The Effects of Cognitive Reserve on the Cognitive Performance of Patients with Vascular Cognitive Impairment

Background The term vascular cognitive impairment (VCI) refers to patients with cognitive impairment or functional disability secondary to stroke or relevant cerebrovascular pathologies. However, the presence of cerebrovascular pathologies does not necessarily lead to evident cognitive impairment is common. It is not known why some patients are more capable of enduring the observed pathologies. The cognitive reserve (CR) theory has been proposed to account for similar dissociation in patients with Alzheimer’s disease (AD), but it is not known whether CR is applicable to patients with VCI. Aims The project intends to test whether the trajectories of cognitive performance in patients with VCI can be accounted for by the key assumptions of CR; and to test whether CR can modify the associations between vascular pathologies and cognitive performance. Methods and Data Analyses The project consists of four studies. Study 1 involves recruiting 320 participants with VCI from the Stroke Registry of Lin-Kou Chang Gung Hospital and new patients having stroke or transient ischemic attacks in recent 3 months. All need to complete two phases (baseline; ＞= 18-month follow up) of comprehensive neuropsychological assessment and brain imaging. Education, mid-aged occupation, and engagement in leisure activities will be quantified as proxy measures of CR. The effects of these proxies on the associations of vascular pathologies (e.g., atrophy, infarcts, white matter hyperintensities) with cognitive performance will be examined by hierarchical multiple regression. Study 2 involves testing the possibility of empirically-derived measures of CR to explain the associations of vascular pathologies with cognitive performance. The empirically-derived CR is based on latent variable modelling to decompose a cognitive function into several components: brain-related, demographic-related, and a residual term (i.e., CR). This will be followed by a series of analyses including ordinal logistic regression, Cox proportional hazards model, linear regression for validating the feasibility of this approach for defining CR. The associations of the empirical-derived CR with the other potential indicator of CR, and how CR modifies the trajectories of the other specific cognitive function will be examined. Studies 3 and 4 attempt to test one important assumption that separates CR from other reserve theories – compensation, by application of multi-modal fMRI for cerebral perfusion, cerebrovascular reactivity (CVR), and resting-state functional connectivity. Participants with vascular mild cognitive impairment (vaMCI) will be grouped into several subtypes based on cognitive impairment profile. The differences in the activation patterns of perfusion, CVR, and functional networks in different brain regions will be compared. The changes in the cerebrovascular status between 2 phases will be regressed to the changes in cognitive performance by controlling for CR. Expected Outcomes We predict that both proxy and empirically-derived measures of CR will not only modify the relationships between cerebrovascular pathologies and cognition in patients with VCI, but also the trajectories of cognitive performance and cerebrovascular pathologies between two phases. The differences in activation patterns based on perfusion, CVR, and functional connectivity can be detected across different brain regions or networks to reflect the effects of compensation, which will be more evident in participants with higher CR.

Project ID:PF10901-0370
External Project ID:MOST107-2410-H182-008-MY3