Age-related differences in white matter microstructure measured by advanced diffusion MRI in healthy older adults at risk for Alzheimer’s disease
Alice Motovylyak,
Nicholas M. Vogt,
Nagesh Adluru,
Yue Ma,
Rui Wang,
Jennifer M. Oh,
Steven R. Kecskemeti,
Andrew L. Alexander,
Douglas C. Dean,
Catherine L. Gallagher,
Mark A. Sager,
Bruce P. Hermann,
Howard A. Rowley,
Sterling C. Johnson,
Sanjay Asthana,
Barbara B. Bendlin,
Ozioma C. Okonkwo
Affiliations
Alice Motovylyak
Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI 53792, USA; Corresponding authors at: J5/M192 Clinical Science Center, 600 Highland Avenue, Madison, WI 53792, USA (A. Motovylyak). J5/M156, Clinical Science Center, 600 Highland Avenue, Madison, WI 53792, USA (O.C. Okonkwo).
Nicholas M. Vogt
Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI 53792, USA
Nagesh Adluru
Waisman Laboratory for Brain Imaging and Behavior, Waisman Center, University of Wisconsin, 1500 Highland Ave, Madison, WI 53705, USA; Department of Radiology, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI 53792, USA
Yue Ma
Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI 53792, USA
Rui Wang
Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI 53792, USA; The Swedish School of Sport and Health Science, GIH, Lidingövägen 1, Box 5626, SE-11486 Stockholm, Sweden
Jennifer M. Oh
Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI 53792, USA
Steven R. Kecskemeti
Waisman Laboratory for Brain Imaging and Behavior, Waisman Center, University of Wisconsin, 1500 Highland Ave, Madison, WI 53705, USA
Andrew L. Alexander
Waisman Laboratory for Brain Imaging and Behavior, Waisman Center, University of Wisconsin, 1500 Highland Ave, Madison, WI 53705, USA; Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, 1111 Highland Ave, Madison, WI 53705, USA; Department of Psychiatry, University of Wisconsin School of Medicine and Public Health, 6001 Research Park Blvd, Madison, WI 53705, USA
Douglas C. Dean
Waisman Laboratory for Brain Imaging and Behavior, Waisman Center, University of Wisconsin, 1500 Highland Ave, Madison, WI 53705, USA; Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, 1111 Highland Ave, Madison, WI 53705, USA; Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, 1111 Highland Ave, Madison, WI 53705, USA
Catherine L. Gallagher
Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI 53792, USA; Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veterans Hospital, 2500 Overlook Terrace, Madison, WI 53705, USA; Department of Neurology, University of Wisconsin School of Medicine and Public Health, 1111 Highland Ave, Madison, WI 53705, USA
Mark A. Sager
Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI 53792, USA; Wisconsin Alzheimer’s Institute, University of Wisconsin School of Medicine and Public Health, 610 Walnut St Suite 957, Madison, WI 53726, USA
Bruce P. Hermann
Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI 53792, USA; Wisconsin Alzheimer’s Institute, University of Wisconsin School of Medicine and Public Health, 610 Walnut St Suite 957, Madison, WI 53726, USA
Howard A. Rowley
Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI 53792, USA
Sterling C. Johnson
Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI 53792, USA; Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veterans Hospital, 2500 Overlook Terrace, Madison, WI 53705, USA
Sanjay Asthana
Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI 53792, USA; Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veterans Hospital, 2500 Overlook Terrace, Madison, WI 53705, USA
Barbara B. Bendlin
Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI 53792, USA
Ozioma C. Okonkwo
Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI 53792, USA; Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veterans Hospital, 2500 Overlook Terrace, Madison, WI 53705, USA; Corresponding authors at: J5/M192 Clinical Science Center, 600 Highland Avenue, Madison, WI 53792, USA (A. Motovylyak). J5/M156, Clinical Science Center, 600 Highland Avenue, Madison, WI 53792, USA (O.C. Okonkwo).
Neurite orientation dispersion and density imaging (NODDI) is an advanced diffusion imaging technique, which can detect more distinct microstructural features compared to conventional Diffusion Tensor Imaging (DTI). NODDI allows the signal to be divided into multiple water compartments and derive measures for orientation dispersion index (ODI), neurite density index (NDI) and volume fraction of isotropic diffusion compartment (FISO). This study aimed to investigate which diffusion metric—fractional anisotropy (FA), mean diffusivity (MD), NDI, ODI, or FISO—is most influenced by aging and reflects cognitive function in a population of healthy older adults at risk for Alzheimer’s disease (AD). Age was significantly associated with all but one diffusion parameters and regions of interest. NDI and MD in the cingulate region adjacent to the cingulate cortex showed a significant association with a composite measure of Executive Function and was proven to partially mediate the relationship between aging and Executive Function decline. These results suggest that both DTI and NODDI parameters are sensitive to age-related differences in white matter regions vulnerable to aging, particularly among older adults at risk for AD.
