Differential early subcortical involvement in genetic FTD within the GENFI cohort

被引：38

作者：

Bocchetta, Martina ^{[1
]}

Todd, Emily G. ^{[1
]}

Peakman, Georgia ^{[1
]}

Cash, David M. ^{[1
,2
]}

Convery, Rhian S. ^{[1
]}

Russell, Lucy L. ^{[1
]}

Thomas, David L. ^{[1
,3
]}

Iglesias, Juan Eugenio ^{[2
,4
,5
,6
]}

van Swieten, John C. ^{[7
,8
]}

Jiskoot, Lize C. ^{[7
,8
]}

Seelaar, Harro ^{[7
,8
]}

Borroni, Barbara ^{[9
]}

Galimberti, Daniela ^{[10
,11
]}

Sanchez-Valle, Raquel ^{[12
]}

Laforce, Robert ^{[13
]}

Moreno, Fermin ^{[14
]}

Synofzik, Matthis ^{[15
]}

Graff, Caroline ^{[16
,17
]}

Masellis, Mario ^{[18
]}

Tartaglia, Maria Carmela ^{[19
]}

Rowe, James B. ^{[20
,21
,22
]}

Vandenberghe, Rik ^{[23
]}

Finger, Elizabeth ^{[24
]}

Tagliavini, Fabrizio ^{[25
]}

de Mendonca, Alexandre ^{[26
]}

Santana, Isabel ^{[27
]}

Butler, Chris R. ^{[28
]}

Ducharme, Simon ^{[29
]}

Gerhard, Alexander ^{[30
,31
,32
]}

Danek, Adrian ^{[33
,34
,35
]}

Levin, Johannes ^{[33
,34
,35
]}

Otto, Markus ^{[36
]}

Sorbi, Sandro ^{[37
]}

Le Ber, Isabelle ^{[38
,39
,40
]}

Pasquier, Florence ^{[41
,42
,43
]}

Rohrer, Jonathan D. ^{[1
]}

机构：

[1] UCL, UCL Queen Sq Inst Neurol, Dept Neurodegenerat Dis, Dementia Res Ctr, London, England

[2] UCL, Dept Med Phys & Biomed Engn, Ctr Med Image Comp, London, England

[3] UCL, UCL Queen Sq Inst Neurol, Neuroradiol Acad Unit, London, England

[4] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA

[5] Harvard Med Sch, Boston, MA 02115 USA

[6] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA

[7] Erasmus MC, Dept Neurol, Rotterdam, Netherlands

[8] Erasmus MC, Alzheimer Ctr, Rotterdam, Netherlands

[9] Univ Brescia, Dept Clin & Expt Sci, Neurol Unit, Ctr Neurodegenerat Disorders, Brescia, Italy

[10] Univ Milan, Dept Biomed Surg & Dent Sci, Milan, Italy

[11] Osped Maggiore Policlin, Fdn IRCCS CaGranda, Milan, Italy

[12] Inst Invest Biomed, Hosp Clin, Neurol Dept, Barcelona, Spain

[13] Univ Laval, Fac Med, CHU Quebec, Clin Interdisciplinaire Memoire,Dept Sci Neurol, Quebec City, PQ, Canada

[14] Hosp Univ Donostia, San Sebastian, Spain

[15] Hertie Inst Clin Brain Res, Ctr Neurol, Dept Cognit Neurol, Tubingen, Germany

[16] Karolinska Inst, Dept NVS, Div Neurogeriatr, Stockholm, Sweden

[17] Karolinska Univ Hosp Solna, Theme Aging, Unit Hereditray Dementia, Stockholm, Sweden

[18] Sunnybrook Res Inst, Campbell Cognit Neurol Res Unit, Toronto, ON, Canada

[19] Toronto Western Hosp, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON, Canada

[20] Univ Cambridge, Dept Clin Neurosci, Cambridge, England

[21] Univ Cambridge, Cambridge Univ Hosp NHS Trust, Cambridge, England

[22] Univ Cambridge, MRC, Cognit & Brain Sci Unit, Cambridge, England

[23] Katholieke Univ Leuven, Dept Neurosci, Lab Cognit Neurol, Leuven, Belgium

[24] Univ Western Ontario, Dept Clin Neurol Sci, London, ON, Canada

[25] Fdn Ist Ricovero & Cura Carattere Sci, Ist Neurol Carlo Besta, Milan, Italy

[26] Univ Lisbon, Fac Med, Lisbon, Portugal

[27] Ctr Hosp & Univ Coimbra, Neurol Dept, Coimbra, Portugal

[28] Univ Oxford, Dept Clin Neurol, Oxford, England

[29] McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ, Canada

[30] Univ Manchester, Wolfson Mol Imaging Ctr, Div Neurosci & Expt Psychol, Manchester, Lancs, England

