2024 Theses Doctoral
Effects of Carotid Intima-Media Thickness and Infections on Cognition
Carotid intima-media thickness (IMT) is a measure of atherosclerosis. A large carotid IMT may be indicative of an impaired blood-brain barrier, providing a pathway for infections and inflammation to more readily enter the brain to contribute to neuronal damage as proposed by the ‘microbial hypothesis’. However, no consensus exists regarding the effects of carotid IMT and infections on cognitive decline. Therefore, the goal of my dissertation was to investigate the potential mechanisms proposed by the ‘microbial hypothesis’ that may result in the outcome of cognitive decline. This goal was accomplished through investigating three specific aims.
First, I conducted a scoping review to examine and synthesize existing literature assessing the effects of either carotid IMT or infections on the outcome of change in cognition over at least two years. Secondly, I empirically assessed the association between mid-life carotid IMT and late-life cognitive function at baseline and over time in a well characterized cohort. Finally, in the same cohort, I examined the association between mid- to late-life hospitalized infections and late-life cognitive function at baseline and change over time.
Studies included in the scoping review moderately supported an association between carotid IMT and decline in global cognition, though evidence for an association between infections and cognitive decline is lacking. Infections most commonly were identified using antibodies, which are representative of past infections and may explain null findings. When examining carotid IMT empirically, I found no association between mid-life carotid IMT on 6-year change in late-life global cognitive function, however there was a significant association between greater carotid IMT and decreasing executive function scores over time.
In a secondary analysis, I was able to expand follow-up time for global cognition up to 21 years, beginning in mid-life immediately following last carotid IMT measurement and found a significant association with change over time with this approach. This may support the need for interventions for reducing or preventing atherosclerosis earlier in the life course to prevent cognitive decline and potentially halt progression to dementia.
In the same cohort, I found no significant associations between mid- to late-life hospitalized infections and 6-year change in late-life cognition for global cognition or domains. However, a history of having a hospitalized infection was significantly associated with baseline global cognition and baseline scores for language and executive function, but not memory. This may support theories that infections may result in faster rates of decline immediately following infections while then returning to normal rates in later life, however further examination of trajectories immediately after infections is needed. Results from this dissertation do not directly support the ‘microbial hypothesis’, however, they do provide insight that may be applicable to future studies examining these relationships.
Subjects
Files
- Vollmer_columbia_0054D_18838.pdf application/pdf 3.52 MB Download File
More About This Work
- Academic Units
- Epidemiology
- Thesis Advisors
- Factor-Litvak, Pam
- Degree
- Ph.D., Columbia University
- Published Here
- October 16, 2024