Diabetes and microvascular disease in Vascular Cognitive Impairment

Abstract

The contribution of cerebrovascular disease in the development of cognitive dysfunction and dementia is increasingly recognized. Cerebrovascular damage is heterogeneous, ranging from a clinical stroke to more insidious brain changes. The term vascular cognitive impairment (VCI) has been introduced, which refers to the entire spectrum of cognitive disorders associated with and presumed to be caused by any form of cerebrovascular disease. VCI also refers to different pathophysiological processes. Brain imaging, in particular magnetic resonance imaging (MRI), plays an important role in the assessment of these underlying processes. This thesis focuses on brain imaging markers of VCI. Firstly, brain imaging markers of type 2 diabetes mellitus (T2DM) were investigated. T2DM is a risk factor for cognitive decline and therefore considered as a risk factor for VCI. The underlying mechanisms of T2DM-associated cognitive dysfunction are, however, largely unknown. The main conclusion is thatT2DM is associated with various forms of brain damage, reflecting neurodegenerative and vascular disease, both global and regional. Most consistently, people with T2DM show slightly more global brain atrophy than is seen in normal aging. The medial temporal lobe is probably a preferential location. Moreover, vascular lesions are seen more often, particularly lacunar infarcts. The association between T2DM and white matter hyperintensities and microbleeds is less clear. The mentioned brain abnormalities are seen at the population-level, and are heterogeneous, non-specific and subtle as compared to normal ageing. Currently, diagnostic and prognostic values of individual MRI markers are insufficient with regard to T2DM-related cognitive decline. The challenge for further research will be to incorporate different imaging markers that add to the increased risk of dementia in a prediction model. Furthermore, cerebral microvascular lesions (microinfarcts and microbleeds) were investigated as etiological and prognostic markers of VCI. With new imaging techniques at 7 Tesla MRI we are now, for the first time, able to visualize microinfarcts in vivo. Moreover, the detection of microbleeds is highly increased at 7 Tesla MRI compared with regular field strength. We investigated healthy persons, patients with early stages of Alzheimer’s dementia, and patients with a transient ischemic attack or stroke. Both microinfarcts and microbleeds at 7 Tesla MRI are common and also present in healthy persons. On the other hand, microvascular lesions are more common in patients with stroke or dementia, but are not clearly related to cognitive performance in these patient groups. It appears that at the population-level, microvascular lesions could be a marker of future risk for stroke and cognitive decline. In patients with stroke or dementia, the overall burden of other vascular and neurodegenerative pathologies will be higher, which may mask the relatively subtle relation between microbleeds and cognition.