Understanding immune/inflammatory and vascular mechanisms in brain aging and Alzheimer's disease

National Institute On Aging

Investigators

Linked publications & trials

Abstract

The goal of this project is to use data from existing cohort studies to determine how immune and vascular risk factors affect brain structure and function in older adults. Specifically, we will determine how exposure to chronic systemic inflammation, acute inflammatory insults, and vascular risk factors affects the trajectory of brain structure, brain function, and progression of Alzheimers disease. This will be done using available and to-be-collected data from several large cohort studies, including the Baltimore Longitudinal Study of Aging (BLSA), the Atherosclerosis Risk in Communities (ARIC) Study, and the Womens Health Initiative Memory Study (WHIMS). Using data from the BLSA, a longitudinal cohort study started in 1958, we can examine how past exposures relate to longitudinal changes in brain structure and cognition spanning multiple decades. For example, we are currently examining how acute illness or injury (as indicated by hospitalization) is associated with longitudinal changes in brain structure. Preliminary results from this analysis suggest that an association exists between exposure to acute illness and injury and longitudinal declines in brain volume. We are also examining the relationship between chronic infection with human herpesvirus and longitudinal changes in brain structure and function using longitudinal neuroimaging and cognitive data from BLSA. Although research is still underway, we have already identified an association between past symptomatic human herpesvirus infection and longitudinal changes in brain volume, which persist after accounting for medical comorbidity. We are examining similar research questions using data from the ARIC study, an ongoing community-based study of Black and White participants which began in 1987. Using data from this cohort, we have demonstrated an association between midlife vascular risk factors, midlife systemic inflammation, and adverse neurocognitive outcomes. Recently, we demonstrated that greater white matter hyperintensity volume, especially in Black participants, is associated with elevated cortical amyloid, a protein central to Alzheimers disease (Walker et al., JAHA, 2021). In the coming years, we will continue to characterize immune and vascular risk factors in these cohorts to determine whether these exposures are risk factors for Alzheimers disease, dementia, and dementia endophenotypes defined on neuroimaging.