Details:

Alternative Title:
Alzheimers Dement
Personal Author:
Staffaroni, Adam M. ; Bajorek, Lynn ; Casaletto, Kaitlin B. ; Cobigo, Yann ; Goh, Sheng-Yang M. ; ... More +
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. Less -
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.


Subject:
[+]
Article
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

Source:
Alzheimers Dement. 16(1):11-21
Pubmed ID:
31914230
Pubmed Central ID:
PMC6842665
Document Type:
Journal Article
Funding:
Biogen/International ; K24 AG045333/AG/NIA NIH HHS/United States ; U24 AG021886/AG/NIA NIH HHS/United States ; P01 AG017586/AG/NIA NIH HHS/United States ; Genentech/International ; ... More +
Biogen/International ; K24 AG045333/AG/NIA NIH HHS/United States ; U24 AG021886/AG/NIA NIH HHS/United States ; P01 AG017586/AG/NIA NIH HHS/United States ; Genentech/International ; Wyeth/International ; P01 AG019724/AG/NIA NIH HHS/United States ; Association for Frontotemporal Degeneration/International ; CIHR/Canada ; U01 AG045390/AG/NIA NIH HHS/United States ; Roche/International ; University of Southern California/International ; P30 AG013854/AG/NIA NIH HHS/United States ; Larry L. Hillblom Foundation/International ; Allergan/International ; K23 AG061253/AG/NIA NIH HHS/United States ; Bristol-Myers Squibb/International ; DOD/International ; Eisai/International ; AbbVie/International ; Janssen Pharmaceuticals/International ; P30 AG062421/AG/NIA NIH HHS/United States ; Pfizer/International ; U19 AG063911/AG/NIA NIH HHS/United States ; U01 AG016976/AG/NIA NIH HHS/United States ; AG045390/NH/NIH HHS/United States ; BrightFocus Foundation/International ; Alzheimer's Association/International ; Merck/International ; GE Healthcare/International ; T32 AG023481/AG/NIA NIH HHS/United States ; Parkinson Foundation/International ; R01 AG032306/AG/NIA NIH HHS/United States ; Michael J. Fox Foundation/International ; Alzheimer's Drug Discovery Foundation/International ; 1510130358/New York State Department of Health/International ; Alzheimer Society of British Columbia/International ; Tau Consortium and Association for Frontotemporal Dementia/International ; HDSA/International ; U54 NS092089/NS/NINDS NIH HHS/United States ; Eli Lilly/International ; NINDS/International ; Avid, and Piramal/International ; CDC/International ; AstraZeneca/International ; Penn Institute on Aging/International Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:4c601b4062d679f2bcdc330bb089b53a0356d87c11b4dc7f18139fa42f1f69b6
File Type:

Supporting Files

• 	nihms-1055072-f0001.gif	gif
  	nihms-1055072-f0001.jpg	jpeg
  	nihms-1055072.nxml	xml
  	NIHMS1055072-supplement-Supplemental_Methods.pdf	pdf
  	NIHMS1055072-supplement-Supplemental_Table_1.docx	docx

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