A dvances in our understanding of vascular cognitive impairment (VCI) have springboarded from further elucidation of the role of vascular risk factors, surgical procedures, medications, and neuroimaging studies that are related to this condition. The main focus of this VCI review will highlight the relation of diabetes mellitus and hippocampal dysfunction in VCI; coronary artery bypass surgery and cognitive decline; the role of cerebral amyloid angiopathy (CAA) in vascular dysfunction; and a discussion of other cardiovascular risk factors, treatment, and neuroimaging findings related to disease progression; and histopathologic and genetic correlates.
Diabetes Mellitus, Hippocampal Function, Cerebral Blood Volume, Glucose, and InfarctsDiabetes increases the risk of both VCI and Alzheimer disease and may do so by the effects of insulin resistance, hyperglycemia-related increases in advanced glycation end products, and via oxidative stress, inflammation, and macrovascular or microvascular injury. 1 Insulin is transported into the central nervous system through the blood-brain barrier by a saturable receptor-mediated process, and insulin receptors are located in astrocytes and neuronal synapses and are highly concentrated in the olfactory bulb, cerebral cortex, hippocampus, hypothalamus, amygdala, and septum. 1 Of these structures, the hippocampus has been a focus of interest in relation to metabolic dysfunction and cognitive impairment in persons with diabetes.Wu et al 2 have shown that in community-based, nondemented elderly who underwent magnetic resonance imaging (MRI) and high-resolution functional mapping of the hippocampus, both diabetes and brain infarcts were associated with hippocampal dysfunction but with separate hippocampal subregions suggestive of distinct underlying mechanisms. Specifically, blood glucose levels were inversely and selectively correlated with dentate gyrus cerebral blood volume, and blood glucose levels were selectively and inversely correlated with total recall on the Selective Reminding Test, whereas CA1 dysfunction was linked to the occurrence of cerebral infarcts, an area known to be differentially vulnerable to transient hypoperfusion. Therefore, these findings clarify how blood glucose levels and brain infarcts in later life may differentially target hippocampal formation and suggest possible mechanisms for prevention of late-life memory decline.Diabetes is nonetheless associated with a variety of types of cerebral damage. In the SMART study of MRI segmentation data in 1043 individuals, of whom 151 had type 2 diabetes, diabetes mellitus was associated with global atrophy, subcortical atrophy, leukoaraiosis, and lacunar infarcts (but not large infarcts) after correction for other common vascular risk factors. 3 In the Adult Changes in Thought Study, a longitudinal, population-based study of aging and cognitive decline, 2 different patterns of cerebral injury at brain necropsy were noted in patients with dementia: Individuals without diabetes had a greater amyloid-B peptide load an...