Doctor of Philosophy (PhD)



Document Type



Alzheimer’s disease (AD) is a heterogeneous brain disease with multiple interacting risk factors, suggesting equifinality. Research indicates that the pathophysiological processes involved in AD are evident years prior to disease onset with significant variability in neurocognitive functioning being apparent during preclinical stages. Identification of individuals in preclinical stages is vital, as earlier interventions may prove more effective at ameliorating AD’s devastating effects. In this respect, clarifying relationships between risk factors and neurocognitive functioning in cognitively intact older adults can improve our understanding of mechanisms involved in preclinical AD, which may allow for earlier detection and intervention. The present study employed Latent Growth Curve modeling to longitudinally examine relevant risk factors relationship with neurocognitive functioning via neuropsychological assessment of executive attention, processing speed, episodic memory, language and working memory in 576 relatively healthy older adults over a three-year period. Results indicated on average Executive Attention/Processing Speed declined over time, while Memory and Language performance benefitted from practice effects over the three-year period. Substantial heterogeneity in initial levels of neurocognitive functioning and in linear changes in these processes were explained by individual differences in patterns of risk and resiliency variables. Specifically, differences in age, sex (men), and race (African Americans) respectively predicted worse neurocognitive functioning and Neurocardiovascular risk, while higher education and estimated intelligence predicted better neurocognitive functioning. Women were significantly higher in Depression/Endocrine risk. Neurocardiovascular and Depression/Endocrine risk factors emerged as unique predictors of worse neurocognitive functioning. Genetic risk for AD (apolipoprotein E genotype: APOE-e4) specifically associated with worse baseline Memory functioning, supporting episodic memory’s role as a neurocognitive endophenotype for AD. APOE-e4 also associated with lower estimated intelligence and Depression but not Neurocardiovascular history. In sum, the present study found distinct yet identifiable cognitive profiles of risk for neurocognitive decline. These results support conceptual models that suggest individual differences in sex, genetic risk, cognitive reserve, medical and mental health comorbidities in combination influence cognitive decline with age. These data have important treatment implications as they strongly indicate that there are modifiable risk factors that influence neurocognitive decline that can be targeted early on through behavioral and/or medical interventions.



Document Availability at the Time of Submission

Release the entire work immediately for access worldwide.

Committee Chair

Cohen, Alex



Included in

Psychology Commons