Smith, Eric E.Durrani, Romella2022-11-152021-09-24Durrani, R. (2021). Cerebral Small Vessel Disease: Cognitive Reserve and Mediators of Cognitive Decline (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.http://hdl.handle.net/1880/115450https://dx.doi.org/10.11575/PRISM/40417Background: Cerebral small vessel disease (CSVD) is the most common type of cerebrovascular disease that contributes to cognitive decline and dementia. However, persons with the same burden of CSVD often have different cognitive outcomes. Cognitive reserve, defined as the ability to tolerate or adapt to pathology, has been suggested to explain these variations. There are limited studies on cognitive reserve in CSVD, as most studies have focused on Alzheimer’s disease (AD). These studies have also focused on education as the proxy of cognitive reserve, with only a few studies looking at other proxies, such as occupation and leisure activities. Additionally, few studies of cognitive reserve have examined other measures of cerebrovascular disease, beyond white matter hyperintensities (WMH). Objectives: Determine whether cognitive reserve mitigates the deleterious effects of CSVD on cognition, and determine the degree to which cerebral amyloid angiopathy (CAA) biomarkers mediate the effects of CAA on cognition.Methods: Data were analyzed from four multicenter, cross-sectional cohorts. Measures of cerebrovascular disease included: brain infarcts, non-lacunar covert brain infarcts (CBI), WMH, vascular lesion burden, and CAA. Measures of cognitive reserve included: education, occupation, social involvement, physical activity, leisure physical activity, household income, marital status, height, stress, and multilingualism. CAA biomarkers included: WMH, cerebrovascular reactivity (CVR), peak width of skeletonized mean diffusivity (PSMD), mean cortical thickness, and mean cortical thickness in an AD meta-region of interest.Results: WMH, non-lacunar CBI, vascular lesion burden, and CAA were associated with lower cognition. Proxies of cognitive reserve were associated with higher cognition. However, cognitive reserve did not modify the association between CSVD and cognition. CVR, PSMD, and mean cortical thickness in regions typically affected by AD accounted for half of the effects of CAA on cognition; PSMD was the largest contributor.Conclusions: This forms the largest body of work on cognitive reserve within CSVD. Strategies to prevent CSVD-related cognitive decline and dementia include: 1) preventing CSVD, 2) enhancing cognitive reserve, thereby independently increasing cognition---however, this does not mitigate the deleterious effects of CSVD on cognition, and 3) in CAA, maintaining white matter integrity and restoring normal cerebrovascular reactivity.enUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.Cerebral small vessel diseasecognitive dysfunctiondementiacognitive reservewhite matter hyperintensitysilent brain infarctcovert brain infarctsilent strokecovert strokecerebrovascular diseasecerebral amyloid angiopathyBiology--NeuroscienceHealth Sciences--EpidemiologyCognitivedoctoral thesis