@article{5278d877e5714f3481a6f19f026fd12c,
title = "MRI quantitative susceptibility mapping of the substantia nigra as an early biomarker for Lewy body disease",
abstract = "Background and Purpose: Neurodegeneration of the substantia nigra in Lewy body disease is associated with iron deposition, which increases the magnetic susceptibility of the substantia nigra on MRI. Our objective was to measure iron deposition in the substantia nigra in patients with probable dementia with Lewy bodies (pDLB) and patients who are at risk for pDLB by quantitative susceptibility mapping (QSM). Methods: Participants included pDLB (n = 36), mild cognitive impairment with at least one core feature of DLB (MCI-LB; n = 15), idiopathic rapid eye movement sleep behavior disorder (iRBD; n = 11), and an age-and gender-matched clinically unimpaired control group (n = 102). QSM was derived from multi-echo 3D gradient recalled echo MRI at 3T, and groups were compared on mean susceptibility values of the substantia nigra and its relation to parkinsonism severity. Results: Patients with pDLB had higher susceptibility in the substantia nigra compared to controls (p< 0.001) and MCI-LB (p = 0.043). The susceptibility of substantia nigra showed an increasing trend from controls to iRBD and MCI-LB, and to pDLB (p< 0.001). Parkinsonism severity was not associated with the mean susceptibility in the substantia nigra in the patient groups. Conclusions: Our data suggested that QSM is sensitive to the increased magnetic susceptibility due to higher iron content in the substantia nigra in pDLB. The trend of increasing susceptibility from controls to iRBD and MCI-LB, and to pDLB suggests that iron deposition in the substantia nigra starts to increase as early as the prodromal stage in DLB and continues to increase as the disease progresses, independent of parkinsonism severity.",
keywords = "dementia with Lewy bodies, iron, mild cognitive impairment, quantitative susceptibility mapping",
author = "Qin Chen and Boeve, {Bradley F.} and Arvin Forghanian-Arani and Senjem, {Matthew L.} and Jack, {Clifford R.} and Przybelski, {Scott A.} and Lesnick, {Timothy G.} and Kremers, {Walter K.} and Fields, {Julie A.} and Schwarz, {Christopher G.} and Gunter, {Jeffrey L.} and Trzasko, {Joshua D.} and Jonathan Graff-Radford and Rodolfo Savica and Knopman, {David S.} and Dickson, {Dennis W.} and Ferman, {Tanis J.} and Neill Graff-Radford and Petersen, {Ronald C.} and Kejal Kantarci",
note = "Funding Information: This study was funded by the NIH (U01 NS100620, R01 AG040042, R01 AG11378, P50 AG16574, U01 AG06786, P30 AG062677, and C06 RR018898), the Foundation Dr. Corinne Schulerand, the Mangurian Foundation for Lewy Body Research, the Elsie and Marvin Dekelboum Family Foundation, and the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program. We are grateful to our patients and caregivers for their participation in our detailed annual assessments and for their involvement in current study. Dr. Boeve has served as an investigator for clinical trials sponsored by Biogen, Alector, and EIP Pharma. He receives royalties from the publication of a book entitled Behavioral Neurology of Dementia (Cambridge Medicine, 2009, 2017). He serves on the Scientific Advisory Board of the Tau Consortium. He receives research support from the NIH, the Mayo Clinic Dorothy and Harry T. Mangurian Jr. Lewy Body Dementia Program, the Little Family Foundation, and the Turner Family Foundation. Dr. Jack consults for Eli Lilly and serves on an independent data monitoring board for Roche but he receives no personal compensation from any commercial entity. He receives research support from the NIH. KW Kremers receives research funding from AstraZeneca, Biogen, Roche, DOD, and NIH. Dr. Fields receives research support from NIH. Dr. J. Graff-Radford receives research support from the NIH. Dr. Knopman serves on the DSMB of the DIAN-TU study, is a site PI for clinical trials sponsored by Biogen, Lilly and the University of Southern California, and is funded by NIH. Dr. Dickson is an editorial board member for Acta Neuropathologica, Brain, Brain Pathology, Neuropathology and Applied Neurobiology, Annals of Neurology, Neuropathology and editor