Vascular dementia: current concepts and nomenclature harmonization

Views & Reviews Dement Neuropsychol 2012 September;6(3):122-126 Vascular dementia Current concepts and nomenclature harmonization Lea Tenenholz Grinberg ABSTRACT. Several types of cerebrovascular lesions are associated with cognitive decline, but the role of each type in dementia manifestation has yet to be determined. One of the greatest barriers of conducting clinicopathological studies in vascular dementia concerns the overlapping of nomenclature for these lesions. The aim of the present review was to discuss current nomenclature for cerebrovascular lesions and suggest modifications to allow better diagnostic reproducibility in this field Key words: pathology, Alzheimer’s disease, cerebrovascular diseases, vascular dementia. DEMÊNCIAS VASCULARES: CONCEITOS ATUAIS E HARMONIZAÇÃO DE NOMENCLATURA RESUMO. Diversas lesões cerebrovasculares estão associadas à perda cognitiva. Entretanto ainda não se conhece qual a contribuição exata dessas lesões para quadros os demenciais. Um dos maiores empecilhos para estudos de correlação clinicopatológica em demências vasculares é a heteregeonidade de termos usados para definir essas lesões. A presente revisão discute a nomenclatura neuropatológica atual para lesões cerebrovasculares e sugere alternativas para melhorar a acurácia e reprodutividade do diagnóstico das mesmas. Palavras-chave: patologia, doença de Alzheimer, demência vascular, doenças cerebrovasculares. INTRODUCTION C erebral arteriosclerosis was considered the main cause of senile dementia in the beginning of the twentieth century.1 However, the demonstration of Alzheimer’s disease (AD) type as very frequent in control elderly and demented subjects led to such an extreme shift in this view that for many decades dementia of vascular origin was virtually dismissed in the differential diagnosis of dementia. More recently, vascular dementia again became a focus of attention following clinicopathological studies showing that even a small degree of vascular brain change may cause cognitive decline if occurring in a strategic area.2-3 One of the most important barriers preventing further advances in the understanding of vascular dementia is a lack of a reliable way of determining which element of the cognitive decline is due to vascular changes. Unlike other common causes of dementia, vascular dementia is not easily identifiable by a specific neuropathological hallmark, such as neuritic plaques in AD or Lewy bodies in Parkinson’s disease. In addition, vascular changes are also found frequently in brains of cognitively normal elderly,4 making it difficult to establish a causal relationship between brain lesions and cognitive decline. Moreover, vascular changes are likely to have a synergistic rather than an additive effect to primary neurodegenerative processes.5-8 Therefore, a pathological diagnosis of vascular dementia (VaD) is often reached by excluding other causes. A drastic change in the way cerebrovascular lesions are defined is critical for the creation of a new set of pathological diagnostic criteria.2 Vascular dementia is not a single entity, but an umbrella term to describe cognitive decline due to a series of different vessel disorders, frequently seen in combination with other non-vascular changes. These vessel disorders can induce various types of Department of Neurology, University of California San Francisco - 675 Nelson Rising Lane, San Francisco – CA – 94158 – USA. Departamento de Patologia da FMUSP – Av. Dr. Arnaldo,455 / sala 1353 – 01246903 São Paulo SP, Brazil. Lea T. Grinberg. 675 Nelson Rising Lane – 94158 San Francisco CA – USA. E-mail: Disclosure: The authors report no conflicts of interest. Received June 20, 2012. Accepted in final form August 20, 2012. 122 Vascular dementia: current concepts     Grinberg LT Dement Neuropsychol 2012 September;6(3):122-126 ■ cerebral tissue lesions such as hemorrhage, infarction, hippocampal sclerosis, and white matter lesions.9 Currently, vascular lesions are classified based on their morphological characteristics rather than by their pathogenesis. The aims of this review article were to review characteristics of cerebrovascular lesions associated with cognitive decline, discuss overlapping nomenclature and propose strategies to harmonize the nomenclature adopted for vascular brain disorders. CURRENT CLASSIFICATION AND NOMENCLATURE OF VASCULAR BRAIN DISORDERS Current classifications distinguish vessel disorders from parenchymal lesions. There is a great deal of overlapping among the different categories.10-12,14 VESSEL DISORDERS Vessel disorders are divided into those involving large or small vessels. Large vessel disorders. Atherosclerosis refers to age-re- lated degenerative vessel disorder of medium- to largesized arteries, in which the circle of Willis is the most vulnerable site. Atherosclerosis progression follows a predictive sequence starting with intima proliferation and accumulation of blood-derived lipids and proteins, especially cholesterol within vessel walls, resulting in atherosclerotic plaques and further degeneration and fibrosis of vessel walls.15,16 Atherosclerotic plaques often break up leading to thrombosis or emboli.9,17 Small vessel disorders (Figure 1). Small vessel disease (SVD) encompasses distinct changes such as small vessel arteriosclerosis, arteriolosclerosis, arteriohyalinosis, and lipohyalinosis.9,18,19 Arteriosclerosis resembles large vessel atherosclerosis, with the exception of calcification.12,20 Arteriolosclerosis occurs by concentric hyaline thickening of vessel walls with stenosis of arterioles.20 Lipohya- A linosis is characterized by asymmetric areas of fibrosis, hyalinosis associated with foam cells, and accumulation of blood-derived lipids and proteins.9,21,22 White matter arteries often show loss of smooth muscle cells, fibrosis, and thickening of the basement membrane, as well as enlarged perivascular spaces with leakage of plasma proteins.23 Preferential sites of involvement for SVD are basal ganglia, followed by peripheral white matter and leptomeningeal arteries, thalamus and cerebellar white matter. Cortical vessels are usually spared.24 SVD is an important cause of white matter destruction25,26 and Wallerian degeneration.27 More details about SVD progression can be found elsewhere.24 Sporadic cerebral amyloid angiopathy (CAA) is characterized by amyloid protein, mainly amyloid-b 1-40, deposits in cerebral and leptomeningeal artery, vein and capillary walls. Typically, these deposits are located near the basement membrane or in the smooth muscle cell layer.28,29 CAA rarely leads to lethal hemorrhage,28 and more often to microbleeds,30 capillary occlusion, blood flow disturbances31 and microinfarcts.32 CAA is frequently found together with AD-type changes, but this finding is not universal. VASCULAR-ASSOCIATED PARENCHYMAL LESIONS COMMONLY SEEN IN COGNITIVE DECLINE Parenchymal disorders are mainly divided into ischemic or hemorrhagic. Ischemic. Brain (...truncated)