Understanding the pathology of vascular cognitive impairment
Introduction
The role of cerebrovascular disease (CVD) and ischemic brain damage for cognitive decline remains controversial. Dementia related to vascular disorders was first described as βarteriosclerotic dementiaβ [1] and was later replaced by other terms (Table 1).
While not all patients with vascular cognitive impairment (VCI) develop dementia according to standard diagnostic criteria, such patients are at risk of dementia and at least half of them progress to dementia [3]. Morphologic substrates of cognitive impairment resulting from cerebrovascular lesions (CVL) remain confusing, since they constitute a multifactorial disorder related to a wide variety of lesions and causes. Even when cerebrovascular pathology (CVP) appears to be the main underlying process, the effect of damaged brain parenchyma is variable and, therefore, the clinical, radiological and pathological appearances may be heterogeneous. Complicating the diagnosis of VCI are other coexisting pathologic entities in the aging brain.
In contrast to recently refined morphological criteria for Alzheimer disease (AD) and other degenerative dementias [11], [12], no generally accepted and validated neuropathological criteria for VCI have been established up to date, and no definite morphological substrates have been included in the currently used clinical diagnostic criteria for VCI, e.g. DSM-IV, SCADDTC [13] and NINDS-AIREN [14].
Section snippets
Prevalence and incidence patterns
Given the difficulty in diagnosing VCI, considerable methodological and geographical differences, it remains difficult to draw conclusions about its frequency and distribution. Evaluation of 11 pooled European population-based studies of subjects of over age 65 revealed an age-standardized prevalence of 6.4% for all dementias, 4.4% for AD and 2.6% for vascular dementia (VaD) [15]. The incidence varies between 6 and 15/year/1000 persons aged 70 years and older and increases with advancing age
Major morphological substrates
Pathologic changes in the brain related to VCI are multiple; they include arterial territory infarcts, distal field (watershed/borderzone) infarcts, small and medium sized lesions mainly in functionally important brain areas, lacunar infarcts and scars, white matter lesions (WMLs), incomplete ischemic injury, hippocampal lesions and sclerosis. They have been categorized as multifocal and/or diffuse disease and focal, strategically placed lesions. They are caused by many vascular and ischemic
Pathogenesis
The pathogenic factors involved in VCI include the volume of brain destruction, its location, and the numbers of CVLs, but Pantoni [27] emphasized the overlap between vascular and degenerative mechanisms and a lack of correlation between clinical and pathology findings.
Importance of small cerebrovascular lesions
Comparing the neuropathology findings in elderly demented subjects without considerable AD pathology and non-demented controls, Esiri et al. [4] saw correlations of microvascular brain damage with dementia. Severe lacunar state, microinfarcts and cerebral amyloid angiopathy (CAA) had a greater prevalence in the dementia groups, which had less frequent macroscopic infarcts than non-demented. Without differences in severity of extracerebral atheroma, the dementia group more often revealed
Pathophysiology
VaD is thought to be caused by focal or multifocal lesions involving strategic brain areas with deafferentation of frontal and limbic cortical structures with interruption of thalamo-cortical and striato-cortical pathways caused by lesions in basal ganglia, thalamus or connecting white matter. The pattern of cognitive impairment is consistent with models of disturbed cortical and subcortical neuronal pathways [36]. Complex interactions between subcortical lesions and radiologically detected
The enigma of mixed dementia
Mixed type dementia (MD) is characterized by combined pathologies of both AD and VaD, but the distinction between these diseases is controversial. The CERAD classification does not consider MD [45], while in the ADDTC criteria [13], a second CVD in addition to AD must be shown to be causally related to dementia. In the NINDS-AIREN criteria [14], the term AD with CVD is reserved to patients fulfilling the clinical criteria of possible AD who have also clinical and imaging signs of relevant CVD,
Concluding remarks
CVI is a non-frequent heterogenous group of disorders in the course of which multiple ischemic and/or vascular brain lesions of variable etiology result in progressive cognitive impairment. The major subgroups and their causes are summarized in Table 6. The concept that VaD is determined primarily by the volume of infarcted brain has not been confirmed. Cognitive involvement appears to correlate with widespread ischemic and/or vascular lesions throughout the brain with particular involvement of
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