TY  - JOUR
JF  - NeuroImage: Clinical
KW  - CI
KW  -  Confidence interval
KW  -  FTD
KW  -  Frontotemporal dementia
KW  -  IQR
KW  -  Inter Quartile Range
KW  -  PS
KW  -  Presymptomatic
KW  -  S
KW  -  Symptomatic
KW  -  TIV
KW  -  Total Intracranial volume
KW  -  WMH
KW  -  White matter hyperintensity
A1  - Sudre, CH
A1  - Bocchetta, M
A1  - Cash, D
A1  - Thomas, DL
A1  - Woollacott, I
A1  - Dick, KM
A1  - van Swieten, J
A1  - Borroni, B
A1  - Galimberti, D
A1  - Masellis, M
A1  - Tartaglia, MC
A1  - Rowe, JB
A1  - Graff, C
A1  - Tagliavini, F
A1  - Frisoni, G
A1  - Laforce, R
A1  - Finger, E
A1  - de Mendonça, A
A1  - Sorbi, S
A1  - Ourselin, S
A1  - Cardoso, MJ
A1  - Rohrer, JD
A1  - Genetic FTD Initiative, GENFI, .
ID  - discovery1554909
N2  - Genetic frontotemporal dementia is most commonly caused by mutations in the progranulin (GRN), microtubule-associated protein tau (MAPT) and chromosome 9 open reading frame 72 (C9orf72) genes. Previous small studies have reported the presence of cerebral white matter hyperintensities (WMH) in genetic FTD but this has not been systematically studied across the different mutations. In this study WMH were assessed in 180 participants from the Genetic FTD Initiative (GENFI) with 3D T1- and T2-weighed magnetic resonance images: 43 symptomatic (7 GRN, 13 MAPT and 23 C9orf72), 61 presymptomatic mutation carriers (25 GRN, 8 MAPT and 28 C9orf72) and 76 mutation negative non-carrier family members. An automatic detection and quantification algorithm was developed for determining load, location and appearance of WMH. Significant differences were seen only in the symptomatic GRN group compared with the other groups with no differences in the MAPT or C9orf72 groups: increased global load of WMH was seen, with WMH located in the frontal and occipital lobes more so than the parietal lobes, and nearer to the ventricles rather than juxtacortical. Although no differences were seen in the presymptomatic group as a whole, in the GRN cohort only there was an association of increased WMH volume with expected years from symptom onset. The appearance of the WMH was also different in the GRN group compared with the other groups, with the lesions in the GRN group being more similar to each other. The presence of WMH in those with progranulin deficiency may be related to the known role of progranulin in neuroinflammation, although other roles are also proposed including an effect on blood-brain barrier permeability and the cerebral vasculature. Future studies will be useful to investigate the longitudinal evolution of WMH and their potential use as a biomarker as well as post-mortem studies investigating the histopathological nature of the lesions.
SN  - 2213-1582
UR  - http://dx.doi.org/10.1016/j.nicl.2017.04.015
N1  - This article is under Creative Commons licence Attribution 4.0 International (CC BY 4.0)
TI  - White matter hyperintensities are seen only in GRN mutation carriers in the GENFI cohort
EP  - 180
VL  - 15
AV  - public
Y1  - 2017///
SP  - 171
ER  -