Brain atrophy over time in genetic and sporadic frontotemporal dementia: a study of 198 serial magnetic resonance images. (12th February 2015)

• Record Type: Journal Article
• 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.
• Is Part Of: European journal of neurology. Volume 22:Number 5(2015:May)
• Page Start: 745
• Page End: 752
• Publication Date: 2015-02-12
• Subjects: Neurology -- Periodicals; Nervous system -- Diseases -- Periodicals; 616.8
• DOI: 10.1111/ene.12675
• Languages: English
• ISSNs: 1351-5101

Abstract

<abstract abstract-type="main" id="ene12675-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ene12675-sec-0001" sec-type="section"> <title>Background and purpose</title> <p>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 (<italic>MAPT</italic>) and progranulin (<italic>GRN</italic>) mutations and <italic>C9ORF72</italic> repeat expansions, as well as sporadic FTD.</p> </sec> <sec id="ene12675-sec-0002" sec-type="section"> <title>Methods</title> <p>In this longitudinal study, 58 subjects were identified who had at least two MRI and <italic>MAPT</italic> mutations (<italic>n</italic> = 21), <italic>GRN</italic> mutations (<italic>n</italic> = 11), <italic>C9ORF72</italic> repeat expansions (<italic>n</italic> = 11) or sporadic FTD (<italic>n</italic> = 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.</p> </sec> <sec id="ene12675-sec-0003" sec-type="section"> <title>Results</title> <p>Progressive brain atrophy was observed in all groups, with fastest rates of whole brain atrophy in <italic>GRN</italic>, followed by sporadic FTD, <italic> C9ORF72</italic> and <italic>MAPT</italic>. All variants showed greatest rates in the frontal and temporal lobes, with parietal lobes also strikingly affected in <italic>GRN</italic>. Regional rates of atrophy across all lobes were greater in <italic>GRN</italic> compared to the other groups. <italic>C9ORF72</italic> showed greater rates of atrophy in the left cerebellum and right occipital lobe than <italic>MAPT</italic>, and sporadic FTD showed greater rates in the anterior cingulate than <italic>C9ORF72</italic> and <italic>MAPT</italic>. Sample size estimates were lowest using temporal lobe rates in <italic>GRN</italic>, ventricular rates in <italic>MAPT</italic> and <italic>C9ORF72</italic>, and whole brain rates in sporadic FTD.</p> </sec> <sec id="ene12675-sec-0004" sec-type="section"> <title>Conclusion</title> <p>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.</p> </sec> </abstract>