[31] Univ Duisburg Essen, Dept Geriatr Med, Essen, Germany

[32] Univ Duisburg Essen, Dept Nucl Med, Essen, Germany

[33] Ludwig Maximilians Univ Munchen, Neurol Klin & Poliklin, Munich, Germany

[34] German Ctr Neurodegenerat Dis DZNE, Munich, Germany

[35] Munich Cluster Syst Neurol, Munich, Germany

[36] Univ Hosp Ulm, Dept Neurol, Ulm, Germany

[37] Univ Florence, Dept Neurosci Psychol Drug Res & Child Hlth, Florence, Italy

[38] Sorbonne Univ, Hop Pitie Salpetriere, AP HP,CNRS,UMR 7225, Paris Brain Inst,Inst Cerveau ICM,Inserm U1127, Paris, France

[39] Hop La Pitie Salpetriere, AP HP, IM2A, Ctr Dereerence Demences Rares Precoces,Dept Neuro, Paris, France

[40] Hop La Pitie Salpetriere, AP HP, Dept Neurol, Paris, France

[41] Univ Lille, Lille, France

[42] Inserm 1172 Lille, Lille, France

[43] CHU, LiCENDLille, CNR MAJ, Labex Distalz, Lille, France

来源：

NEUROIMAGE-CLINICAL | 2021年 / 30卷

关键词：

Genetic frontotemporal dementia; MRI imaging; Brain volumetry; Presymptomatic stage; FRONTOTEMPORAL DEMENTIA; C9ORF72; MUTATION; BRAIN ATROPHY; SEGMENTATION; DEGENERATION; TAU; NEUROPATHOLOGY; PROGRANULIN; PATHOLOGY; PATHWAYS;

D O I：

10.1016/j.nicl.2021.102646

中图分类号：

R445 [影像诊断学];

学科分类号：

100207 ;

摘要：

Background: Studies have previously shown evidence for presymptomatic cortical atrophy in genetic FTD. Whilst initial investigations have also identified early deep grey matter volume loss, little is known about the extent of subcortical involvement, particularly within subregions, and how this differs between genetic groups. Methods: 480 mutation carriers from the Genetic FTD Initiative (GENFI) were included (198 GRN, 202 C9orf72, 80 MAPT), together with 298 non-carrier cognitively normal controls. Cortical and subcortical volumes of interest were generated using automated parcellation methods on volumetric 3 T T1-weighted MRI scans. Mutation carriers were divided into three disease stages based on their global CDR (R) plus NACC FTLD score: asymptomatic (0), possibly or mildly symptomatic (0.5) and fully symptomatic (1 or more). Results: In all three groups, subcortical involvement was seen at the CDR 0.5 stage prior to phenoconversion, whereas in the C9orf72 and MAPT mutation carriers there was also involvement at the CDR 0 stage. In the C9orf72 expansion carriers the earliest volume changes were in thalamic subnuclei (particularly pulvinar and lateral geniculate, 9-10%) cerebellum (lobules VIIa-Crus II and VIIIb, 2-3%), hippocampus (particularly presubiculum and CA1, 2-3%), amygdala (all subregions, 2-6%) and hypothalamus (superior tuberal region, 1%). In MAPT mutation carriers changes were seen at CDR 0 in the hippocampus (subiculum, presubiculum and tail, 3-4%) and amygdala (accessory basal and superficial nuclei, 2-4%). GRN mutation carriers showed subcortical differences at CDR 0.5 in the presubiculum of the hippocampus (8%). Conclusions: C9orf72 expansion carriers show the earliest and most widespread changes including the thalamus, basal ganglia and medial temporal lobe. By investigating individual subregions, changes can also be seen at CDR 0 in MAPT mutation carriers within the limbic system. Our results suggest that subcortical brain volumes may be used as markers of neurodegeneration even prior to the onset of prodromal symptoms.

