Clinical and volumetric changes with increasing functional impairment in familial frontotemporal lobar degeneration

Nicholas T Olney, Elise Ong, Sheng-Yang M Goh, Lynn Bajorek, Reilly Dever, Adam M Staffaroni, Yann Cobigo, Meredith Bock, Kevin Chiang, Peter Ljubenkov, John Kornak, Hilary W Heuer, Ping Wang, Katya Rascovsky, Amelia Wolf, Brian Appleby, Jessica Bove, Yvette Bordelon, Patrick Brannelly, Danielle Brushaber, Christine Caso, Giovanni Coppola, Bradford C Dickerson, Susan Dickinson, Kimiko Domoto-Reilly, Kelly Faber, Jessica Ferrall, Julie Fields, Ann Fishman, Jamie Fong, Tatiana Foroud, Leah K Forsberg, Debra J Gearhart, Behnaz Ghazanfari, Nupur Ghoshal, Jill Goldman, Jonathan Graff-Radford, Neill R Graff-Radford, Ian Grant, Murray Grossman, Dana Haley, Gingyuek Hsiung, Edward D Huey, David J Irwin, David T Jones, Kejal Kantarci, Anna M Karydas, Daniel Kaufer, Diana Kerwin, David S Knopman, Joel H Kramer, Ruth Kraft, Walter Kremers, Walter Kukull, Maria I Lapid, Irene Litvan, Ian R Mackenzie, Miranda Maldonado, Masood Manoochehri, Scott M McGinnis, Emily C McKinley, Mario F Mendez, Bruce L Miller, Chiadi Onyike, Alex Pantelyat, Rodney Pearlman, Len Petrucelli, Madeleine Potter, Rosa Rademakers, Eliana M Ramos, Katherine P Rankin, Erik D Roberson, Emily Rogalski, Pheth Sengdy, Leslie M Shaw, Jeremy Syrjanen, M Carmela Tartaglia, Nadine Tatton, Joanne Taylor, Arthur Toga, John Q Trojanowski, Sandra Weintraub, Bonnie Wong, Zbigniew Wszolek, Adam L Boxer, Brad F Boeve, Howard J Rosen, ARTFL and LEFFTDS consortia, Nicholas T Olney, Elise Ong, Sheng-Yang M Goh, Lynn Bajorek, Reilly Dever, Adam M Staffaroni, Yann Cobigo, Meredith Bock, Kevin Chiang, Peter Ljubenkov, John Kornak, Hilary W Heuer, Ping Wang, Katya Rascovsky, Amelia Wolf, Brian Appleby, Jessica Bove, Yvette Bordelon, Patrick Brannelly, Danielle Brushaber, Christine Caso, Giovanni Coppola, Bradford C Dickerson, Susan Dickinson, Kimiko Domoto-Reilly, Kelly Faber, Jessica Ferrall, Julie Fields, Ann Fishman, Jamie Fong, Tatiana Foroud, Leah K Forsberg, Debra J Gearhart, Behnaz Ghazanfari, Nupur Ghoshal, Jill Goldman, Jonathan Graff-Radford, Neill R Graff-Radford, Ian Grant, Murray Grossman, Dana Haley, Gingyuek Hsiung, Edward D Huey, David J Irwin, David T Jones, Kejal Kantarci, Anna M Karydas, Daniel Kaufer, Diana Kerwin, David S Knopman, Joel H Kramer, Ruth Kraft, Walter Kremers, Walter Kukull, Maria I Lapid, Irene Litvan, Ian R Mackenzie, Miranda Maldonado, Masood Manoochehri, Scott M McGinnis, Emily C McKinley, Mario F Mendez, Bruce L Miller, Chiadi Onyike, Alex Pantelyat, Rodney Pearlman, Len Petrucelli, Madeleine Potter, Rosa Rademakers, Eliana M Ramos, Katherine P Rankin, Erik D Roberson, Emily Rogalski, Pheth Sengdy, Leslie M Shaw, Jeremy Syrjanen, M Carmela Tartaglia, Nadine Tatton, Joanne Taylor, Arthur Toga, John Q Trojanowski, Sandra Weintraub, Bonnie Wong, Zbigniew Wszolek, Adam L Boxer, Brad F Boeve, Howard J Rosen, ARTFL and LEFFTDS consortia

Abstract

Introduction: The Advancing Research and Treatment in Frontotemporal Lobar Degeneration and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects longitudinal studies were designed to describe the natural history of familial-frontotemporal lobar degeneration due to autosomal dominant mutations.

Methods: We examined cognitive performance, behavioral ratings, and brain volumes from the first time point in 320 MAPT, GRN, and C9orf72 family members, including 102 non-mutation carriers, 103 asymptomatic carriers, 43 mildly/questionably symptomatic carriers, and 72 carriers with dementia.

Results: Asymptomatic carriers showed similar scores on all clinical measures compared with noncarriers but reduced frontal and temporal volumes. Those with mild/questionable impairment showed decreased verbal recall, fluency, and Trail Making Test performance and impaired mood and self-monitoring. Dementia was associated with impairment in all measures. All MAPT carriers with dementia showed temporal atrophy, but otherwise, there was no single cognitive test or brain region that was abnormal in all subjects.

Discussion: Imaging changes appear to precede clinical changes in familial-frontotemporal lobar degeneration, but specific early clinical and imaging changes vary across individuals.

Keywords: C9ORF72; Familial; Frontotemporal lobar degeneration; GRN; Genetic; MAPT.

© 2019 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.

Figures

Fig. 1.
Fig. 1.
Proportion of individuals in each group with abnormal performance (z

Fig. 2.

Proportion of individuals in each…

Fig. 2.

Proportion of individuals in each group with reduced gray matter volume (w-score

Fig. 2.
Proportion of individuals in each group with reduced gray matter volume (w-score
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Fig. 2.
Fig. 2.
Proportion of individuals in each group with reduced gray matter volume (w-score

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