Article
Brain infarction, dementia, and related vessel disorders: Impact of infarct size, distribution, and its association with vessel and heart disorders
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Published: | August 25, 2015 |
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Objectives: Vascular dementia (VD) can be caused by multiple infarct dementia or strategic infarct dementia. Vascular lesions have been discussed to be associated with Alzheimer's disease (AD). Here, we want to determine the impact of infarct size anddistribution on the degree of dementia, and vessel or heart disorders that are associated with dementia-driving infarcts in VD and AD.
Methods: We studied a sample of 303 human autopsy cases with and without cognitive deficits. The relative volume of the macroscopically visible forebrain infarct lesions was measured. The number of microinfarcts seen in standardized representative brain sections was determined separately as well as their distribution. Based on the distribution pattern we subclassified neocortical, allocortical, subcortical gray matter and white matter microinfarcts. The expansion of atherosclerosis in the circle of Willis (AS), the stage of cerebral small vessel disease (SVD) distribution, and the stage of cerebral amyloid angiopathy (CAA) distribution were determined. The prevalence of myocardial infarction and the clinical dementia rating (CDR) score as a parameter for the degree of dementia were assessed retrospectively, if possible.
Results: In our series of cases allocortical microinfarcts were associated with the CDR-score but not neo- or subcortical microinfarcts, lacunar infarcts or gross infarcts. The frequency of allocortical, mainly hippocampal, microinfarcts was, thereby, associated with the presence of the capillary type of CAA (CAA-type 1), whereas no association was found between microinfarcts and the stage of CAA (considering type 1 and 2), that of SVD, and the expansion of cerebrovascular AS. Moreover, microinfarcts in the neo- and subcortical gray matter did not show an association with CAA-type 1. In contrast, gross and lacunar infarcts were associated with AS. Lacunar infarcts were also associated with the presence of myocardial infarcts at autopsy.
Conclusion: The results of our study indicate an association between capillary CAA (i.e. CAA-type 1) and the frequency of allocortical microinfarcts, which are associated with the degree of dementia as represented by the CDR-score. In the light of blood flow disturbances described in animal models of CAA it is tempting to speculate that capillary CAA in allocortical regions, namely in the hippocampal formation and the entorhinal cortex, causes of microinfarcts occurring in these brain areas and has, in so doing, impact on the development of dementia and in the CAA-type 1-related type of AD.