The Contribution of Cerebral Microbleeds to the Clinical and Neuropathological
Pathogenesis of Alzheimer's Disease 
   Lead Investigator:    Michael Alosco
   Institution      :    Boston University School of Medicine
   E-Mail           :    malosco@bu.edu
   Proposal ID      :    1111



   Proposal Description:
   Cerebral small vessel disease (CSVD) is an identified contributor to the pathogenesis of cognitive decline and dementia in Alzheimer???s disease (AD) and related dementias. More recently, there has been increasing focus on the role of microbleeds in the development of cognitive decline and dementia. Microbleeds can occur as a result of damage to the vessel wall subsequent to cardiovascular disease, in addition to accumulation of beta-amyloid. Microbleeds can be detected through magnetic resonance imaging (MRI) and epidemiological studies show a prevalence rate of 15.3. MRI microbleeds have indeed been linked with cognitive decline and increased risk for incident dementia. However, the literature on MRI microbleeds and dementia is not entirely consistent and has largely been without neuropathological confirmation. MRI only estimates the presence of underlying neuropathology and neuropathological studies are needed to better understand the relationship between the presence and number of microbleeds and associated cognitive decline.                                                                   The objective of this study is to examine the relationship between microbleeds and cognitive decline in autopsy participants from the NACC UDS and NDS. The sample will be restricted to those who have available UDS and NDS data. We will examine the association between microbleeds and ante-mortem cognitive and dementia status at their most recent UDS visit prior to death. We will further test whether participants with microbleeds at autopsy had an accelerated cognitive decline, compared to those without microbleeds. All other cerebrovascular pathologies will additionally be included and we will examine the association between microbleeds and the other cerebrovascular pathologies.    Similarly, we will investigate the amount of variance accounted for by microbleeds (and other cerebrovascular pathologies) in the prediction of cognitive decline and dementia compared to neurodegen