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Cortical thickness in presymptomatic GRN and C9ORF72 mutation carriers Dowds, Emma Frances
Abstract
Objective: This thesis aimed to investigate cortical thickness in presymptomatic GRN and C9ORF72 mutation carriers prior to the onset of frontotemporal dementia (FTD). Methods: Subjects were recruited from 16 families with a family history of FTD caused by GRN or C9ORF72 mutations. The C9ORF72 group consisted of 8 mutation carriers (age 50.25 ± 6.90 years), 11 non-carrier family member controls (age 52.82 ± 17.15 years), and 3 affected carriers (age 55.00 ± 1.00 years). The GRN group consisted of 6 mutation carriers (age 53.33 ± 9.67 years) and 9 non-carrier family member controls (age 52.11 ± 8.82). Between group differences in cortical thickness were assessed using a surface based vertex-by-vertex model correcting for age, sex, MMSE and years to mean age of family onset. Significant clusters are reported at 10mm, 15mm and 20mm of smoothing and those identified at all three, two consecutive or one smoothing level are reported with strong, moderate and weak confidence, respectively. Results: Compared to non-carrier control family members, the C9ORF72 mutation carriers exhibited no difference in cognitive domain scores, but presented with strong to moderate asymmetrical patterns of thinning in the right temporoinsular and left mediofrontal and temporal regions. Compared to non-carrier controls, the GRN mutation carriers exhibited decreased performance on domains of working memory (p = 0.02) and executive function (p = 0.01), with a trend towards reduced language (p = 0.06) and visuospatial (p = 0.08) domains, but did not exhibit any difference in cortical thickness when compared to the non-carrier control family members. Conclusions: With the use of genetic screening and neuroimaging analyses this thesis demonstrated that grey matter atrophy occurs prior to cognitive decline in C9ORF72 mutation carriers, while GRN carriers exhibit subtle changes in cognitive domains prior to cortical grey matter atrophy. These findings could prove to be highly valuable as they suggest that the mechanism of disease progression between the two mutations may differ. As such, each mutation may require specific neuroimaging methods to track morphological changes prior to cognitive decline and clinical onset.
Item Metadata
Title |
Cortical thickness in presymptomatic GRN and C9ORF72 mutation carriers
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Creator | |
Publisher |
University of British Columbia
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Date Issued |
2014
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Description |
Objective: This thesis aimed to investigate cortical thickness in presymptomatic GRN
and C9ORF72 mutation carriers prior to the onset of frontotemporal dementia (FTD).
Methods: Subjects were recruited from 16 families with a family history of FTD caused
by GRN or C9ORF72 mutations. The C9ORF72 group consisted of 8 mutation carriers
(age 50.25 ± 6.90 years), 11 non-carrier family member controls (age 52.82 ± 17.15
years), and 3 affected carriers (age 55.00 ± 1.00 years). The GRN group consisted of 6
mutation carriers (age 53.33 ± 9.67 years) and 9 non-carrier family member controls
(age 52.11 ± 8.82). Between group differences in cortical thickness were assessed
using a surface based vertex-by-vertex model correcting for age, sex, MMSE and years
to mean age of family onset. Significant clusters are reported at 10mm, 15mm and
20mm of smoothing and those identified at all three, two consecutive or one smoothing
level are reported with strong, moderate and weak confidence, respectively.
Results: Compared to non-carrier control family members, the C9ORF72 mutation
carriers exhibited no difference in cognitive domain scores, but presented with strong to
moderate asymmetrical patterns of thinning in the right temporoinsular and left
mediofrontal and temporal regions. Compared to non-carrier controls, the GRN mutation
carriers exhibited decreased performance on domains of working memory (p = 0.02)
and executive function (p = 0.01), with a trend towards reduced language (p = 0.06) and
visuospatial (p = 0.08) domains, but did not exhibit any difference in cortical thickness
when compared to the non-carrier control family members.
Conclusions: With the use of genetic screening and neuroimaging analyses this thesis
demonstrated that grey matter atrophy occurs prior to cognitive decline in C9ORF72
mutation carriers, while GRN carriers exhibit subtle changes in cognitive domains prior
to cortical grey matter atrophy. These findings could prove to be highly valuable as they
suggest that the mechanism of disease progression between the two mutations may
differ. As such, each mutation may require specific neuroimaging methods to track
morphological changes prior to cognitive decline and clinical onset.
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Genre | |
Type | |
Language |
eng
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Date Available |
2014-07-04
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Provider |
Vancouver : University of British Columbia Library
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Rights |
Attribution-NonCommercial-NoDerivs 2.5 Canada
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DOI |
10.14288/1.0167513
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
2014-09
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Campus | |
Scholarly Level |
Graduate
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Rights URI | |
Aggregated Source Repository |
DSpace
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Rights
Attribution-NonCommercial-NoDerivs 2.5 Canada