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Brain functional network integrity sustains cognitive function despite atrophy in presymptomatic genetic frontotemporal dementia.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Tsvetanov, Kamen A.  ORCID logo  https://orcid.org/0000-0002-3178-6363
Gazzina, Stefano 
Jones, P Simon 
van Swieten, John 
Borroni, Barbara 

Abstract

INTRODUCTION: The presymptomatic phase of neurodegenerative disease can last many years, with sustained cognitive function despite progressive atrophy. We investigate this phenomenon in familial frontotemporal dementia (FTD). METHODS: We studied 121 presymptomatic FTD mutation carriers and 134 family members without mutations, using multivariate data-driven approach to link cognitive performance with both structural and functional magnetic resonance imaging. Atrophy and brain network connectivity were compared between groups, in relation to the time from expected symptom onset. RESULTS: There were group differences in brain structure and function, in the absence of differences in cognitive performance. Specifically, we identified behaviorally relevant structural and functional network differences. Structure-function relationships were similar in both groups, but coupling between functional connectivity and cognition was stronger for carriers than for non-carriers, and increased with proximity to the expected onset of disease. DISCUSSION: Our findings suggest that the maintenance of functional network connectivity enables carriers to maintain cognitive performance.

Description

Keywords

frontotemporal dementia (FTD), functional magnetic resonance imaging (fMRI), network connectivity, presymptomatic, Atrophy, Brain, C9orf72 Protein, Cognition, Frontotemporal Dementia, Humans, Internationality, Magnetic Resonance Imaging, Middle Aged, Mutation, Prodromal Symptoms, tau Proteins

Journal Title

Alzheimers Dement

Conference Name

Journal ISSN

1552-5260
1552-5279

Volume Title

17

Publisher

Wiley
Sponsorship
British Academy (pf160048)
Guarantors of Brain (Unknown)
Wellcome Trust (103838/Z/14/Z)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
MRC (unknown)
Medical Research Council (MR/J009482/1)
Medical Research Council (MC_U105597119)
Medical Research Council (MC_UU_00005/12)
K.A.T. is supported by the British Academy Postdoctoral Fellowship (PF160048) and the Guarantors of Brain (101149). J.B.R. is supported by the Wellcome Trust (103838) the Medical Research Council (SUAG/051 G101400) and the Cambridge NIHR Biomedical Research Centre. R. S.-V. is supported by the Instituto de Salud Carlos III and the JPND network PreFrontAls (01ED1512/AC14/0013) and the Fundació Marató de TV3 (20143810). M.M and E.F are supported by the UK Medical Research Council, the Italian Ministry of Health and the Canadian Institutes of Health Research as part of a Centres of Excellence in Neurodegeneration grant, and also a Canadian Institutes of Health Research operating grant (MOP 327387) and funding from the Weston Brain Institute. J.D.R., D.C. and K.M.M. are supported by the NIHR Queen Square Dementia Biomedical Research Unit, the NIHR UCL/H Biomedical Research Centre and the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility. J.D.R. is supported by an MRC Clinician Scientist Fellowship (MR/M008525/1) and has received funding from the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH), the MRC UK GENFI grant (MR/ M023664/1) and The Bluefield Project. F.T. is supported by the Italian Ministry of Health (Grant NET-2011-02346784). L.C.J. and J.V.S. are supported by the Association for Frontotemporal Dementias Research Grant 2009, ZonMw Memorabel project number 733050103 and 733050813, and the Bluefield project. R.G. supported by Italian Ministry of Health, Ricerca Corrente. The Swedish contributors C.G., L.O. and C.A. were supported by grants from JPND Prefrontals Swedish Research Council (VR) 529-2014-7504, Swedish Research Council (VR) 2015- 02926, Swedish Research Council (VR) 2018-02754, Swedish FTD Initiative-Schorling Foundation, Swedish Brain Foundation, Swedish Alzheimer Foundation, Stockholm County Council ALF, Karolinska Institutet Doctoral Funding and StratNeuro, Swedish Demensfonden, during the conduct of the study.
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