On the Origin of Dementia : a Population Perspective on Risk and Aetiology

Recent years have seen a surge in dementia research, with increasing awareness that preventive strategies are key to curbing the dementia epidemic. Drawing from long-term population-based studies, this thesis describes the burden of dementia in terms of (healthy) life years lost, lifetime risk of developing disease, and the past and potential effects of preventive interventions on dementia incidence. Furthermore, the role of (disturbances in) cerebral blood flow, for instance due to carotid artery stenosis, and that of cerebral autoregulatory mechanisms in the onset of dementia is extensively discussed. In the subsequent chapter, a literature review that ties coronary heart disease and heart failure to the risk of dementia is followed by exploration of potential underlying mechanisms, including thromboembolic disease (e.g. Von Willebrand factor and ADAMTS13), (vascular) amyloid-β, and aortic valve calcification. Finally, the heritability of dementia and Alzheimer’s disease is yielded for both aetiological and predictive purposes. In particular, the role of the Apolipoprotein E (APOE) gene is described in mortality and for clinical trial design, followed by the use of parental family history and common genetic variants for risk prediction. This thesis concludes with methodological considerations and recommendations – or rather a wish list – for future research to strive and take dementia into the realm of forgotten diseases.

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