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Abstract
Objective: To describe the phenotype of patients with C9FTD/ALS (C9ORF72) hexanucleotide repeat expansion.
Methods: A total of 648 patients with frontotemporal dementia (FTD)–related clinical diagnoses and Alzheimer disease (AD) dementia were tested for C9ORF72 expansion and 31 carried expanded repeats (C9+). Clinical and neuroimaging data were compared between C9+ (15 behavioral variant FTD [bvFTD], 11 FTD–motor neuron disease [MND], 5 amyotrophic lateral sclerosis [ALS]) and sporadic noncarriers (48 bvFTD, 19 FTD-MND, 6 ALS).
Results: All C9+ patients displayed clinical syndromes of bvFTD, ALS, or FTD-MND. At first evaluation, C9+ bvFTD patients had more delusions and greater impairment of working memory, but milder eating dysregulation compared to bvFTD noncarriers. C9+FTD-MND patients had a trend for longer survival and had an earlier age at onset than FTD-MND noncarriers. Voxel-based morphometry demonstrated more thalamic atrophy in FTD and FTD-MND carriers than in noncarriers.
Conclusions: Patients with the C9ORF72 hexanucleotide repeat expansion develop bvFTD, ALS, or FTD-MND with similar clinical and imaging features to sporadic cases. Other FTD spectrum diagnoses and AD dementia appear rare or absent among C9+ individuals. Longer survival in C9+ FTD-MND suggests slower disease progression and thalamic atrophy represents a novel and unexpected feature.
GLOSSARY
- AD=
- Alzheimer disease;
- ALS=
- amyotrophic lateral sclerosis;
- bvFTD=
- behavioral variant frontotemporal dementia;
- CBS=
- corticobasal syndrome;
- CDR-SB=
- Clinical Dementia Rating Scale sum of boxes;
- FTD=
- frontotemporal dementia;
- FWE=
- familywise error;
- glm=
- generalized linear model;
- lvPPA=
- logopenic variant primary progressive aphasia;
- MND=
- motor neuron disease;
- nfvPPA=
- nonfluent variant primary progressive aphasia;
- NPI=
- Neuropsychiatric Inventory;
- PSP=
- progressive supranuclear palsy;
- svPPA=
- semantic variant primary progressive aphasia;
- UCSF=
- University of California, San Francisco;
- VBM=
- voxel-based morphometry
Footnotes
-
Editorial, page 962
-
See page 995
-
Supplemental data at www.neurology.org
- Received January 9, 2012.
- Accepted March 8, 2012.
- Copyright © 2012 by AAN Enterprises, Inc.
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