The effects of cardiovascular risk factors and carbonic anhydrase inhibitors in
  
   Lead Investigator:    Angela Rocchi
   Institution      :    Temple University - Lewis Katz School of Medicine
   E-Mail           :    angela.rocchi@outlook.com
   Proposal ID      :    1481



   Proposal Description:
   We would like to utilize NACC for two project aims:  ? We hypothesize that CA inhibition prevents mitochondrial dysfunction and cell stress/death mechanisms at the early stages of AD pathology, and aim to assess if patients who have been using CAIs systemically for medium-term (months) or long-term (years) therapies, may have reduced risk, delayed onset, and/or slower progression of the disease. We would use the NACC database to assess if it is possible to find a group of patients who have been taking Carbonic Anhydrase Inhibitors systemically for medium or long-term. If so, we will compare them to a control group (no therapy), to assess the percentage of those patients who developed AD or MCI, the age of onset of MCI and AD, and the rates of progression of AD (from MCI, to mild, moderate and severe AD). In addition, we will look at differences in CSF and blood biomarkers of AD pathology and neurodegeneration (A#6153840/42, tau, P-tau, NFL).  ? Here, we propose to test the hypothesis that chronic CV risk factors, such as hypertension, HHC, and hypoperfusion, potentiate the effects of cerebrovascular A#946 on the neurovascular unit, resulting in the dysregulation of similar biomarkers related to cerebrovascular function and neurodegeneration. We aim to use the NACC database to assess blood and CSF biomarker values in different groups: AD/MCI alone, AD/MCI + HHC, AD/MCI + HT AD/MCI+ HT and HHC and non-demented elderly subjects with the same CV risk factors (in the presence or absence of brain amyloid deposition (assessed by PET). Within these groups, we will compare the levels of blood and CSF biomarkers, including blood and CSF levels of A#6153840 and 42, tau, P-tau, NFL, and biomarkers of cerebrovascular dysfunction (CSF/blood albumin, MMPs, endothelial-specific proteins etc).