Clinical studies of elderly individuals with memory impairment reveal a rapid rate of conversion to Alzheimer's disease (AD) reaching as high as 15% per year. This evidence suggests that significant memory impairment, short of dementia and often denoted as mild cognitive impairment (MCI) in the elderly may be a transition phase between the normal aging process and AD. Individual trajectories of cognitive decline can be quite variable, however, and not all older individuals with cognitive impairment have memory loss as the predominant symptom suggesting considerable clinical and etiological heterogeneity. Further support for etiological heterogeneity comes from recent studies that show significantly increased blood pressure, magnetic resonance imaging and pathological evidence of cerebrovascular disease (CVD) amongst patients with MCI. Given the apparent heterogeneity within the broadly define syndrome denoted as MCI, examination of the various etiologies amongst the varied clinical presentations of MCI could significantly alter our current understanding of the process by which individuals transition from normal aging to dementia. In addition, since CVD is common to an aging population and potentially treatable, understanding the role CVD plays in the expression of MCI and progression to dementia could also result in clinical therapeutic trials aimed at the prevention of cerebrovascular-related cognitive impairment. The prevalence and impact of CVD on the natural history, patterns of cognitive performance or longitudinal cognitive changes in MCI are currently unknown. To address this gap in current understanding, this proposed project will examine the clinical and neurobiological substrate of MCI in a large group of MCI patients selected to have both memory and non-memory cognitive impairments as well as a broad spectrum of CVD severity.
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