Neurodevelopmental effects of genetic frontotemporal dementia in young adult mutation carriers.
E. Finger
(1)
,
R. Malik
(1)
,
M. Bocchetta
(2, 3)
,
K. Coleman
(1)
,
C. Graff
(4, 5)
,
B. Borroni
(6)
,
M. Masellis
(7)
,
R. Laforce
(8)
,
C. V. Greaves
(2)
,
L. L. Russell
(2)
,
R. S. Convery
(2)
,
A. Bouzigues
(2)
,
D. M. Cash
(2)
,
M. Otto
(9)
,
M. Synofzik
(10, 11)
,
J. B. Rowe
(12)
,
D. Galimberti
(13, 14)
,
P. Tiraboschi
(15)
,
R. Bartha
(1)
,
C. Shoesmith
(1)
,
M. C. Tartaglia
(16)
,
J. C. van Swieten
(17)
,
H. Seelaar
(16)
,
L. C. Jiskoo
(16)
,
S. Sorbi
(18, 19)
,
C. R. Butler
(20)
,
A. Gerhard
(21, 22)
,
R. Sanchez-Valle
(23)
,
A. de Mendonça
(24)
,
F. Moreno
(25)
,
R. Vandenberghe
(26)
,
Isabelle Le Ber
(27, 28)
,
J. Levin
(29, 11, 30)
,
Florence Pasquier
(31, 32, 33)
,
I. Santana
(34)
,
J. D. Rohrer
(2)
,
S. Ducharme
(35, 36)
1
UWO -
University of Western Ontario
2 UCL - University College of London [London]
3 Brunel University London [Uxbridge]
4 Karolinska Institutet [Stockholm]
5 KUH - Karolinska University Hospital [Solna, Sweden]
6 UniBs - Università degli Studi di Brescia = University of Brescia
7 University of Toronto
8 CHU de Québec–Université Laval
9 Universitätsklinikum Ulm - University Hospital of Ulm
10 Eberhard Karls Universität Tübingen = University of Tübingen
11 DZNE - German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen
12 CAM - University of Cambridge [UK]
13 UNIMI - Università degli Studi di Milano = University of Milan
14 Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
15 Fondazione IRCCS Istituto Neurologico "Carlo Besta"
16 Toronto Western Hospital
17 Erasmus MC - Erasmus University Medical Center [Rotterdam]
18 UniFI - Università degli Studi di Firenze = University of Florence = Université de Florence
19 Fondazione Don Carlo Gnocchi
20 Imperial College London
21 University of Manchester [Manchester]
22 Universität Duisburg-Essen = University of Duisburg-Essen [Essen]
23 Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
24 ULISBOA - Universidade de Lisboa = University of Lisbon = Université de Lisbonne
25 HUD - Hospital Universitario Donostia [San Sebastian, Spain]
26 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven
27 ICM - Institut du Cerveau = Paris Brain Institute
28 CHU Pitié-Salpêtrière [AP-HP]
29 LMU - Ludwig Maximilian University [Munich] = Ludwig Maximilians Universität München
30 SyNery - Munich Cluster of Systems Neurology
31 LilNCog - Lille Neurosciences & Cognition - U 1172
32 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
33 Excellence Laboratory LabEx DISTALZ
34 Centro Hospitalar e Universitário [Coimbra]
35 McGill University = Université McGill [Montréal, Canada]
36 Douglas Mental Health University Institute [Montréal]
2 UCL - University College of London [London]
3 Brunel University London [Uxbridge]
4 Karolinska Institutet [Stockholm]
5 KUH - Karolinska University Hospital [Solna, Sweden]
6 UniBs - Università degli Studi di Brescia = University of Brescia
7 University of Toronto
8 CHU de Québec–Université Laval
9 Universitätsklinikum Ulm - University Hospital of Ulm
10 Eberhard Karls Universität Tübingen = University of Tübingen
11 DZNE - German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen
12 CAM - University of Cambridge [UK]
13 UNIMI - Università degli Studi di Milano = University of Milan
14 Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
15 Fondazione IRCCS Istituto Neurologico "Carlo Besta"
16 Toronto Western Hospital
17 Erasmus MC - Erasmus University Medical Center [Rotterdam]
18 UniFI - Università degli Studi di Firenze = University of Florence = Université de Florence
19 Fondazione Don Carlo Gnocchi
20 Imperial College London
21 University of Manchester [Manchester]
22 Universität Duisburg-Essen = University of Duisburg-Essen [Essen]
23 Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
24 ULISBOA - Universidade de Lisboa = University of Lisbon = Université de Lisbonne
25 HUD - Hospital Universitario Donostia [San Sebastian, Spain]
26 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven
27 ICM - Institut du Cerveau = Paris Brain Institute
28 CHU Pitié-Salpêtrière [AP-HP]
29 LMU - Ludwig Maximilian University [Munich] = Ludwig Maximilians Universität München
30 SyNery - Munich Cluster of Systems Neurology
31 LilNCog - Lille Neurosciences & Cognition - U 1172
32 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
33 Excellence Laboratory LabEx DISTALZ
34 Centro Hospitalar e Universitário [Coimbra]
35 McGill University = Université McGill [Montréal, Canada]
36 Douglas Mental Health University Institute [Montréal]
Résumé
While frontotemporal dementia has been considered a neurodegenerative disease that starts in mid-life or later, it is now clearly established that cortical and subcortical volume loss is observed more than a decade prior to symptom onset and progresses with ageing. To test the hypothesis that genetic mutations causing frontotemporal dementia have neurodevelopmental consequences, we examined the youngest adults in the GENFI cohort of pre-symptomatic frontotemporal dementia mutation carriers who are between 19 and 30 years of age.
Structural brain differences and improved performance on some cognitive tests were found for MAPT and GRN mutation carriers relative to familial non-carriers, while smaller volumes were observed in C9orf72 repeat expansion carriers at a mean age of 26 years.
The detection of such early differences supports potential advantageous neurodevelopmental consequences of some frontotemporal dementia-causing genetic mutations. These results have implications for the design of therapeutic interventions for frontotemporal dementia. Future studies at younger ages are needed to identify specific early pathophysiologic or compensatory processes that occur during the neurodevelopmental period.