Assessment of executive function declines in presymptomatic and mildly symptomatic familial frontotemporal dementia: NIH-EXAMINER as a potential clinical trial endpoint

Details

• Alternative Title:
  Alzheimers Dement
• Personal Author:
  Staffaroni, Adam M. ; Bajorek, Lynn ; Casaletto, Kaitlin B. ; Cobigo, Yann ; Goh, Sheng-Yang M. ; Wolf, Amy ; Heuer, Hilary W. ; Elahi, Fanny M. ; Ljubenkov, Peter A. ; Dever, Reilly ; Kornak, John ; Appleby, Brian ; Bove, Jessica ; Bordelon, Yvette ; Brannelly, Patrick ; Brushaber, Danielle ; Caso, Christina ; Coppola, Giovanni ; Dheel, Christina ; Dickerson, Bradford C. ; Dickinson, Susan ; Dominguez, Sophia ; Domoto-Reilly, Kimiko ; Faber, Kelly ; Ferrall, Jessica ; Fields, Julie A. ; Fishman, Ann ; Fong, Jamie ; Foroud, Tatiana ; Forsberg, Leah K. ; Gavrilova, Ralitza ; Gearhart, Debra ; Ghazanfari, Behnaz ; Ghoshal, Nupur ; Goldman, Jill ; Graff-Radford, Jonathan ; Graff-Radford, Neill ; Grant, Ian ; Grossman, Murray ; Haley, Dana ; Hsiung, Ging-Yuek ; Huey, Edward D. ; Irwin, David J. ; Jones, David T. ; Jones, Lynne ; Kantarci, Kejal ; Karydas, Anna ; Kaufer, Daniel I. ; Kerwin, Diana R. ; Knopman, David S. ; Kraft, Ruth ; Kremers, Walter K. ; Kukull, Walter A. ; Litvan, Irene ; Lucente, Diane ; Lungu, Codrin ; Mackenzie, Ian R. ; Maldonado, Miranda ; Manoochehri, Masood ; McGinnis, Scott M. ; McKinley, Emily ; Mendez, Mario F. ; Miller, Bruce L. ; Multani, Namita ; Onyike, Chiadi ; Padmanabhan, Jaya ; Pantelyat, Alex ; Pearlman, Rodney ; Petrucelli, Len ; Potter, Madeline ; Rademakers, Rosa ; Ramos, Eliana Marisa ; Rankin, Katherine P. ; Rascovsky, Katya ; Roberson, Erik D. ; Rogalski, Emily ; Sengdy, Pheth ; Shaw, Leslie M. ; Syrjanen, Jeremy ; Tartaglia, M. Carmela ; Tatton, Nadine ; Taylor, Joanne ; Toga, Arthur ; Trojanowski, John Q. ; Weintraub, Sandra ; Wang, Ping ; Wong, Bonnie ; Wszolek, Zbigniew ; Boxer, Adam L. ; Boeve, Brad F. ; Kramer, Joel H. ; Rosen, Howard J.
• Description:
  Introduction:
  
  Identifying clinical measures that track disease in the earliest stages of frontotemporal lobar degeneration (FTLD) is important for clinical trials. Familial FTLD provides a unique paradigm to study early FTLD. Executive dysfunction is a clinically relevant hallmark of FTLD and may be a marker of disease progression.
  
  Methods:
  
  Ninety-three mutation carriers with no symptoms or minimal/questionable symptoms (MAPT, n = 31; GRN,n = 28; C9orf72,n = 34; Clinical Dementia Rating scale plus NACC FTLD Module <1) and 78 noncarriers enrolled through Advancing Research and Treatment in Frontotemporal Lobar Degeneration/Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects studies completed the Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (NIH-EXAMINER) and the UDS neuropsychological battery. Linear mixed-effects models were used to identify group differences in cognition at baseline and longitudinally. We examined associations between cognition, clinical functioning, and magnetic resonance imaging volumes.
  
  Results:
  
  NIH-EXAMINER scores detected baseline and differences in slopes between carriers and noncarriers, even in carriers with a baseline Clinical Dementia Rating scale plus NACC FTLD Module = 0. NIH-EXAMINER declines were associated with worsening clinical symptoms and brain volume loss.
  
  Discussion:
  
  The NIH-EXAMINER is sensitive to cognitive changes in presymptomatic familial FTLD and is a promising surrogate endpoint.
  
  
• Keywords:
  Behavioral Variant Biomarkers C9orf72 Protein Cognition Corticobasal Syndrome Disease Progression Executive Function Female Fluency Frontotemporal Dementia Genetic Humans Inhibition Longitudinal Studies Magnetic Resonance Imaging Male Middle Aged Mutation Neuropsychological Tests Neuropsychology Nonfluent Variant Primary Progressive Aphasia Progranulin Progressive Supranuclear Palsy Semantic Variant Set-shifting Tau Working Memory

  More +
• Source:
  Alzheimers Dement. 16(1):11-21
• Pubmed ID:
  31914230
• Pubmed Central ID:
  PMC6842665
• Document Type:
  Journal Article
• Funding:
  K24 AG045333/AG/NIA NIH HHSUnited States/ ; U24 AG021886/AG/NIA NIH HHSUnited States/ ; P01 AG019724/AG/NIA NIH HHSUnited States/ ; P01 AG066597/AG/NIA NIH HHSUnited States/ ; R01 AG062268/AG/NIA NIH HHSUnited States/ ; U01 AG045390/AG/NIA NIH HHSUnited States/ ; P30 AG013854/AG/NIA NIH HHSUnited States/ ; K23 AG061253/AG/NIA NIH HHSUnited States/ ; U24 AG072122/AG/NIA NIH HHSUnited States/ ; P01 AG017586/AG/NIA NIH HHSUnited States/ ; P30 AG062421/AG/NIA NIH HHSUnited States/ ; P50 AG008702/AG/NIA NIH HHSUnited States/ ; U19 AG063911/AG/NIA NIH HHSUnited States/ ; ALZ/Alzheimer's AssociationUnited States/ ; U01 AG016976/AG/NIA NIH HHSUnited States/ ; AG045390/NH/NIH HHSUnited States/ ; P50 AG005136/AG/NIA NIH HHSUnited States/ ; T32 AG023481/AG/NIA NIH HHSUnited States/ ; R01 AG032306/AG/NIA NIH HHSUnited States/ ; R01 MH120794/MH/NIMH NIH HHSUnited States/ ; P30 AG066509/AG/NIA NIH HHSUnited States/ ; U54 NS092089/NS/NINDS NIH HHSUnited States/
• Volume:
  16
• Issue:
  1
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:4c601b4062d679f2bcdc330bb089b53a0356d87c11b4dc7f18139fa42f1f69b6
• Download URL:
  https://stacks.cdc.gov/view/cdc/84246/cdc_84246_DS1.pdf
• File Type:
  [PDF - 439.30 KB ]