Cerebral Small Vessel Disease: Cognitive Reserve and Mediators of Cognitive Decline

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dc.contributor.advisorSmith, Eric E.
dc.contributor.authorDurrani, Romella
dc.contributor.committeememberIsmail, Zahinoor
dc.contributor.committeememberHill, Michael D.
dc.contributor.committeememberMonchi, Oury
dc.contributor.committeememberDukelow, Sean P.
dc.contributor.committeememberPostuma, Ronald B.
dc.dateFall Convocation
dc.date.accessioned2022-11-15T17:42:35Z
dc.date.embargolift2022-09-24
dc.date.issued2021-09-24
dc.description.abstractBackground: 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.
dc.identifier.citationDurrani, 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.
dc.identifier.urihttp://hdl.handle.net/1880/115450
dc.identifier.urihttps://dx.doi.org/10.11575/PRISM/40417
dc.language.isoenen
dc.language.isoEnglish
dc.publisher.facultyGraduate Studiesen
dc.publisher.facultyCumming School of Medicine
dc.publisher.institutionUniversity of Calgaryen
dc.rightsUniversity 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.en
dc.subjectCerebral small vessel disease
dc.subjectcognitive dysfunction
dc.subjectdementia
dc.subjectcognitive reserve
dc.subjectwhite matter hyperintensity
dc.subjectsilent brain infarct
dc.subjectcovert brain infarct
dc.subjectsilent stroke
dc.subjectcovert stroke
dc.subjectcerebrovascular disease
dc.subjectcerebral amyloid angiopathy
dc.subject.classificationBiology--Neuroscience
dc.subject.classificationHealth Sciences--Epidemiology
dc.subject.classificationCognitive
dc.titleCerebral Small Vessel Disease: Cognitive Reserve and Mediators of Cognitive Decline
dc.typedoctoral thesis
thesis.degree.disciplineMedicine – Neuroscience
thesis.degree.grantorUniversity of Calgaryen
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameDoctor of Philosophy (PhD)
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