Dement Neurocogn Disord.  2015 Dec;14(4):163-167. 10.12779/dnd.2015.14.4.163.

A Voxel Based Morphometric Analysis of Longitudinal Cortical Gray Matter Changes in Progranulin Mutation Carriers At-Risk for Frontotemporal Dementia: Preliminary Study

• Youn YC
• Hsiung GY

• KMID: 2442934
• DOI: http://doi.org/10.12779/dnd.2015.14.4.163

Abstract

BACKGROUND AND PURPOSE
One of the most common genetic causes of frontotemporal dementia (FTD) is mutation in the progranulin (PGRN) gene. The aim of this study is to assess the early effects of the PGRN mutations on brain volumes by longitudinal voxel based morphometric (VBM) evaluation in asymptomatic mutation carriers.
METHODS
We recruited 17 asymptomatic members of families with FTD caused by PGRN mutations; 7 mutation carriers (51.0+/-11.6 yr) and 10 non-carriers (55.2+/-6.0 yr, p=0.404). The MRI follow-up intervals of carriers and non-carriers were 788.6+/-103.8 and 922.0+/-225.1 days (p=0.124) respectively. We performed cross-sectional and longitudinal VBM analysis on both groups.
RESULTS
At baseline, the carriers had lower white matter (WM) volumes in left frontal regions (p<0.001, uncorrected), but had no gray matter (GM) volume reduction. The carrier's global GM (p=0.924) and WM volume (p=0.364) reduction rate were not different from the non-carrier's. However, statistical parametric mapping T-maps showed differentially increased GM volume reductions in the bilateral parietal areas of carriers (p<0.001, uncorrected).
CONCLUSIONS
The findings from this study to examine WM and GM cross-sectional and longitudinal changes in PGRN mutation carriers suggest that WM atrophic changes could precede both GM changes and symptom onset in FTD. Asymptomatic PGRN mutation carriers have measurably higher rates of regional GM atrophy than non-carriers even in the pre-dementia stages.

Keyword

frontotemporal dementia; progranulin; voxel-based morphometry; gray matter volume reduction; cortical atrophy

MeSH Terms

Atrophy
Brain
Follow-Up Studies
Frontotemporal Dementia*
Humans
Magnetic Resonance Imaging
Rabeprazole

Figure

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  Fig. 1 Baseline of statistical parametric map of GM (A) and WM (B) regional volume reductions of frontotemporal dementia unaffected progranulin mutation carriers versus unaffected non-carrier. There is no significant GM atrophic area seen (controlled by age, uncorrected p<0.001) but WM reductions in left frontal area. GM: gray matter, SPM: statistical parametric mapping, WM: white matter.

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  Fig. 2 Statistical parametric map of longitudinal GM (A). Steeper GM changes were in bilateral middle parietal and right frontal areas (controlled by age and follow-up interval, uncorrected p<0.001). The changes of estimated marginal means of normalized GM volume of frontotemporal dementia unaffected PGRN carriers and non-carriers (B). GM: gray matter, PGRN: progranulin.

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