The Protected Survivor Model for associations of cardiovascular risk factors
with cognition depending on outcome age
 
   Lead Investigator:    Jeremy Silverman
   Institution      :    Mount Sinai
   E-Mail           :    CAROLYN.ZHU@MSSM.EDU
   Proposal ID      :    949



   Proposal Description:
   The goal of the proposed research to assess whether those cardiovascular risk  factors associated with risk for cognitive decline (e.g. body mass index [BMI],  systolic and diastolic blood pressure, cholesterol, apolipoprotein E ? e4  allele) vary in this association depending on the age at which the follow-up  assessment (outcome age) is conducted.  Associations of many cardiovascular risk factors identified as predictors of  cognitive impairment in the elderly are diminished or even reversed when  cognition is assessed in very late life. We have previously proposed a  protected survivor model to explain this. This model posits a minority  subpopulation with a protective factor ? genetic or otherwise ? against  mortality and against cognitive decline associated with the level of a risk  factor. As the population ages, the proportion who are protected increases,  especially among those at high risk.  The NACC control sample ? specifically, those with intact cognition at  baseline ? is a potential resource to investigate the utility of this model.  The proposed design will use data on cardiovascular risk factors and  longitudinal measures of cognition for NACC control subjects.  Successful cognitive aging is defined as living to very old age with intact  cognition. This research will characterize specific phenotypes associated with  successful cognitive aging. These in turn can be used in studies seeking to  identify factors ? genetic and non-genetic ? conferring protection against  cognitive decline.  The model suggests that future studies seeking protective factors in very  elderly subjects should compare successful cognitive aging subjects with high  risk factors ? rather than all successful cognitive aging subjects ? with  cognitively impaired subjects.  We hypothesize that in cognitively intact subjects at baseline, associations  between subsequent cognitive trajectories and BMI will diminish or reversed  with increasing outcome age.  We hypothesize that in cogn