The role of the cingulate cortex in various trajectories of aging and disease
  
   Lead Investigator:    Elena Dominguez
   Institution      :    University of California Irvine
   E-Mail           :    endoming@uci.edu
   Proposal ID      :    1602



   Proposal Description:
   Aim 1: To determine if cortical thickness in the cingulate cortex can predict longitudinal changes in cognitive performance. Many studies have that shown that structural characteristics of areas such as the hippocampus are predictive of longitudinal decline (Mungas et al., 2005) and subsequent conversion to Alzheimer?s disease (AD) (Csernansky et al., 2005 Eckerstr et al., 2008 Jack et al., 1999). To date, this relationship has yet to be studied in the cingulate cortex, a region that is known to be both involved in successful aging (Fjell et al., 2006a Gefen et al., 2015 F. Lin et al., 2017 Sun et al., 2016) and susceptible to disease-related changes (Braak  Braak, 1991 Huang et al., 2002 Ries et al., 2006). Thus, I aim to examine if cortical thickness of the cingulate cortex can predict longitudinal changes in cognitive performance and clinical progression. I will test the hypothesis that individuals with a thinner cingulate cortex will exhibit: (1) lower baseline cognitive scores, (2) greater longitudinal cognitive decline, and (3) increased risk of conversion to MCI or dementia.    Aim 2: To determine the relationship between cortical thickness, amyloid pathology, and cognitive performance. Previous reports have shown that amyloid deposition is associated with cortical thinning in aging (Becker et al., 2011 Llado-Saz et al., 2015). Contrary to this, some studies have shown that despite having greater cortical thickness, groups of successfully cognitive aging individuals did not differ from cognitively normal elderly controls in amyloid positivity (Dang, Harrington, et al., 2019a) or load (Borelli et al., 2019 Harrison et al., 2018).     Given these two competing theories, I aim to (1) examine the relationship between amyloid load, cortical thickness, and cognition, and (2) examine whether cortical thickness in the cingulate mediates or moderates the relationship between amyloid load, and cognition.