Personality characteristics are important predictors of dementia risk and progression. Additionally, there is a burgeoning interest in the role of personality in the cognitive healthspan and cognitive resilience, both of which are related to the development and progression of Alzheimer’s Disease & Related Dementias (ADRD). In this application, we describe a novel and translational turn in our line of research on personality and ADRD. In Aim 1, we will focus on the direct and indirect role of both personality traits and social support in the cognitive healthspan across 10 studies within 4 countries. We define cognitive healthspan as the slower overall cognitive decline observed 1) prior to clinical diagnosis (dx) of ADRD, 2) a later diagnosis of ADRD, and 3), as a steeper post-ADRD dx decline in cognition. This third definition will be a test of the compression of cognitive morbidity. We will examine the associations between personality traits and these three definitions of cognitive health span, and then further explore the extent to which the associations between personality traits, social support, and cognitive healthspan operate through inflammatory or cardiometabolic pathways. In Aim 2, we will extend our previous work on personality and cognitive resilience (defined as having better than expected cognitive function given post-mortem neuropathology) by testing the direct associations between personality traits, social support, and cognitive resilience and their indirect associations via inflammatory/cardiometabolic markers (as obtain from 5 longitudinal datasets that containing post-mortem tissues samples). In Aim 3, we will address social disadvantage as a moderator of the associations between personality traits, social support, and cognitive healthspan, cognitive resilience, and ADRD. We will test the theory of resource substitution, which predicts that the associations among personality traits, social support, cognitive health span, and ADRD outcomes may be amplified among individuals with lower SES or from under-represented backgrounds. Our use of up to 10 large longitudinal studies for our main research questions will enhance both the replicability and generalizability of our findings. These aims are highly significant and have potential for high impact as they will provide a better understanding of successful aging while tolerating dementia related neuropathology. The results from this work will provide potentially useful targets for prevention, and the knowledge gained will help researchers, health practitioners and policy makers make decisions about preventive medicine approaches to optimizing cognitive healthspan.

Project Narrative Personality traits have been linked to the cognitive healthspan, compression of cognitive morbidity, Alzheimer’s Disease and Related Dementias, and tolerance of Alzheimer’s brain pathology. It is essential to understand more precisely the pathways through which personality traits and ADRD are related; the current application therefore focuses on the role of potential mediators (i.e., inflammatory biomarkers, cardiometabolic biomarkers), as well as socioeconomic risk factors as potential moderators. The use of multiple large longitudinal datasets of aging and dementia will enhance replicability of results, and will be guided by theoretical frameworks of differentiated preservation, preserved differentiation, cognitive reserve, as well as compression of morbidity in late life.