Banerjee, Gargi; (2019) Clinical relevance of cerebral small vessel diseases in cognitive impairment, neurodegeneration and stroke. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Cerebral small vessel diseases are common age-related processes associated with two important and highly prevalent clinical syndromes: stroke and dementia. Whilst our ability to define a specific small vessel disease neuropathologically (most usually post-mortem) is excellent, it is still difficult to reach a definitive diagnosis during life; there remains an unmet need to accurately classify and quantify different subtypes, especially if effective therapeutic trials are ever to be implemented. Thus, two important outstanding questions regarding cerebral small vessel diseases are: how do these processes contribute to cognitive decline and clinical prognosis, and how can we better recognise small vessel disease subtype and severity during life? The programme of research described in this PhD thesis has three key aims. The first is to explore the role of cerebral small vessel diseases and their neuroimaging markers in specific patient populations. These include patients with cognitive impairment and dementia (a “memory clinic” population), patients with spontaneous (“primary”) intracerebral haemorrhage, and those presenting with cardioembolic ischaemic stroke or TIA (transient ischaemic attack). The second aim is to identify how and whether different small vessel disease subtypes (defined on the basis of intracerebral haemorrhage location) and their burden are associated with particular outcomes in patients with intracerebral haemorrhage. The outcomes of interest are recurrent intracerebral haemorrhage, subsequent cerebral ischaemic events (either ischaemic stroke or TIA), and death. The final aim is to present work from a prospective observational pilot study designed to identify new biomarkers for cerebral amyloid angiopathy, one of the most common cerebral small vessel diseases. In addition to describing the protocol and the recruitment process, results from body fluid analyses (cerebrospinal fluid and blood) and positron emission tomography (using the amyloid ligand 18F-florbetapir) scanning will be presented. The implications and limitations of this work will then be discussed, together with proposals for future work in this field.

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