TY - JOUR
T1 - Reduced fractional anisotropy of the genu of the corpus callosum as a cerebrovascular disease marker and predictor of longitudinal cognition in MCI
AU - Raghavan, Sheelakumari
AU - Przybelski, Scott A.
AU - Reid, Robert I.
AU - Graff-Radford, Jonathan
AU - Lesnick, Timothy G.
AU - Zuk, Samantha M.
AU - Knopman, David S.
AU - Machulda, Mary M.
AU - Mielke, Michelle M.
AU - Petersen, Ronald C.
AU - Jack, Clifford R.
AU - Vemuri, Prashanthi
N1 - Funding Information:
The authors report no conflicts of interest relevant to this manuscript. Dr. Knopman reported serving on a data safety monitoring board for the DIAN study, serving on a Data Safety monitoring Board for a tau therapeutic for Biogen, but receives no personal compensation, and serving as an investigator in a clinical trials sponsored by Lilly Pharmaceuticals and the University of Southern California, and receiving research support from the National Institutes of Health (NIH) outside the submitted work. Dr. Graff-Radford reported receiving research support from the National Institute on Aging outside the submitted work. Dr. Mielke reported receiving research support from the NIH, Department of Defense, and unrestricted research grants from Biogen outside the submitted work. Dr. Jack reported consulting for Eli Lilly, serving on an independent data monitoring board for Roche, and serving as a speaker for Eisai but receives no personal compensation from any commercial entity; he also reported receiving research support from the NIH and the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Clinic. Dr. Petersen reported receiving consulting fees from Hoffman-La Roche Inc, Merck Inc, Genentech Inc, Biogen Inc, GE Healthcare, and Eisai Inc. outside the submitted work. Dr. Vemuri reported receiving grants from the NIH during the conduct of the study.
Funding Information:
This work was supported by NIH grants R01 NS097495 (PI: Vemuri), R01 AG056366 (PI: Vemuri), U01 AG006786 (PI: Petersen), P50 AG016574 (PI: Petersen), R37 AG011378 (PI: Jack), R01 AG041851 (PIs: Jack and Knopman); R01 AG034676 (Rochester Epidemiology Project PI: Rocca); the Gerald and Henrietta Rauenhorst Foundation grant, the Millis Family, the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Foundation, Alzheimer's Association (Zenith Fellows Award), Liston Award, Elsie and Marvin Dekelboum Family Foundation, Schuler Foundation, and Opus building NIH grant C06 RR018898. The data contained in the manuscript being submitted have not been previously published, have not been submitted elsewhere, and will not be submitted elsewhere while under consideration at Neurobiology of Aging. The study was approved by the Mayo Clinic and Olmsted Medical Center institutional review board, and written informed consent was obtained from all participants. All authors have reviewed the contents of the manuscript being submitted, approved of its contents, and validated the accuracy of the data.The authors thank all the study participants and staff in the Mayo Clinic Study of Aging, Mayo Alzheimer's Disease Research Center, and Aging Dementia Imaging Research laboratory at the Mayo Clinic for making this study possible. The authors gratefully acknowledge the support of NVIDIA Corporation for the donation of the Quadro P5000 GPU used in this research.
Funding Information:
This work was supported by NIH grants R01 NS097495 (PI: Vemuri), R01 AG056366 (PI: Vemuri), U01 AG006786 (PI: Petersen), P50 AG016574 (PI: Petersen), R37 AG011378 (PI: Jack), R01 AG041851 (PIs: Jack and Knopman); R01 AG034676 (Rochester Epidemiology Project PI: Rocca); the Gerald and Henrietta Rauenhorst Foundation grant, the Millis Family, the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Foundation, Alzheimer's Association (Zenith Fellows Award), Liston Award, Elsie and Marvin Dekelboum Family Foundation, Schuler Foundation, and Opus building NIH grant C06 RR018898. The data contained in the manuscript being submitted have not been previously published, have not been submitted elsewhere, and will not be submitted elsewhere while under consideration at Neurobiology of Aging. The study was approved by the Mayo Clinic and Olmsted Medical Center institutional review board, and written informed consent was obtained from all participants. All authors have reviewed the contents of the manuscript being submitted, approved of its contents, and validated the accuracy of the data.The authors thank all the study participants and staff in the Mayo Clinic Study of Aging , Mayo Alzheimer's Disease Research Center , and Aging Dementia Imaging Research laboratory at the Mayo Clinic for making this study possible. The authors gratefully acknowledge the support of NVIDIA Corporation for the donation of the Quadro P5000 GPU used in this research.
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/12
Y1 - 2020/12
N2 - Our goal was to evaluate the utility of diffusion tensor imaging (DTI) for predicting future cognitive decline in mild cognitive impairment (MCI) in conjunction with Alzheimer's disease (AD) biomarkers (amyloid positron emission tomography and AD signature neurodegeneration) in 132 MCI individuals ≥60 year old with structural magnetic resonance imaging, DTI, amyloid positron emission tomography, and at least one clinical follow-up. We used mixed-effect models to evaluate the prognostic ability of fractional anisotropy of the genu of the corpus callosum (FA-Genu), as a cerebrovascular disease marker, for predicting cognitive decline along with AD biomarkers. We contrasted the value of white matter hyperintensities, a traditional cerebrovascular disease marker as well as FA in the hippocampal cingulum bundle with the FA-Genu models. FA-Genu significantly predicted cognitive decline even after accounting for AD biomarkers. WMH was not associated with cognitive decline in the model with both WMH and FA-Genu. DTI specifically FA-Genu provides unique complementary information to AD biomarkers and has significant utility for prediction of cognitive decline in MCI.
AB - Our goal was to evaluate the utility of diffusion tensor imaging (DTI) for predicting future cognitive decline in mild cognitive impairment (MCI) in conjunction with Alzheimer's disease (AD) biomarkers (amyloid positron emission tomography and AD signature neurodegeneration) in 132 MCI individuals ≥60 year old with structural magnetic resonance imaging, DTI, amyloid positron emission tomography, and at least one clinical follow-up. We used mixed-effect models to evaluate the prognostic ability of fractional anisotropy of the genu of the corpus callosum (FA-Genu), as a cerebrovascular disease marker, for predicting cognitive decline along with AD biomarkers. We contrasted the value of white matter hyperintensities, a traditional cerebrovascular disease marker as well as FA in the hippocampal cingulum bundle with the FA-Genu models. FA-Genu significantly predicted cognitive decline even after accounting for AD biomarkers. WMH was not associated with cognitive decline in the model with both WMH and FA-Genu. DTI specifically FA-Genu provides unique complementary information to AD biomarkers and has significant utility for prediction of cognitive decline in MCI.
KW - Cerebrovascular disease
KW - Diffusion tensor imaging
KW - Genu of the corpus callosum
KW - Mild cognitive impairment
UR - http://www.scopus.com/inward/record.url?scp=85091934023&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85091934023&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2020.09.005
DO - 10.1016/j.neurobiolaging.2020.09.005
M3 - Article
C2 - 33022474
AN - SCOPUS:85091934023
SN - 0197-4580
VL - 96
SP - 176
EP - 183
JO - Neurobiology of aging
JF - Neurobiology of aging
ER -