Research Project
10271797
SUMMARY/ABSTRACT PROJECT R-1 The effects of inflammation and Alzheimer's disease risk factors on cognition in older adults (Dr. Wong) Alzheimer?s disease (AD) is the most common form of dementia, and the number of people with AD is expected to rapidly grow as the global population ages. Identifying early cognitive and biological changes associated with AD is a priority as potential interventions are likely to be most effective if implemented early in the disease process. Chronic systemic inflammation has been associated with the development of AD and has been linked to accelerated rate of age-related cognitive decline. The role of inflammation in neurodegenerative disorders is complex, and research examining inflammation and other AD risk factors during predementia stages is critical for identifying patients who are most vulnerable to deleterious inflammatory responses. Few studies have examined the interaction of inflammation with genetic and biological risk factors for AD and its effect on cognition or AD progression. Furthermore, advances in methods for detecting inflammatory markers in the blood and neuroinflammation in the brain have the potential to provide new insights regarding inflammation in preclinical AD and mild cognitive impairment (MCI). This study will examine blood-based biomarkers of systemic inflammation using Luminex multiplex assays and molecular imaging of neuroinflammation using a novel third generation positron emission tomography (PET) tracer ([18F] GE-180) in older adults without dementia. Determining the association of these inflammatory biomarkers to cognitive functioning is a primary objective. The influence of genetic risk for AD (apolipoprotein E [ApoE] ?4 allele) and amyloid positivity on the relationship between inflammation and cognition will also be investigated. This project will leverage existing data collected during Phase 1 of the Center of Biomedical Research Excellence (COBRE) project and utilize data that is being collected prospectively from the active cohort that will continue to be followed during Phase 2. The participants are well-characterized, as they have comprehensive neuropsychological testing, neuroimaging, blood assays, and genetic testing completed. These factors greatly increase the feasibility of the project and allow for investigation of cognitive changes over time as well as the interaction of multiple risk factors for AD. Rate of cognitive change as a function of inflammation will be examined in cognitive healthy individuals and individuals with MCI. It is expected that AD risk factors will moderate the relationship between inflammation and cognitive trajectories. This project also aims to determine if systemic inflammation is related to neuroinflammation as measured by GE-180 PET imaging. Findings will enhance our understanding of inflammation in the critical area of preclinical AD, identify neuropsychological outcomes sensitive to inflammatory changes, and facilitate the development of future clinical trials targeting inflammation to prevent disease progression and cognitive decline.
