Vascular Cognitive Impairment

Cerebrovascular disease (CVD) encompasses a spectrum of vascular pathologies with diverse molecular underpinnings, centered around endothelial cells, that occur with age and insidiously contribute to progressive cognitive impairment and dementia. Quantified vascular pathologies on brain autopsy are considered the second most common pathological correlate of pre-mortem cognitive deficits in dementia syndromes. However, in so far as the cause of Alzheimer’s disease and other neurodegenerative pathologies remains in large part unknown, vascular pathologies are beginning to emerge as putative upstream drivers of brain dysfunction and degeneration, within the category of etiological factors. Indeed, co-pathologies with mixed vascular and Alzheimer’s disease (AD) are prevalent in autopsy series. Thus, progress has been made and the term vascular dementia (VD), as a distinct category of pure dementia subtype, is giving way to a more comprehensive designation, namely vascular contributions to cognitive impairment and dementia (VCID), encompassing the majority of dementia cases. A number of challenges remain for therapeutic developments, from lack of unified clinical and pathological diagnostic criteria to lack of specific biomarkers capturing contributions of molecular drivers of disease. Notwithstanding, given the opportunity for low-cost systemic vascular intervention strategies, three therapeutically relevant questions need to be addressed: (1) Are vascular pathologies that contribute to brain degeneration treatable with existing systemic vascular interventions? (2) Are associated cognitive deficits reversible within certain disease stage(s)? (3) Are there biomarkers that can help diagnose VCID with specificity and sensitivity? This chapter seeks to address these questions in addition to other aspects of VCID by covering the nosology and diagnostic criteria for VCID, advances in knowledge of underlying pathophysiology, diagnostic tools, treatment, epidemiology, and finally disease prevention.