Cognitive impairment of vascular origin: neuropathology of cognitive impairment of vascular origin. J Neurol Sci 299(1-2):139-149

Institut de Neuropatologia, Servei Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, 08907 Hospitalet de LLobregat, Spain.
Journal of the neurological sciences (Impact Factor: 2.47). 12/2010; 299(1-2):139-49. DOI: 10.1016/j.jns.2010.08.039
Source: PubMed


The term cognitive impairment of vascular origin is used to designate global cognitive deficits as well as focal neurological deficits such as aphasia, apraxia and agnosia of vascular/circulatory origin. It has been useful for identifying early clinical and neuroradiological alterations that might permit therapeutic strategies geared to curbing the progression of cerebrovascular disease. Multi-infarct encephalopathy, infarcts in strategic areas, lacunae and lacunar status, Binswanger's encephalopathy, hippocampal sclerosis, cortical granular atrophy and watershed infarcts are common lesions. Hypertension and vascular diseases such as arteriosclerosis, small blood vessel disease, inflammatory diseases of the blood vessels, Sneddon syndrome, cerebral amyloid angiopathies, cerebral autosomic dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and Maeda's syndrome are causative of cognitive impairment of vascular origin. Other less common causes are hereditary endotheliopathy with retinopathy, neuropathy and strokes (HERNS), cerebro-retinian vasculopathy (CRV), hereditary vascular retinopathy (HVR) (all three linked to 3p21.1-p21.3), hereditary infantile hemiparesis with arteriolar retinopathy and leukoencephalopathy (HIHRATL) (not linked to 3p21), fibromuscular dysplasia, and moya-moya disease. Lack of uniformity of clinical manifestations, the variety of vascular diseases and circulatory factors, the diverse, but often convergent, neuropathological substrates, and the common association with unrelated neurodegenerative diseases in the elderly, make it hard to assume a single clinical approach in the diagnosis and treatment of cognitive impairment of vascular origin. Rather, environmental and genetic risk factors, underlying vascular diseases, associated systemic, metabolic and neurodegenerative diseases and identification of extent and distribution of lesions with morphological and functional neuroimaging methods should be applied in every individual patient.

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    • "VCI/VaD is the net result of vascular lesions that lead to impairment of brain function (Jellinger, 2007a, 2008a; Ferrer, 2010; Levine and Langa, 2011). Pathologic changes in patients with VCI representing a variety of large and small cerebrovascular and ischemic lesions involving various cerebral lesions are multifold (Table 6). "
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    ABSTRACT: Vascular cognitive impairment describes a continuum of cognitive diorders ranging from mild cognitive impairment to dementia, in which vascular brain injury involving regions important for memory, cognition and behaviour plays an important role. Classification, prevalence, and pathophysiology are a matter of current research. Clinical diagnostic criteria show moderate sensitivity (ca 50%) and variable specificity (range 64-98%). In Western clinical series, VaD is suggested in 8-10% of cognitively impaired elderly subjects. Its prevalence in autopsy series varies from 0.03 to 58%. In contrast to Alzheimer disease (AD) and mixed dementia showing significant age-related increase, the prevalence of VaD significantly decreases after age 80 years. Cognitive decline is commonly associated with widespread small ischemic vascular lesions involving subcortical brain areas. The lesions affect neuronal networks involved in cognition, memory, and behavior. Cerebrovascular lesions (CVLs) often coexist wth Alzheimer-type lesions and other pathologies. The lesion pattern of "pure" VaD differs from that in mixed dementia (AD + CVLs), which suggests different pathogenesis of both phenotypes. Minor CVLs appear not essential for cognitive impairment in full-blown AD, while both mild AD-type pathology and small vessel disease may interact synergistically in promoting and progressing dementia. However, both AD-related and vascular brain pathologies have been reported. Despite recent suggestions for staging and grading CVLs in specific brain areas, no validated neuropathological criteria are currently available for VaD and mixed dementia. Further clinico-pathological studies and harmonization of neuropathological procedures are needed to validate the diagostic criteria for VaD and mixed dementia in order to clarify the impact of CVLs and other coexistent pathologies on cognitive impairment as a basis for further successful therapeutic options.
    Full-text · Article · Apr 2013 · Frontiers in Aging Neuroscience
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    • "Similar issues were recently discussed by Grinberg and Heinsen (2010) in their paper. It is well known that vascular alterations are also frequently seen in cognitively unimpaired subjects making the assessment of the significance of lesions problematic (Ferrer, 2010). Thus, the existence of vascular dementia is still debated and the incidences of dementia caused by pure vascular alterations and incidence of dementia caused by vascular alterations in association with other pathologies vary (Barker et al., 2002; Drach et al., 1997; Jellinger, 2008; Kovacs et al., 2008; Nagata et al., 2007). "
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    ABSTRACT: Here, we summarise the results after carrying out a large survey regarding the assessment of vascular alterations, both vessel changes and vascular lesions in an inter-laboratory setting. In total, 32 neuropathologists from 22 centres, most being members of BrainNet Europe (BNE), participated by filling out a questionnaire with emphasis on assessment of common vascular alterations seen in the brains of aged subjects. A certain level of harmonisation has been reached among BNE members regarding sectioning of the brain, harvesting of brain tissue for histology and staining used when compared to the survey carried out in 2006 by Pantoni and colleagues. The most significant variability was seen regarding the assessment of severity and of clinical significance of vascular alterations. Two strategies have recently been recommended regarding the assessment of vascular alterations in aged and demented subjects. The National Institute on Aging - Alzheimer's Association (NIA-AA) recommends the assessment of hippocampal sclerosis, vascular brain injury and microvascular lesions in 12 regions. Although this strategy will be easy to follow, the recommendations do not inform how the load of observed alterations should be assessed and when the observed lesions are of significance. Deramecourt and his colleagues recommend an assessment and semiquantitative grading of various pathologies in 4 brain regions. This strategy yielded a total score of 0 to 20 as an estimate of pathology load. It is, however, not clear which score is considered to be of clinical significance. Furthermore, in several BNE trials the semiquantitative assessment has yielded poor agreement rates; an observation that might negatively influence the strategy proposed by Deramecourt and his colleagues. In line with NIA-AA, a dichotomised approach of easily recognisable lesions in a standardised set of brain regions harvested for neuropathological assessment and applying reproducible sampling and staining strategies is recommended by BNE. However, a simple strategy regarding assessment of load of alteration is urgently needed to yield reproducible, and at the same time, comparable results between centres.
    Full-text · Article · Jun 2012 · Experimental gerontology
    • "The vessel disorders that are most frequently associated with VaD are atherosclerosis of cerebral arteries (AS), cerebral small vessel disease (SVD), and cerebral amyloid angiopathy (CAA) (Ferrer, 2010; Gorelick et al., 2011; Hachinski et al., 2006; Ince, 2005; Kalaria, 2003; "
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    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.
    No preview · Article · Jun 2012 · Experimental gerontology
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