Potential Therapeutics for Vascular Cognitive Impairment and Dementia.

Cognition is the mental process of acquiring, understanding, and storing knowledge through senses, experience, and thought. The proper operation of the cognitive process requires the structural and functional interaction of neurons with their surrounding vasculature, i.e., a constant and appropriate supply of oxygen, glucose, and other nutrients for the activity demands, as well as removal of a variety of bio-metabolites. The close correlation between the functional integrity of neurons and their vascular support is mainly due to the fact that the brain does not have much energy reserve but constantly consumes a lot of energy (2% of total body mass needing 15% cardiac output, and consuming 25% of body oxygen and 25% total body glucose [1]). A reduced blood flow, no matter acutely or chronically, would certainly jeopardize the cognitive process. A subset of stroke survivors, for instance, exhibits vascular cognitive impairment (VCI; 62.6% at 3 months post-stroke [2]) and a third of stroke patients would develop to dementia between 1 and 3 years post-stroke [3, 4], especially in those whose blood circulation in the hippocampal and the prefrontal areas is dramatically affected. Dementia is derived from the Latin word, demens, or dement, meaning ‘out of one’s mind’. Dementia, one of the most disabling health problems, affects the quality of life of affected and their caregivers. Because of brain’s high energy consumption, it is not surprising that vascular pathology has a central role in cognitive deterioration [5] in almost all types of memory disorders and has a worldwide incidence of approximately 1 in 20 people over the age of 65 [6]. Vascular dementia (VaD) is currently the second leading form of dementia (20% [7]), following Alzheimer’s disease (AD: 50%–75%), and followed by dementia with Lewy bodies (5%), and frontotemporal dementia (5%). Patients with VaD often show memory loss and dysfunctions of attention and task execution, such as slowed thinking, disorientation, diminished abilities of planning, reasoning, and judgement, and reduced capacities for problem solving [8, 9]. Activities of daily living (ADL) are also impaired in VaD patients. This review focuses on potential neuropharmacology of VCI and VaD, especially of those recent preclinical and clinical studies related to rescuing cognitive functions from ischemic injuries, while the underlying pathological mechanisms [10] are not discussed in detail. Not covered in detail are also the clinical coexistence of VaD and AD [11, 12] and the complicated nature that vascular pathology may unmask preexisting pathology underlying AD and other memory disorders, or significantly deteriorate cognitive impairments [13-16]. About 40% of AD patients also have some forms of vascular cognitive impairment and dementia (VCID) [17-19]. On the other hand, amyloid pathology contributes to small vessel disease and reduces blood flow through vasoconstriction [20, 21]. VCD and VaD are basically discussed as one type of memory disorders, although they actually encompass diverse subtypes and differ in clinical presentation. These are all important issues in the pathology of memory disorders. The readers are, however, referred to other excellent reviews [5, 7, 22-26].