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, 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

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.

© 2020 the Alzheimer's Association.

Figures

Figure 1.
Figure 1.
Patterns of atrophy in familial (top; n=31 ) and sporadic (bottom; n=22) bvFTD. The figure represents the result of two-sample t tests compared with age and gender matched healthy controls (N=30). The models control for age, gender, and TIV. T- maps are thresholded at cluster level FWE-corrected p 0.05 (this corresponds to t = 3.24 and k = 1155 in familial, and t = 3.27 and k = 1004 in sporadic).
Figure 2.
Figure 2.
A. Percentage of respondents endorsing each item of the Neuropsychiatric Inventory Questionnaire (NPI-Q). Bars indicate significant comparisons. B-D. Percentage of responders endorsing apathy (lB), disinhibition (C), and changes in appetite (D), by familial group. Asterisks indicate cohort driving effect. E. Distribution of predominant first behavioral feature (% total) reported for f-bvFTD and s-bvFTD. Initial features did not differ between groups.
Figure 3.
Figure 3.
Regression models for motor scores as a function of CDR® plus NACC FTLD SB by cohort. A. PSPRS Total Score. B. UPDRS Total Score. C. Limb Rigidity Item from PSPRS. D. Finger Tap Score from PSPRS.

Source: PubMed

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