Assessment of executive function declines in presymptomatic and mildly symptomatic familial frontotemporal dementia: NIH-EXAMINER as a potential clinical trial endpoint.
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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, ARTFL/LEFFTDS consortium
Аннотация
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.