An undesired outcome of an aging society is the increasing prevalence of age-associated diseases. Among these emerging challenges, inadequate treatment for dementia is one of the biggest unmet healthcare needs globally. Alzheimer’s disease (AD) and vascular dementia (VaD) are considered the two major age-related causes of dementia. We chose vascular cognitive impairment (VCI) in this proposal as VCI more accurately covers the full spectrum of symptoms and recognizes that the mechanisms involved are complex and heterogenous: not only systemic or local large or small cerebral vessel disease resulting in overt strokes or microinfarcts, microhemorrhages, and white matter injury, but also neurodegeneration and AD pathology.
Changes in the brain vasculature are common in aging and associated with vascular risks such as hypertension, diabetes, cardiovascular disease, obesity, and hyperlipidemia. Both VCI and AD share many of these risk factors, and the interplay between these diseases is complex and not well understood. Both pathologies can occur in the same individual, i.e. mixed dementia where both AD pathology and vascular changes consistent with VCI are present. Vascular risk factors are notably high and increasing in Singaporeans resulting in cerebrovascular disease (CeVD), a major contributor to VCI. Consequently, reducing the risks of and morbidity due to VCI with or without concomitant AD, are critical to reduce human and economic cost of dementia. The difficulty in differentiating AD,VCI, and other pathologies without postmortem examination are alleviated by recent advances in positron emission tomography (PET) to image the two pathological hallmarks of AD, i.e. β–amyloid peptide (Aβ) and microtubule associated tau protein in neurofibrillary tangles, as well as magnetic resonance imaging (MRI) for CeVD making pre-mortem diagnosis increasingly possible and provides opportunities to gain insights into the pathophysiology of VCI. Moreover, blood biomarkers for AD pathology and CeVD have also rapidly developed.
