Recent updates on subcortical ischemic vascular dementia

Abstract

Vascular dementia (VaD) is a history-laden disease entity that dates back to the 19th century when arteriosclerotic brain atrophy due to hardening of the arteries was perceived as the major cause of senile dementia. Its existence had been overshadowed by the emergence of Alzheimer's disease (AD) in the past century and research on AD dominated the field of dementia. Interest in VaD has been revived in recent years as vascular lesions have been shown to make great contributions to the development of dementia, particularly in the elderly. VaD has now evolved into the concept of vascular cognitive impairment (VCI), which encompasses not only VaD but also AD with cerebrovascular disorder and VCI with no dementia. The concept of VCI is intended to maximize the therapeutic potential in dementia management because the vascular component may be amenable to therapeutic intervention particularly in the early stages of cognitive impairment. Subcortical ischemic vascular dementia (SIVD) is pathologically driven by severe stenosis and the occlusion of small vessels that culminate into white matter ischemia and multiple lacunar infarctions in the subcortical structures. The relatively slow progression of symptoms and clinical manifestations associated with cholinergic deficits often make the differentiation of SIVD from AD difficult. The recent development of in vivo amyloid imaging enabled further pathological breakdown of SIVD into pure SIVD and mixed dementia with subcortical ischemia based on the absence or existence of amyloid pathology in the brain. In this article, the authors reviewed the emerging concepts of VaD/VCI and the clinical manifestations, biomarkers, treatments, and preclinical models of SIVD based on the pathophysiologic mechanisms of the disease.

Keywords: Alzheimer's disease; Subcortical ischemic vascular dementia; Vascular cognitive impairment; Vascular dementia.

Figure 1

Representative imaging scans of patients with pure subcortical ischemic vascular dementia (PiB-PET negative) or mixed dementia (PiB-PET positive). The first two axial fluid-attenuated inversion recovery images represent a similar degree of white matter hyperintensities of representative subjects in the PiB-negative (A) and in the PiB-positive (B) group. The T1-coronal images in the third column demonstrate a similar degree of generalized cortical atrophy, including medial temporal atrophy, in both the PiB-negative (A) and PiB-positive (B) groups. The PiB-PET scans in the fourth column demonstrate PiB-negativity and PiB-positivity scans, with the red color representing more intracranial PiB retentions. Abbreviations: PiB, 11C-Pittsburgh compound B; PET, positron emission tomography. Modified from Neurology 77(1): 18-25, 2011.

Figure 2

Pathophysiology of vascular cognitive impairment. Both vascular and neurodegenerative processes culminate into the development of vascular cognitive impairment. The intervention of modifiable vascular etiologies potentially mitigates and slows the cognitive impairments in patients with vascular cognitive impairments. The progression of Alzheimer's pathologies in the brain is not amenable to current therapeutic interventions. Images modified from J Korean Neurol Assoc 21(5): 445-454, 2003.