Cerebrovasculature and Cognition in Middle Aged Adults At Risk for Alzheimer's Disease

Abstract

Alzheimer’s disease (AD) is the most common form of dementia. There is currently no treatment that will delay, halt, or prevent the onset of AD. If a disease modifying therapy were to be implemented, it has been proposed that the earliest stages of the disease must be identified to target individuals in whom treatment would be most effective. The aim of this study was to examine subtle changes in cognition and physiology in middle aged (40-60 years old) subjects at increased risk for AD due to family history. To accomplish this, the project used cognitive tasks that were developed to target specific subregions of the medial temporal lobe, the first area of the brain impacted by AD pathology. Additionally, neuroimaging was used to characterize cerebrovascular function using two metrics: cerebral blood flow (CBF) and cerebrovascular reactivity (CVR). Finally, the relationship between cognitive testing and cerebrovascular function was analyzed. Results showed that the at risk group performed worse on a number of cognitive tests targeting subregions first affected by AD pathology. In contrast, there were no differences between groups in cerebrovascular function or brain volumes. However, CVR correlated with several cognitive tests in the at risk group. These results indicate that there are subtle cognitive differences between middle aged subjects at risk for AD and control subjects, and these differences are likely driven by AD pathology. While there were no group differences in neurovascular function, it is possible that cerebrovascular reactivity may influence individual cognitive performance in these at risk subjects.