O4‐03‐01: Frontotemporal Lobar Degeneration Research in North America: Progress in the Artfl/lefftds Consortia
Year: 2019
Type: article
Abstract: Two NIH-funded research consortia have been designed to identify clinical trial cohorts, investigate disease progression, and develop new clinical trial outcome measures in frontotemporal lobar degeneration (FTLD). The Advancement of Research and Treatment in FTLD (ARTFL) protocol involves 18 clinical centers that evaluate participants with sporadic and familial FTLD. The 8-site Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS) protocol co-enrolls ARTFL participants from kindreds with mutations in microtubule associated protein tau (MAPT), progranulin (GRN), or chromosome 9 open reading frame 72 (C9orf72). An integrated infrastructure was created for the two consortia with common procedures. Participants with FTLD spectrum disorders (bvFTD, svPPA, nfvPPA, FTD-ALS, CBS or PSP) or with strong family histories of FTLD undergo clinical and neuropsychological evaluations and blood draws for genetic and biomarker analyses; lumbar puncture for CSF collection is optional. Familial participants return for yearly follow-up visits (ARTFL: 1 follow-up visit; LEFFTDS 3 follow-up visits). All participants are genotyped for dementia-associated mutations. To date, 1244 participants enrolled in ARTFL and LEFFTDS have undergone baseline assessment: 616 (49.5%) female, 1140 (91.6%) Caucasian, mean age 56 (range 18-89) years, and mean education 16 (range 11-22) years. The most common diagnoses in the sporadic cohort are bvFTD (30%) and PSP (21%), followed by CBS (13%), svPPA (12%), nfvPPA (10%), and FTD-ALS (4%). Of 586 familial participants, 25% have a MAPT mutation in the kindred, 20% have a GRN mutation in the kindred, 34% have the C9orf72 expansion in the kindred, and 4 individuals have a double familial mutation in C9orf72 and GRN. 16% of familial participants lacked known mutations, and a small number had other FTD-associated mutations. Annual follow-up evaluations for participants in the LEFFTDS study have been completed in 278 (71%) for Visit 2, 162 (41%) for Visit 3, and 35 (9%) for Visit 4. Blood samples are currently available from 1023 individuals and MRIs from 612 participants. These integrated consortia are actively evaluating participants across North America to characterize FTLD and prepare sites and investigators for FTLD clinical trials. Clinical, genetic, and imaging data and biospecimens are available to investigators worldwide.
Source: Alzheimer s & Dementia
Authors: Hilary W. Heuer, Adam L. Boxer, Bradley F. Boeve, Howard J. Rosen, Leah K. Forsberg, Danielle Brushaber, Brian Appleby, Yvette M. Bordelon, Patrick Brannelly, Giovanni Coppola, Brad C. Dickerson, Susan Dickinson, Domoto-Reilly Kimiko, Kelley Faber, Julie A. Fields, Jamie Fong, Tatiana M. Foroud, Ralitza H. Gavrilova, Nupur Ghoshal, Jill Goldman, Jonathan Graff-Radford, Neil R. Graff-Radford, Ian Grant, Murray Grossman, John Hsiao, Ging-Yuek Robin Hsiung, Edward Huey, David Irwin, Kejal Kantarci, Anna M. Karydas, Daniel Kaufer, Diana R. Kerwin, David S. Knopman, Joel H. Kramer, Walter K. Kremers, Walter A. Kukull, Irene Litvan, Peter A. Ljubenkov, Diane E. Lucente, Codrin Lungu, Ian R. Mackenzie, Scott M. McGinnis, Mario F. Mendez, Bruce L. Miller, Chiadi U. Onyike, Alex Pantelyat, Rodney Pearlman, Leonard Petrucelli, Rosa Rademakers, Eliana Marisa Ramos, Katherine Rankin, Katya Rascovsky, Erik D. Roberson, Emily J. Rogalski, Leslie M. Shaw, Margaret Sutherland, Jeremy Syrjanen, Carmela Tartaglia, Nadine Tatton, Joanne Taylor, Arthur W. Toga, Sandra Weintraub, Bonnie Wong, Zbigniew Wszolek, ARTFL and LEFFTDS Consortia
Institutions: University of California, San Francisco, Mayo Clinic, Case Western Reserve University, University of California, Los Angeles, Rainwater Charitable Foundation, Massachusetts General Hospital, Association for Frontotemporal Degeneration, University of Washington Medical Center, Indiana University School of Medicine, Washington University in St. Louis, Columbia University, Mayo Clinic in Florida, Northwestern University, University of Pennsylvania, National Institutes of Health, University of British Columbia, University of Pennsylvania Health System, University of North Carolina at Chapel Hill, The University of Texas Southwestern Medical Center, University of Washington, National Alzheimer's Coordinating Center, University of California San Diego, Johns Hopkins University, University of Alabama at Birmingham, University of Toronto, University of Southern California
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2980698963