for the International Journal of Clinical and Experimental Pathology and American Journal of Neurodegenerative Disease. He is supported by the Mangurian Foundation for Lewy body disease research and NIH. Dr. Ferman receives funding from the Mangurian Foundation for Lewy body research and NIH. Dr. N. Graff-Radford receives royalties from UpToDate, has participated in multicenter therapy studies by sponsored by Biogen, TauRx, AbbVie, Novartis, and Lilly. He receives receives research support from NIH. Dr. Petersen serves on scientific advisory boards for Elan Pharmaceuticals, Wyeth Pharmaceuticals, and GE Healthcare; receives royalties from publishing Mild Cognitive Impairment (Oxford University Press, 2003). He also receives research support from NIH. Dr. Kantarci serves on the Data Safety Monitoring Board for Takeda Global Research & Development Center, Inc. She consults Biogen Inc. She receives research support from the Avid Radiopharmaceuticals, Eli Lilly. She is funded by the Alzheimer's Drug Discovery Foundation and NIH. The other authors have nothing to disclose. Funding Information: This study was funded by the NIH (U01 NS100620, R01 AG040042, R01 AG11378, P50 AG16574, U01 AG06786, P30 AG062677, and C06 RR018898), the Foundation Dr. Corinne Schulerand, the Mangurian Foundation for Lewy Body Research, the Elsie and Marvin Dekelboum Family Foundation, and the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program. We are grateful to our patients and caregivers for their participation in our detailed annual assessments and for their involvement in current study. Dr. Boeve has served as an investigator for clinical trials sponsored by Biogen, Alector, and EIP Pharma. He receives royalties from the publication of a book entitled Behavioral Neurology of Dementia (Cambridge Medicine, 2009, 2017). He serves on the Scientific Advisory Board of the Tau Consortium. He receives research support from the NIH, the Mayo Clinic Dorothy and Harry T. Mangurian Jr. Lewy Body Dementia Program, the Little Family Foundation, and the Turner Family Foundation. Dr. Jack consults for Eli Lilly and serves on an independent data monitoring board for Roche but he receives no personal compensation from any commercial entity. He receives research support from the NIH. KW Kremers receives research funding from AstraZeneca, Biogen, Roche, DOD, and NIH. Dr. Fields receives research support from NIH. Dr. J. Graff‐Radford receives research support from the NIH. Dr. Knopman serves on the DSMB of the DIAN‐TU study, is a site PI for clinical trials sponsored by Biogen, Lilly and the University of Southern California, and is funded by NIH. Dr. Dickson is an editorial board member for Acta Neuropathologica, Brain, Brain Pathology, Neuropathology and Applied Neurobiology, Annals of Neurology, Neuropathology and editor for the International Journal of Clinical and Experimental Pathology and American Journal of Neurodegenerative Disease. He is supported by the Mangurian Foundation for Lewy body disease research and NIH. Dr. Ferman receives funding from the Mangurian Foundation for Lewy body research and NIH. Dr. N. Graff‐Radford receives royalties from UpToDate, has participated in multicenter therapy studies by sponsored by Biogen, TauRx, AbbVie, Novartis, and Lilly. He receives receives research support from NIH. Dr. Petersen serves on scientific advisory boards for Elan Pharmaceuticals, Wyeth Pharmaceuticals, and GE Healthcare; receives royalties from publishing Mild Cognitive Impairment (Oxford University Press, 2003). He also receives research support from NIH. Dr. Kantarci serves on the Data Safety Monitoring Board for Takeda Global Research & Development Center, Inc.. She consults Biogen Inc. She receives research support from the Avid Radiopharmaceuticals, Eli Lilly. She is funded by the Alzheimer's Drug Discovery Foundation and NIH. The other authors have nothing to disclose. Publisher Copyright: {\textcopyright} 2021 American Society of Neuroimaging",
year = "2021",
month = sep,
day = "1",
doi = "10.1111/jon.12878",
language = "English (US)",
volume = "31",
pages = "1020--1027",
journal = "Journal of Neuroimaging",
issn = "1051-2284",
publisher = "Wiley-Blackwell",
number = "5",
}