期刊
NEUROIMAGE-CLINICAL
卷 26, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.nicl.2020.102210
关键词
Frontotemporal dementia; MRI, Basal forebrain; Volumetry
类别
资金
- Alzheimer's Research UK
- Brain Research Trust
- Wolfson Foundation
- NIHR Queen Square Dementia Biomedical Research Unit
- NIHR UCL/H Biomedical Research Centre
- Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility
- Alzheimer's Society [AS-PG-16007]
- MRC UK GENFI grant [MR/M023664/1]
- MRC Clinician Scientist Fellowship [MR/M008525/1]
- NIHR Rare Disease Translational Research Collaboration [BRC149/NS/MH]
- Alzheimer's Society
- NIHR UCL/UCLH Biomedical Research Centre
- Medical Research Council UK GENFI grant [MR/M023664/1]
- MRC [MR/M008525/1, MR/M023664/1, MR/J009482/1] Funding Source: UKRI
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 Picks 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%), Picks 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.
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