引用

页数：9

共 48 条

[11] Patterns of gray matter atrophy in genetic frontotemporal dementia: results from the GENFI study
Cash, David M.
Bocchetta, Martina
Thomas, David L.
Dick, Katrina M.
van Swieten, John C.
Borroni, Barbara
Galimberti, Daniela
Masellis, Mario
Tartaglia, Maria Carmela
Rowe, James B.
Graff, Caroline
Tagliavini, Fabrizio
Frisoni, Giovanni B.
Laforce, Robert, Jr.
Finger, Elizabeth
de Mendonca, Alexandre
Sorbi, Sandro
Rossor, Martin N.
Ourselin, Sebastien
Rohrer, Jonathan D.
[J]. NEUROBIOLOGY OF AGING, 2018, 62 : 191 - 196
[12] Imaging Biomarkers for Neurodegeneration in Presymptomatic Familial Frontotemporal Lobar Degeneration
Chen, Qin
Kantarci, Kejal
[J]. FRONTIERS IN NEUROLOGY, 2020, 11
[13] Abnormal pain perception is associated with thalamo-cortico-striatal atrophy in C9orf72 expansion carriers in the GENFI cohort
Convery, Rhian S.
Bocchetta, Martina
Greaves, Caroline, V
Moore, Katrina M.
Cash, David M.
Van Swieten, John
Moreno, Fermin
Sanchez-Valle, Raquel
Borroni, Barbara
Laforce, Robert, Jr.
Masellis, Mario
Tartaglia, Maria Carmela
Graff, Caroline
Galimberti, Daniela
Rowe, James B.
Finger, Elizabeth
Synofzik, Matthis
Vandenberghe, Rik
de Mendonca, Alexandre
Tagliavini, Fabrizio
Santana, Isabel
Ducharme, Simon
Butler, Christopher
Gerhard, Alex
Levin, Johannes
Danek, Adrian
Otto, Markus
Warren, Jason D.
Rohrer, Jonathan D.
[J]. JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 2020, 91 (12) : 1325 - 1328
[14] Basal forebrain atrophy in frontotemporal dementia
Convery, Rhian S.
Neason, Mollie R.
Cash, David M.
Cardoso, M. Jorge
Modat, Marc
Ourselin, Sebastien
Warren, Jason D.
Rohrer, Jonathan D.
Bocchetta, Martina
[J]. NEUROIMAGE-CLINICAL, 2020, 26
[15] Hippocampal Sclerosis but Not Normal Aging or Alzheimer Disease Is Associated With TDP-43 Pathology in the Basal Forebrain of Aged Persons
Cykowski, Matthew D.
Takei, Hidehiro
Van Eldik, Linda J.
Schmitt, Frederick A.
Jicha, Gregory A.
Powell, Suzanne Z.
Nelson, Peter T.
[J]. JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2016, 75 (05) : 397 - 407
[16] Seeking a unified framework for cerebellar function and dysfunction: from circuit operations to cognition
D'Angelo, Egidio
Casali, Stefano
[J]. FRONTIERS IN NEURAL CIRCUITS, 2013, 6
[17] Intrinsic Connectivity of Hippocampal Subfields in Normal Elderly and Mild Cognitive Impairment Patients
de Flores, Robin
Mutlu, Justine
Bejanin, Alexandre
Gonneaud, Julie
Landeau, Brigitte
Tomadesso, Clemence
Mezenge, Florence
de La Sayette, Vincent
Eustache, Francis
Chetelat, Gael
[J]. HUMAN BRAIN MAPPING, 2017, 38 (10) : 4922 - 4932
[18] Imaging the deep cerebellar nuclei: A probabilistic atlas and normalization procedure
Diedrichsen, J.
Maderwald, S.
Kueper, M.
Thuerling, M.
Rabe, K.
Gizewski, E. R.
Ladd, M. E.
Timmann, D.
[J]. NEUROIMAGE, 2011, 54 (03) : 1786 - 1794
[19] A probabilistic MR atlas of the human cerebellum
Diedrichsen, Joern
Balsters, Joshua H.
Flavell, Jonathan
Cussans, Emma
Ramnani, Narender
[J]. NEUROIMAGE, 2009, 46 (01) : 39 - 46
[20] Psychiatric Presentations of C9orf72 Mutation: What Are the Diagnostic Implications for Clinicians?
Ducharme, Simon
Bajestan, Sepideh
Dickerson, Bradford C.
Voon, Valerie
[J]. JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES, 2017, 29 (03) : 195 - 205

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