TY - JOUR
T1 - Frontotemporal dementia due To C9ORF72 mutations clinical and imaging features
AU - Sha, Sharon J.
AU - Takada, Leonel T.
AU - Rankin, Katherine P.
AU - Yokoyama, Jennifer S.
AU - Rutherford, Nicola J.
AU - Fong, Jamie C.
AU - Khan, Baber
AU - Karydas, Anna
AU - Baker, Matt C.
AU - De Jesus-Hernandez, Mariely
AU - Pribadi, Mochtar
AU - Coppola, Giovanni
AU - Geschwind, Daniel H.
AU - Rademakers, Rosa
AU - Lee, Suzee E.
AU - Seeley, William
AU - Miller, Bruce L.
AU - Boxer, Adam L.
N1 - Funding Information:
Dr. Sha and Dr. Takada report no disclosures. Dr. Rankin is funded by NIH/NIA 1R01AG029577–01 and Hillblom 2007/2I . Dr. Yokoyama, N.J. Rutherford, J.C. Fong, B. Khan, A. Karydas, and M.C. Baker report no disclosures. M. DeJesus-Hernandez has a patent pending on Expanded non-coding repeat in C9ORF72 cause frontotemporal dementia and amyotrophic lateral sclerosis. Dr. Pribadi reports no disclosures. Dr. Coppola is funded by NIH/NIA grant : RC1 AG035610 . Dr. Geschwind has received institutional support from Alzheimer's Disease Research Center of California (ARCC) grant 03–7527 and is funded by NIH grant R01 AG026938 . Dr. Rademakers is funded by NIH grants R01NS065782, R01AG026251 , ALS Association, and has a patent pending on Expanded non-coding repeat in C9ORF72 cause frontotemporal dementia and amyotrophic lateral sclerosis. Dr. Lee is funded by K23AG039414–01A1 and the Tau Consortium. Dr. Seeley is funded by NIH grants P50 AG1657303 , the John Douglas French Alzheimer's Disease Foundation, Consortium for Frontotemporal Dementia Research, James S. McDonnell Foundation, Larry Hillblom Foundation, has received support for travel by the Alzheimer's Association, and received payment for lectures by the Alzheimer's Association, American Academy of Neurology, and Novartis Korea. Dr. Miller serves as board member on the John Douglas French Alzheimer's Foundation and Larry L. Hillblom Foundation, serves as a consultant for TauRx, Ltd., Allon Therapeutics, the Tau Consortium, and the Consortium for Frontotemporal research, has received institutional support from Novartis, and is funded by NIH grants P50AG023501, P01AG019724, P50 AG1657303 , and the state of CA. Dr. Boxer has been a consultant for Bristol Myers Squibb, Genentech, Plexikkon, Phloronol, Registrat-Mapi, Accera, Envivo, TauRx, and Novartis, receives research support from Allon Therapeutics, Bristol Myers Squibb, Janssen, Forest, Pfizer, Medivation, and Genentech, and is funded by NIH grants R01AG038791, R01AG031278 , the John Douglas French Foundation, Alzheimer's Drug Discovery Foundation, the Association for Frontotemporal Degeneration, the Silicon Valley Foundation, the Agouron Institute, the Tau Research Consortium, and the Hellman Family Foundation. Go to Neurology.org for full disclosures.
PY - 2012/9/4
Y1 - 2012/9/4
N2 - 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 behavoral 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 nove and unexpected feature.
AB - 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 behavoral 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 nove and unexpected feature.
UR - http://www.scopus.com/inward/record.url?scp=84866081962&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84866081962&partnerID=8YFLogxK
U2 - 10.1212/WNL.0b013e318268452e
DO - 10.1212/WNL.0b013e318268452e
M3 - Article
C2 - 22875087
AN - SCOPUS:84866081962
SN - 0028-3878
VL - 79
SP - 1002
EP - 1011
JO - Neurology
JF - Neurology
IS - 10
ER -