cognitive
trajectories and incident dementia from 2006 to 2016. In SALSA, we estimated the associations
between baseline immune biomarkers and cognitive outcomes over 10 years. Linear mixed effects
models were used to examine these associations and potential interactions or effect measure
modification. Stratified cumulative incidence functions were calculated to investigate risk of
dementia.
We found that TLEs were associated with a higher level of cognitive function and faster
rate of decline but not with dementia incidence. The associations were strongest among those who
experienced TLEs in late life and those with the lowest educational attainment. However, the type
of TLE determined not only the strength but also the direction of the association. We also found
that IL-6, TNF-alpha, and CMV IgG levels were associated with poorer cognitive function in
SALSA, and the identified relationships were modified by educational attainment. Additionally,
IL-6, TNF-alpha, and HSV-1 interacted with cortisol to alter the relationships with cognitive level
and age. We did not find any statistically significant associations between exposures and dementia
incidence.
These findings suggest that TLEs may impact cognitive function and rate of cognitive
decline in late life, timing of these events within the lifecourse is important, and these relationships
are modified by educational attainment. Furthermore, elevated immune biomarkers may be
indicative of lower cognitive function or accelerating decline in older populations. These
relationships were modified by educational attainment, and cortisol may interact with immune
cells to alter the associations with cognitive outcomes.