The Science of Vascular Contributions to Cognitive Impairment and Dementia (VCID): A Framework for Advancing Research Priorities in the Cerebrovascular Biology of Cognitive Decline

Abstract

The World Health Organization reports that 47.5 million people are affected by dementia worldwide. With aging populations and 7.7 million new cases each year, the burden of illness due to dementia approaches crisis proportions. Despite significant advances in our understanding of the biology of Alzheimer's disease (AD), the leading dementia diagnosis, the actual causes of dementia in affected individuals are unknown except for rare fully penetrant genetic forms. Evidence from epidemiology and pathology studies indicates that damage to the vascular system is associated with an increased risk of many types of dementia. Both Alzheimer's pathology and cerebrovascular disease increase with age. How AD affects small blood vessel function and how vascular dysfunction contributes to the molecular pathology of Alzheimer's are areas of intense research. The science of vascular contributions to cognitive impairment and dementia (VCID) integrates diverse aspects of biology and incorporates the roles of multiple cell types that support the function of neural tissue. Because of the proven ability to prevent and treat cardiovascular disease and hypertension with population benefits for heart and stroke outcomes, it is proposed that understanding and targeting the biological mechanisms of VCID can have a similarly positive impact on public health.

Keywords: Alzheimer’s disease; Cardiovascular; Cerebrovascular; Vascular cognitive impairment, VCI; Vascular contributions to cognitive impairment and dementia, VCID; Vascular dementia.

Figure 1

The science of vascular contributions to cognitive impairment and dementia (VCID) includes many and diverse vascular diagnoses and conditions, a number of which are represented here. Clinical outcomes range from cognitive impairment (top left) to dementia (bottom left), and cognitive outcomes associated with vascular disease vary not only with the amount and type of injury, but also due to other contributing factors such anatomical location, comorbidities and many other factors. Cognitive impairment may be associated with small vessel insults and limited brain comorbidities, and can be recognized as vascular cognitive impairment (VCI), mild cognitive impairment (MCI), or may go undetected. Dementia may be associated with larger vascular insults (small vessel disease is also typically present), especially in the presence of significant brain comorbidities such as beta-amyloid, tauopathy, TDP-43-opathy, and Lewy bodies/alpha-synuclein.

Figure 2

VCID science overlays relevant diagnoses and conditions including cognitive decline and dementia, AD, cardio- and cerebro-vascular disorders (CVD), stroke. This schematic represents relationships among VCID and the indicated clinical conditions (CVD, stroke, cognitive decline and dementia, AD) in living persons, and does not represent pathologic outcomes.

Figure 3

VCID is interdisciplinary in nature, with the neurovascular unit impacted by the biology of Alzheimer’s disease, stroke, metabolism, and immune function. An integrated multidisciplinary approach is required to gain an understanding of the mechanistic relationships between vascular biology and cognitive outcomes.