On vascular factors, apathy and dementia

Part one of this dissertation describes the results of a randomized controlled trial in 3500 older people evaluating the effect cardiovascular risk factor treatment on incident dementia. The effects on white matter brain anomalies are evaluated in a subset of 200 participants. The main conclusion is that intensive 4-montly monitoring and treatment of cardiovascular risk factors does not convey significant benefits compared to 2-yearly screening with care as usual. Sub analyses of the trial data describe the relation between cerebral blood flow and brain lesions known as white matter hyperintensities and evaluate the feasibility of detecting and the characteristics of individuals with cerebral microinfarcts on 3 Tesla MRI. Part two of this thesis describes the relation between cardiovascular risk factors, apathy and dementia. The literature regarding the prevalence and clinical characteristics of apathy after stroke is reviewed and meta-analysed. Having concluded that apathy is more common in people with a history of vascular disease, data from 21 different studies, involving 47000 individuals worldwide, is analysed, showing that older people with apathy have an increased risk of future myocardial infarction, stroke and mortality, regardless of their history of vascular disease. A subsequent study in 3500 older people shows that apathy symptoms are also associated with an increased risk of future dementia. Finally, using MRI tractography, it is shown that in older people with dementia, a syndrome of behavioural symptoms including apathy may be related to, potentially vascular, damage to the white matter projections of the Nucleus Basalis of Meynert.