Basal forebrain atrophy in frontotemporal dementia

Rhian S Convery; Mollie R Neason; David M Cash; M Jorge Cardoso; Marc Modat; Sebastien Ourselin; Jason D Warren; Jonathan D Rohrer; Martina Bocchetta

doi:10.1016/j.nicl.2020.102210

Basal forebrain atrophy in frontotemporal dementia

Neuroimage Clin. 2020:26:102210. doi: 10.1016/j.nicl.2020.102210. Epub 2020 Feb 13.

Authors

Rhian S Convery¹, Mollie R Neason¹, David M Cash², M Jorge Cardoso³, Marc Modat³, Sebastien Ourselin³, Jason D Warren¹, Jonathan D Rohrer⁴, Martina Bocchetta⁵

Affiliations

¹ Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom.
² Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom; Centre for Medical Image Computing, Department of Medical Physics and Biomedical Engineering, University College London, London, United Kingdom.
³ School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom.
⁴ Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom. Electronic address: j.rohrer@ucl.ac.uk.
⁵ Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom. Electronic address: m.bocchetta@ucl.ac.uk.

Abstract

Background: The basal forebrain is a subcortical structure that plays an important role in learning, attention, and memory. Despite the known subcortical involvement in frontotemporal dementia (FTD), there is little research into the role of the basal forebrain in this disease. We aimed to investigate differences in basal forebrain volumes between clinical, genetic, and pathological diagnoses of FTD.

Methods: 356 patients with FTD were recruited from the UCL Dementia Research Centre and matched on age and gender with 83 cognitively normal controls. All subjects had a T1-weighted MR scan suitable for analysis. Basal forebrain volumes were calculated using the Geodesic Information Flow (GIF) parcellation method and were compared between clinical (148 bvFTD, 82 svPPA, 103 nfvPPA, 14 PPA-NOS, 9 FTD-MND), genetic (24 MAPT, 15 GRN, 26 C9orf72) and pathological groups (28 tau, 3 FUS, 35 TDP-43) and controls. A subanalysis was also performed comparing pathological subgroups of tau (11 Pick's disease, 6 FTDP-17, 7 CBD, 4 PSP) and TDP-43 (12 type A, 2 type B, 21 type C).

Results: All clinical subtypes of FTD showed significantly smaller volumes than controls (p ≤ 0.010, ANCOVA), with svPPA (10% volumetric difference) and bvFTD (9%) displaying the smallest volumes. Reduced basal forebrain volumes were also seen in MAPT mutations (18%, p < 0.0005) and in individuals with pathologically confirmed FTDP-17 (17%), Pick's disease (12%), and TDP-43 type C (8%) (p < 0.001).

Conclusion: Involvement of the basal forebrain is a common feature in FTD, although the extent of volume reduction differs between clinical, genetic, and pathological diagnoses. Tauopathies, particularly those with MAPT mutations, had the smallest volumes. However, atrophy was also seen in those with TDP-43 type C pathology (most of whom have svPPA clinically). This suggests that the basal forebrain is vulnerable to multiple types of FTD-associated protein inclusions.

Keywords: Frontotemporal dementia; MRI, Basal forebrain; Volumetry.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Atrophy / pathology*
Basal Forebrain / pathology*
Female
Frontotemporal Dementia / pathology*
Humans
Magnetic Resonance Imaging
Male
Middle Aged

Abstract

Publication types

MeSH terms

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