Approximately 50% of all stroke survivors develop post-stroke cognitive impairment, and acute stroke may especially lead to an accelerated progression of cognitive impairment in the years following stroke. To develop new therapeutic strategies for post-stroke cognitive impairment, it is important to identify the condition’s modifiable risk factors. Along those lines, chronic low-grade inflammation is associated with several risk factors of both ischemic stroke and dementia, including aging and chronic disease (e.g., atherosclerosis, diabetes mellitus, and obesity), as well as Alzheimer’s disease and vascular dementia. Because acute stroke leads to an acute inflammatory reaction, the hypothesis investigated in this doctoral thesis was that inflammation impacts post-stroke cognitive impairment. In this doctoral research project, the aim of my colleagues and I was to elucidate the association between systemic inflammation, both acute and chronic, and the development of post-stroke cognitive impairment.
The doctoral project presented in this thesis was a sub-study of the Norwegian Cognitive Impairment After Stroke (Nor-COAST) study, a cohort study that followed patients with acute strokes from five hospitals in Norway for 3 years following their index hospital stay. Using mixed linear regression models, my colleagues and I found that acute inflammation in blood was associated with cognitive impairment at 3, 18, and 36 months after stroke, as reported in Papers 1 and 2. We demonstrated that association using various inflammatory markers, namely a marker for complement activation, cytokines, neopterin representing Th1-cell activation, neurotoxic kynurenine metabolites, and altered distribution of B6 vitamers. When we investigated chronic inflammation in blood at 3 and 18 months after stroke, the associations were fewer, but we nevertheless found associations between neopterin and cognitive impairment at 18 and 36 months post-stroke (Paper 2), between certain cytokines measured at 18 months and cognitive impairment at 36 months (Paper 1).
As reported in Paper 3, we also examined cognitive trajectories among the participants. We identified three groups with different trajectories: a group with high and increasing cognitive function, a group with moderate and stable cognitive function, and a group with low and declining cognitive function. The risk of belonging to the group with low function compared with the group with high function increased with higher values of inflammatory biomarkers in the blood in the acute phase of stroke. However, a part of that association could be explained by increased pre-stroke frailty. Furthermore, higher concentrations of some cytokines in the acute phase predicted decline or less improvement in cognition over time, and the clinical significance of these associations appeared to be greatest among participants with pre-stroke cognitive impairment.
The three papers in this thesis indicate an association between post-stroke cognitive impairment and systemic inflammation, the negative impact of which seemed to be greatest in the acute phase. Moreover, certain cytokines predicted the further deterioration of cognitive function following stroke, especially for participants with pre-stroke cognitive impairment. With those results, this thesis contributes new, vital knowledge for investigating and designing treatments to prevent cognitive decline after stroke.Fulltext not availabl
