Cerebrovascular dysfunction : associations with midlife risk factors

Date

2021-05-08

Authors

Gourley, Drew David

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Abstract

While age has the strongest associations with the development of dementia, a myriad of modifiable cardiovascular risk factors exacerbates and accelerate such risk. Identifying the individual and combined effect earlier in life is crucial to reduce their impact and to introduce positive changes in health behaviors. This dissertation focused on associations between traditional cardiovascular risk factors as well as novel measures of vascular pathology to identify negative functional and structural changes in the brain and cerebrovascular circulation. The rationale for these projects is that continued investigation on the impact of individual and aggregate risk from various cardiovascular risk factors will help target early changes in structure and function that contribute to late life cognitive decline. Once clinical deficits are present, it is often too late to intervene. Therefore, the target population was placed on early to late middle-aged adults between 40-64. In the first study, cross-sectional associations between a midlife dementia risk score composed of cardiovascular risk factors and measures of structural integrity in the brain were investigated. We measured the association between two algorithm-based risk scores used to assess dementia and vascular risk with neuroimaging and cognitive measures in middle-aged, cognitively intact adults. The primary findings of the first study were that the dementia risk score was negatively associated with cortical thickness in the superior frontal gyrus and parahippocampal gyrus as well as memory. These findings provide insight into early pathological changes that occur even among low-risk adults. In the second study, we investigated if subclinical elevations in blood glucose concentration were associated with an early marker of cognitive dysfunction, functional connectivity, and whether this relation was modified by physical fitness or physical activity status. We determined the moderating effect of physical fitness on the association between elevated plasma glucose and functional connectivity. We found there was no direct effect of elevated plasma glucose or insulin resistance with functional connectivity between the medial prefrontal cortex and posterior cingulate cortex, and that neither physical fitness nor physical activity status moderated this association. This suggests that there is a threshold at which elevations in metabolic factors influence connectivity. For the last study, we examined the association between midlife extracranial and peripheral atherosclerosis with late-life intracranial atherosclerosis using a novel magnetic resonance angiography technique. Using the community-based Atherosclerosis Risk in Communities study, we examined the association between various measures of extracranial and peripheral atherosclerosis and late-life intracranial atherosclerosis. We found that carotid intima media thickness was associated with greater odds of intracranial plaque presence and a greater burden of intracranial atherosclerotic disease. Taken together, our findings emphasize the importance of improving lifestyle behaviors at midlife as well as before the emergence of clinical pathology, such as diabetes, to reduce risk of late life dysfunction.

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