Areas of abnormal signal intensity and hemispheric white matter on magnetic resonance imaging (MRI) studies have been termed leukoaraiosis (LA). This radiographic abnormality increase in prevalence with advancing age and is present to a variable degree in a substantial proportion of elderly individuals. LA has been consistently associated with the presence of certain vascular risk factors, particularly hypertension. The overall goals of this project are twofold. First, to provide support for the concept that LA contributes to cognitive impairment in elderly individuals in a manner that is independent and additive to that of the primary neurodegenerative process in AD. Second, to support the concept that MRI can provide quantitative measures of two independent pathologic processes that lead to cognitive impairment in elderly individuals--MRI measures of the LA burden quantify cerebral damage due to the hypertension/vascular disease, and MRI-based hippocampal volume measurement quantify the severity of medial temporal lobe damage due to the neurodegenerative pathology of AD. We propose four specific aims:
Specific Aim #1 : To test the hypothesis that LA is associated with cognitive impairment.
Specific Aim #2 : To test the hypothesis that LA is associated with clinical/laboratory variables that imply a vascular/hypertensive etiology (vascular risk factors) and not with variables that are highly associated with AD (clinical group membership, APOE epsilon 4).
Specific Aim #3 : To test the hypothesis that hippocampal atrophy is not associated with clinical/laboratory variables that imply a vascular/hypertensive etiology (vascular risk factors), but rather with variables that are highly associated with AD itself (clinical group membership, APOE epsilon 4).
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