Comparison of sporadic and familial behavioral variant frontotemporal dementia (FTD) in a North American cohort

Hilary W Heuer; P Wang; K Rascovsky; A Wolf; B Appleby; J Bove; Y Bordelon; P Brannelly; D E Brushaber; C Caso; G Coppola; B Dickerson; S Dickinson; K Domoto-Reilly; K Faber; J Ferrall; J Fields; A Fishman; J Fong; T Foroud; L K Forsberg; D Gearhart; B Ghazanfari; N Ghoshal; J Goldman; J Graff-Radford; N Graff-Radford; I Grant; M Grossman; D Haley; G-Y Hsiung; E Huey; D Irwin; D Jones; K Kantarci; A Karydas; D Kaufer; D Kerwin; D Knopman; J Kornak; J H Kramer; R Kraft; W K Kremers; W Kukull; I Litvan; P Ljubenkov; I R Mackenzie; M Maldonado; M Manoochehri; S McGinnis; E McKinley; M F Mendez; B L Miller; C Onyike; A Pantelyat; R Pearlman; L Petrucelli; M Potter; R Rademakers; E M Ramos; K P Rankin; E D Roberson; E Rogalski; P Sengdy; L Shaw; J Syrjanen; M C Tartaglia; N Tatton; J Taylor; A Toga; J Trojanowski; S Weintraub; B Wong; Z Wszolek; B F Boeve; H J Rosen; A L Boxer; ARTFL and LEFFTDS consortia

doi:10.1002/alz.12046

Comparison of sporadic and familial behavioral variant frontotemporal dementia (FTD) in a North American cohort

Alzheimers Dement. 2020 Jan;16(1):60-70. doi: 10.1002/alz.12046.

Authors

Hilary W Heuer¹, P Wang¹, K Rascovsky², A Wolf¹, B Appleby³, J Bove², Y Bordelon⁴, P Brannelly⁵, D E Brushaber⁶, C Caso⁷, G Coppola⁴, B Dickerson⁸, S Dickinson⁹, K Domoto-Reilly⁷, K Faber¹⁰, J Ferrall¹¹, J Fields⁶, A Fishman¹², J Fong¹, T Foroud¹⁰, L K Forsberg⁶, D Gearhart⁶, B Ghazanfari¹³, N Ghoshal¹⁴, J Goldman¹⁵, J Graff-Radford⁶, N Graff-Radford¹⁶, I Grant¹⁷, M Grossman², D Haley¹⁶, G-Y Hsiung¹⁸, E Huey¹⁵, D Irwin², D Jones⁶, K Kantarci⁶, A Karydas¹, D Kaufer¹¹, D Kerwin¹⁹, D Knopman⁶, J Kornak¹, J H Kramer¹, R Kraft⁶, W K Kremers⁶, W Kukull²⁰, I Litvan²¹, P Ljubenkov¹, I R Mackenzie¹⁸, M Maldonado⁴, M Manoochehri¹⁵, S McGinnis⁸, E McKinley²², M F Mendez⁴, B L Miller¹, C Onyike¹², A Pantelyat¹², R Pearlman²³, L Petrucelli¹⁶, M Potter¹⁰, R Rademakers¹⁶, E M Ramos⁴, K P Rankin¹, E D Roberson²², E Rogalski¹⁷, P Sengdy¹⁸, L Shaw², J Syrjanen⁶, M C Tartaglia¹³, N Tatton⁹, J Taylor¹, A Toga²⁴, J Trojanowski³, S Weintraub¹⁷, B Wong⁸, Z Wszolek¹⁶, B F Boeve⁶, H J Rosen¹, A L Boxer¹; ARTFL and LEFFTDS consortia

Affiliations

¹ University of California, San Francisco, San Francisco, California.
² University of Pennsylvania, Philadelphia, Pennsylvania.
³ Case Western Reserve University, Cleveland, Ohio.
⁴ University of California, Los Angeles, Los Angeles, California.
⁵ Tau Consortium, Rainwater Charitable Foundation, Fort Worth, Texas.
⁶ Mayo Clinic, Rochester, Minnesota.
⁷ U Washington, Seattle, Washington.
⁸ Harvard University/MGH, Boston, Massachusetts.
⁹ Association for Frontotemporal Degeneration, Radnor, Pennsylvania.
¹⁰ National Centralized Repository for Alzheimer's Disease and Related Disorders (NCRAD), Indiana University, Indianapolis, Indiana.
¹¹ University of North Carolina, Chapel Hill, North Carolina.
¹² Johns Hopkins University, Baltimore, Maryland.
¹³ University of Toronto, Toronto, Ontario, Canada.
¹⁴ Washington University, St. Louis, Missouri.
¹⁵ Columbia University, New York, New York.
¹⁶ Mayo Clinic, Jacksonville, Florida.
¹⁷ Northwestern University, Chicago, Illinois.
¹⁸ University of British Columbia, Vancouver, British Columbia, Canada.
¹⁹ The University of Texas, Southwestern Medical Center at Dallas, Dallas, Texas.
²⁰ National Alzheimer Coordinating Center (NACC), University of Washington, Seattle, Washington.
²¹ University of California, San Diego, San Diego, California.
²² University of Alabama at Birmingham, Birmingham, Alabama.
²³ Bluefield Project, San Francisco, California.
²⁴ Laboratory of Neuroimaging (LONI), USC, Los Angeles, California.

Abstract

Introduction: Behavioral variant frontotemporal dementia (bvFTD) may present sporadically or due to an autosomal dominant mutation. Characterization of both forms will improve understanding of the generalizability of assessments and treatments.

Methods: A total of 135 sporadic (s-bvFTD; mean age 63.3 years; 34% female) and 99 familial (f-bvFTD; mean age 59.9; 48% female) bvFTD participants were identified. f-bvFTD cases included 43 with known or presumed chromosome 9 open reading frame 72 (C9orf72) gene expansions, 28 with known or presumed microtubule-associated protein tau (MAPT) mutations, 14 with known progranulin (GRN) mutations, and 14 with a strong family history of FTD but no identified mutation.

Results: Participants with f-bvFTD were younger and had earlier age at onset. s-bvFTD had higher total Neuropsychiatric Inventory Questionnaire (NPI-Q) scores due to more frequent endorsement of depression and irritability.

Discussion: f-bvFTD and s-bvFTD cases are clinically similar, suggesting the generalizability of novel biomarkers, therapies, and clinical tools developed in either form to the other.

Keywords: C9orf72; GRN; MAPT; bvFTD; clinical trials; frontotemporal dementia; genetics.

Publication types

Comparative Study
Research Support, N.I.H., Extramural

MeSH terms

Age Factors
Aged
Brain / pathology
C9orf72 Protein / genetics
Female
Frontotemporal Dementia* / classification
Frontotemporal Dementia* / genetics
Genetic Predisposition to Disease*
Humans
Male
Middle Aged
Mutation / genetics*
Neuropsychological Tests / statistics & numerical data*
North America
Progranulins / genetics
tau Proteins / genetics

Substances

C9orf72 Protein
C9orf72 protein, human
GRN protein, human
MAPT protein, human
Progranulins
tau Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding