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

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.

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

Published Date:

Jan 2020

Source:

Alzheimers Dement. 16(1):11-21

Language:

English

Public Access Version Available on: January 01, 2021, 12:00 AM

Please check back on the date listed above.

Details:

Alternative Title:

Alzheimers Dement

Personal Author:

Staffaroni, Adam M. ; Bajorek, Lynn ; Casaletto, Kaitlin B. ; Cobigo, Yann ; Goh, Sheng-Yang M. ; ... More ▼

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:

[+]

Pubmed ID:

31914230

Pubmed Central ID:

PMC6842665

Document Type:

Journal Article

Funding:

AG045390/NH/NIH HHS/United States ; Larry L. Hillblom Foundation/ ; CDC/ ; Bristol-Myers Squibb/ ; Eli Lilly/ ; ... More ▼

Collection(s):

CDC Public Access

Main Document Checksum:

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Supporting Files:

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