Modeling Cognitive Trajectories in multiple proteinopathies

 
   Lead Investigator:    Shama Karanth
   Institution      :    UK Sanders-Brown Center on Aging
   E-Mail           :    shama.karanth@uky.edu
   Proposal ID      :    1352



   Proposal Description:
   Multiple proteinopathies (Tau, Amyloid beta, Alpha-Synuclein, TDP-43) - misfolded proteins that accumulate and destroy neurons -- co-exist in varying degrees in the same brain. It is now known that accumulation of proteinopathies leads to cognitive decline. However, the clinical presentation, associated predictors, and cognitive trajectories are not well understood.     Method: We will include 375 participants enrolled in the University of Kentucky Alzheimer's disease center, came to autopsy, had available data on Alzheimer disease (AD) pathology (Tau, A#946), #945 - synuclein (#945 -Syn), transactive response DNA-binding protein 43 (TDP-43), and satisfied criteria of having at least misfolded tau (Braak stage I-VI). Participants at UK-ADC have longitudinal follow up with neuropsychological tests conducted annually. These tests will be used to identify latent groups. We will then validate our model using the data from National Alzheimer's coordinating center (NACC). The research will help identify the cognitive trajectories among proteinopathy groups.                    Aims and objectives:  1) To identify latent group trajectories over time using group based multi trajectory models (GBMTM) to identify trajectories of cognitive decline among proteinopathy groups.     2) To estimate the change in cognitive function in various cognitive domains over time in multiple proteinopathies.     3) To estimate the predictors of the identified latent groups using polytomous logistic regression.    4) To validate and compare the latent group trajectory models (GBMTM) using NACC data.     5) To compare the frequency and associated predictors of the multiple proteinopathies using the UK-ADC and NACC data.