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

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

Hilary W Heuer  1 , P Wang  1 , K Rascovsky  2 , A Wolf  1 , B Appleby  3 , J Bove  2 , Y Bordelon  4 , P Brannelly  5 , D E Brushaber  6 , C Caso  7 , G Coppola  4 , B Dickerson  8 , S Dickinson  9 , K Domoto-Reilly  7 , K Faber  10 , J Ferrall  11 , J Fields  6 , A Fishman  12 , J Fong  1 , T Foroud  10 , L K Forsberg  6 , D Gearhart  6 , B Ghazanfari  13 , N Ghoshal  14 , J Goldman  15 , J Graff-Radford  6 , N Graff-Radford  16 , I Grant  17 , M Grossman  2 , D Haley  16 , G-Y Hsiung  18 , E Huey  15 , D Irwin  2 , D Jones  6 , K Kantarci  6 , A Karydas  1 , D Kaufer  11 , D Kerwin  19 , D Knopman  6 , J Kornak  1 , J H Kramer  1 , R Kraft  6 , W K Kremers  6 , W Kukull  20 , I Litvan  21 , P Ljubenkov  1 , I R Mackenzie  18 , M Maldonado  4 , M Manoochehri  15 , S McGinnis  8 , E McKinley  22 , M F Mendez  4 , B L Miller  1 , C Onyike  12 , A Pantelyat  12 , R Pearlman  23 , L Petrucelli  16 , M Potter  10 , R Rademakers  16 , E M Ramos  4 , K P Rankin  1 , E D Roberson  22 , E Rogalski  17 , P Sengdy  18 , L Shaw  2 , J Syrjanen  6 , M C Tartaglia  13 , N Tatton  9 , J Taylor  1 , A Toga  24 , J Trojanowski  3 , S Weintraub  17 , B Wong  8 , Z Wszolek  16 , B F Boeve  6 , H J Rosen  1 , A L Boxer  1 ; ARTFL and LEFFTDS consortia
Affiliations
Comparative Study

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

Hilary W Heuer et al. Alzheimers Dement. 2020 Jan.

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.

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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.
See this image and copyright information in PMC

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