Vascular dementia: different forms of vessel disorders contribute to the development of dementia in the elderly brain

Abstract

The diagnosis of vascular dementia (VaD) describes a group of various vessel disorders with different types of vascular lesions that finally contribute to the development of dementia. Most common forms of VaD in the elderly brain are subcortical vascular encephalopathy, strategic infarct dementia, and the multi infarct encephalopathy. Hereditary forms of VaD are rare. Most common is the cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Sporadic forms of VaD are caused by degenerative vessel disorders such as atherosclerosis, small vessel disease (SVD) including small vessel arteriosclerosis, arteriolosclerosis, and lipohyalinosis, and cerebral amyloid angiopathy (CAA). Less frequently inflammatory vessel disorders and tumor-associated vessel lesions (e.g. angiocentric T-cell or angiotropic large cell lymphoma) can cause symptoms of dementia. Here, we review and discuss the impact of vessel disorders to distinct vascular brain tissue lesions and to the development of dementia in elderly individuals. The impact of coexisting neurodegenerative pathology in the elderly brain to VaD as well as the correlation between SVD and CAA expansion in the brain parenchyma with that of Alzheimer's disease (AD)-related pathology is highlighted. We conclude that "pure" VaD is rare and most frequently caused by infarctions. However, there is a significant contribution of vascular lesions and vessel pathology to the development of dementia that may go beyond tissue damage due to vascular lesions. Insufficient blood blow and alterations of the perivascular drainage mechanisms of the brain may also lead to a reduced protein clearance from extracellular space and subsequent increase of proteins in the brain parenchyma, such as the amyloid β-protein, and foster, thereby, the development of AD-related neurodegeneration. As such, it seems to be important for clinical practice to consider treatment of potentially coexisting AD pathology in cognitively impaired patients with vascular lesions.

Fig. 1

Infarcts and white matter lesions. A: Large ischemic infarct in the cerebellum (stage of necrosis; arrows). B, C: Lacunar infarcts in the pons (B) and in the basal ganglia (C) (stage of pseudocystic gliosis; arrows). D: Microinfarct in the parietal cortex (stage of gliosis) The arrows indicate the demarcation line of the infarct. E: Large hemorrhagic infarct in the cortex (stage of necrosis). The arrows indicate the infarct demarcation line at the border between the cortical layers I and II, the arrowheads point to the areas of blood extravasation in the hemorrhagic (red) infarct. F: White matter lesion in the frontocentral white matter near the cingulate gyrus (arrow). Note the U-fibers directly underneath the cortical layer VI are intact. Calibration bar in F corresponds to A = 6900 μm, B, F = 5000μm, C, E = 450μm, D = 360 μm. A–E: Hematoxylin & Eosin staining; F: PAS-Luxol fast blue staining.

Fig. 2

Hemorrhage and microbleeds. A, B: Cerebral hemorrhage in the pons (arrows in A). At higher magnification level (B) it becomes evident that blood clots (arrows) displace the vital brain parenchyma. C Microbleed in the basal ganglia. The microbleed, thereby, represents a hemorrhage restricted to blood extravasation into the perivascular space (arrows) without tissue damage and displacement. Note the two arteries associated with the microbleed exhibit pattern of SVD with a concentric intima proliferation and partial fibrosis of the vessel wall. Calibration bar in A corresponds to A = 4500μm, B = 226μm, C = 85 μm. A–B: Hematoxylin & Eosin staining; C: Elastica van Gieson staining.

Fig. 3

Schematic representation of multi infarct dementia, strategic infarct dementia, and subcortical vascular encephalopathy. The gray areas mark the regions where infarcts and white matter lesions are located. In multi infarct dementia multiple microinfarcts, lacunar infarcts, and small large infarcts are distributed all over the gray matter. Strategic infarct dementia is characterized by infarcts in strategic regions that alone explain dementia, i.e., in the hippocampal formation and in the paramedian nuclei of the thalamus. Subcortical vascular encephalopathy is characterized by confluent white matter lesions in the central and peripheral white matter. Small infarcts in subcortical brain regions may also co-occur with this type of VaD. Abbreviations: Amy = amygdala, Bgl. = basal ganglia, CA1 = Ammon’s horn sector CA1, Cing. = cingulate gyrus, ER = entorhinal cortex, F = frontal neocortex, Hypoth = hypothalamus, NBM = basal nucleus of Meynert, T = temporal neocortex, Thal = thalamus.