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UBC Theses and Dissertations

Understanding cognitive and physical outcomes in cerebral small vessel disease Dao, Elizabeth (Dai Trang Thi)


Cerebral small vessel disease (cSVD) is a key contributor to vascular cognitive impairment and Alzheimer’s disease (AD), the two most common causes of cognitive impairment and dementia. Given the pervasiveness of cSVD in older adults, it is critical that we better understand the cognitive and physical outcomes of cerebrovascular damage and identify strategies to mitigate its progression. Moreover, it is important to assess the effect AD pathology in cSVD, as the two often co-exist and share common pathogenic mechanisms. Specifically, I investigated the role of Aβ plaques, a pathological hallmark of AD, on cognitive and physical outcomes in older adults with cSVD. Another feature of cSVD is myelin loss and currently its role is poorly understood; as such, I examined the contribution of myelin to cognition in older adults with cSVD. There is mounting evidence to suggest that aerobic training (AT) is a promising strategy to combat cSVD as key vascular risk factors (i.e., hypertension, hypercholesteremia, and type 2 diabetes) are modifiable by exercise; critically, the efficacy of exercise may vary by biological sex. Thus, I conducted an exploratory analysis of a randomized controlled trial to examine: 1) the impact of AT in mitigating white matter hyperintensity (WMH) progression, a predominant cSVD lesion; and 2) whether AT efficacy varied by sex. My research showed that Aβ plaque deposition was negatively associated with both cognitive and physical outcomes. In addition, less myelin was associated with impaired processing speed and working memory. My exploratory analysis did not find that AT significantly reduced WMH progression. However, there was a sex difference in response to AT; AT trained males demonstrated reduced progression compared with AT trained females. Overall, the results of this thesis suggest that therapeutic trials in people with cSVD should consider the effects of both cerebral Aβ plaque deposition and myelin loss on cognitive or physical function and future studies should account for sex differences to better understand the efficacy of exercise training. There has been limited pharmacological progress in treating cSVD; thus, it is critical that we continue to investigate lifestyle strategies to prevent or slow the progression of cSVD.

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