Stroke, depression and cognitive impairment: biological underpinnings

Submission note: A thesis submitted in partial fulfilment of the requirement for the degree of Doctor of Clinical Neuropsychology to the School of Psychological Science, Faculty of Science, Technology and Engineering, La Trobe University, Bundoora.

The overall aim of this thesis was to examine the biological mechanisms likely to contribute to the high prevalence of post-stroke affective disorders and vascular-related cognitive impairment. This thesis explored the hypothesis that ischemia-associated cellular degeneration is closely associated with stroke associated affective disorders and vascular cognitive impairment. The first of four experimental chapters of this thesis is presented in Chapter 4, and has been published. This chapter presents a meta-analysis of biological markers of post-stroke depression (PSD). This chapter reports on associations of depression with high cortisol levels, low levels of brain-derived neurotrophic factor (BDNF), and smaller volumes of the amygdala. The second experimental study of this thesis has been published and is presented in Chapter 5 (Part A). This chapter investigated whether there was evidence for sustained peripheral inflammation 18 months post-stroke. In addition, the association of inflammatory markers with PSD was also investigated (Chapter 5, Part A). A small clinical study of the same cohort of stroke patients is presented in Chapter 5 Part B, which aimed to identify associations of inflammatory markers with post-stroke cognitive impairment (PSCI) and vascular dementia. This thesis also examined whether ischemia is associated with longitudinal degenerative changes in grey matter (GM) volumes (hippocampus; Chapter 6) and whether these changes were associated with the development of depression and cognitive impairment after ischemic stroke (Chapter 7). Together, the results from the studies conducted in this thesis have advanced our understanding of biological mechanisms likely to contribute to the high prevalence of post stroke affective disorders and vascular-related cognitive impairment. The present thesis showed that ischemia is associated with longitudinal degenerative changes in GM volumes (hippocampus; Chapter 6) and this degeneration may be associated with the development of depressive and cognitive impairment after ischemic stroke. In particular, the findings suggest a central role for the amygdala and frontal cortex in the development of depression after ischemic stroke, and for the temporal lobes and thalamus in the development of cognitive impairment after ischemic stroke.