Relative contribution of Alzheimer and vascular pathology to brain and
hippocampal atrophy 
 
   Lead Investigator:    Howard Crystal
   Institution      :    SUNY Downstate (Brooklyn, NY)
   E-Mail           :    howard.crystal@downstate.edu
   Proposal ID      :    56



   Proposal Description:
   The hypothesis to be tested in this proposal comes from an alternative model (figure 2).  In addition to the causes of cell loss in figure 1, it also proposes that vascular risk factors may be associated with atrophy by a ???non-infarct and also non-AD??? route (arrow 5). This proposal aims to evaluate the contribution of processes represented by arrows 1, 2, and 5 to brain and hippocampal atrophy.  The relatively unique part of this research is focus on arrow 5 ??? vascular risk factors that lead to cognitive impairment by mechanisms other than AD or strokes.  We offer a somewhat different interpretation to two widely acknowledged observations from clinicopathological studies.  The first observation is that relatively pure vascular dementia (defined by tissue loss associated with infarcts in patients lacking AD, dementia with Lewy bodies, or other likely degenerative cause of dementia) is very uncommon accounting for 10 or less of all cases of dementia (Heyman, Fillenbaum et al. 1998 Langa, Foster et al. 2004).  The second observation independently found in the Einstein Aging Study (in analyses led by the principal investigator) (Crystal, Dickson et al. 2000), the Honolulu Aging study (White, Petrovitch et al. 2002), and the Religious Order Study (Snowdon 1997 Snowdon, Greiner et al. 1997)have suggested that in very elderly patients, or patients with hypertension, diabetes, or heart disease, a much smaller burden of AD pathology is needed to bring about dementia than in younger patients without significant co-morbidity. It is said that co-morbidity ???lowers the threshold??? of AD pathology needed, but if so, how does it do that?  We propose that ???pure??? vascular dementia is uncommon because as figure 1 illustrates risk factors that are associated with infarcts are also associated with AD.  The hypothesis to be tested in this proposal offers an explanation for the second observation ??? less AD pathology is needed to ???cause??? dementia in elderly patients or i