Brain atrophy over time in genetic and sporadic frontotemporal dementia: a study of 198 serial magnetic resonance images.
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| Title: | Brain atrophy over time in genetic and sporadic frontotemporal dementia: a study of 198 serial magnetic resonance images. |
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| Authors: | Whitwell, J. L., Boeve, B. F., Weigand, S. D., Senjem, M. L., Gunter, J. L., Baker, M. C., DeJesus ‐ Hernandez, M., Knopman, D. S., Wszolek, Z. K., Petersen, R. C., Rademakers, R., Jack, C. R., Josephs, K. A. |
| Source: | European Journal of Neurology. May2015, Vol. 22 Issue 5, p745-752. 8p. |
| Subjects: | Cerebral atrophy, Magnetic resonance imaging, Brain imaging, Biomarkers, Longitudinal method, Genetic mutation, Temporal lobe |
| Abstract: | Background and purpose The aim of our study was to determine the utility of longitudinal magnetic resonance imaging ( MRI) measurements as potential biomarkers in the main genetic variants of frontotemporal dementia ( FTD), including microtubule-associated protein tau ( MAPT) and progranulin ( GRN) mutations and C9 ORF72 repeat expansions, as well as sporadic FTD. Methods In this longitudinal study, 58 subjects were identified who had at least two MRI and MAPT mutations ( n = 21), GRN mutations ( n = 11), C9 ORF72 repeat expansions ( n = 11) or sporadic FTD ( n = 15). A total of 198 serial MRI measurements were analyzed. Rates of whole brain atrophy were calculated using the boundary shift integral. Regional rates of atrophy were calculated using tensor-based morphometry. Sample size estimates were calculated. Results Progressive brain atrophy was observed in all groups, with fastest rates of whole brain atrophy in GRN, followed by sporadic FTD, C9 ORF72 and MAPT. All variants showed greatest rates in the frontal and temporal lobes, with parietal lobes also strikingly affected in GRN. Regional rates of atrophy across all lobes were greater in GRN compared to the other groups. C9 ORF72 showed greater rates of atrophy in the left cerebellum and right occipital lobe than MAPT, and sporadic FTD showed greater rates in the anterior cingulate than C9 ORF72 and MAPT. Sample size estimates were lowest using temporal lobe rates in GRN, ventricular rates in MAPT and C9 ORF72, and whole brain rates in sporadic FTD. Conclusion These data support the utility of using rates of atrophy as outcome measures in future drug trials in FTD and show that different imaging biomarkers may offer advantages in the different variants of FTD. [ABSTRACT FROM AUTHOR] |
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| Database: | Psychology and Behavioral Sciences Collection |
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| Abstract: | Background and purpose The aim of our study was to determine the utility of longitudinal magnetic resonance imaging ( MRI) measurements as potential biomarkers in the main genetic variants of frontotemporal dementia ( FTD), including microtubule-associated protein tau ( MAPT) and progranulin ( GRN) mutations and C9 ORF72 repeat expansions, as well as sporadic FTD. Methods In this longitudinal study, 58 subjects were identified who had at least two MRI and MAPT mutations ( n = 21), GRN mutations ( n = 11), C9 ORF72 repeat expansions ( n = 11) or sporadic FTD ( n = 15). A total of 198 serial MRI measurements were analyzed. Rates of whole brain atrophy were calculated using the boundary shift integral. Regional rates of atrophy were calculated using tensor-based morphometry. Sample size estimates were calculated. Results Progressive brain atrophy was observed in all groups, with fastest rates of whole brain atrophy in GRN, followed by sporadic FTD, C9 ORF72 and MAPT. All variants showed greatest rates in the frontal and temporal lobes, with parietal lobes also strikingly affected in GRN. Regional rates of atrophy across all lobes were greater in GRN compared to the other groups. C9 ORF72 showed greater rates of atrophy in the left cerebellum and right occipital lobe than MAPT, and sporadic FTD showed greater rates in the anterior cingulate than C9 ORF72 and MAPT. Sample size estimates were lowest using temporal lobe rates in GRN, ventricular rates in MAPT and C9 ORF72, and whole brain rates in sporadic FTD. Conclusion These data support the utility of using rates of atrophy as outcome measures in future drug trials in FTD and show that different imaging biomarkers may offer advantages in the different variants of FTD. [ABSTRACT FROM AUTHOR] |
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| ISSN: | 13515101 |
| DOI: | 10.1111/ene.12675 |
