Auriel A Willette1, Sterling C Johnson2, Alex C Birdsill3, Mark A Sager4, Bradley Christian5, Laura D Baker6, Suzanne Craft6, Jennifer Oh3, Eric Statz3, Bruce P Hermann4, Erin M Jonaitis7, Rebecca L Koscik7, Asenath La Rue7, Sanjay Asthana3, Barbara B Bendlin8. 1. Geriatric Research Education and Clinical Center, Wm. S. Middleton Memorial Veterans Hospital, Madison, WI, USA; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Laboratory of Neurosciences, National Institute on Aging, Baltimore, MD, USA. 2. Geriatric Research Education and Clinical Center, Wm. S. Middleton Memorial Veterans Hospital, Madison, WI, USA; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin-Madison, Madison, WI, USA; Wisconsin Alzheimer's Institute, Wisconsin School of Medicine and Public Health, Madison, WI, USA. 3. Geriatric Research Education and Clinical Center, Wm. S. Middleton Memorial Veterans Hospital, Madison, WI, USA; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. 4. Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Wisconsin Alzheimer's Institute, Wisconsin School of Medicine and Public Health, Madison, WI, USA. 5. Department of Medical Physics, Wisconsin School of Medicine and Public Health, Madison, WI, USA. 6. Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA. 7. Wisconsin Alzheimer's Institute, Wisconsin School of Medicine and Public Health, Madison, WI, USA. 8. Geriatric Research Education and Clinical Center, Wm. S. Middleton Memorial Veterans Hospital, Madison, WI, USA; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. Electronic address: bbb@medicine.wisc.edu.
Abstract
BACKGROUND: Insulin resistance (IR) increases Alzheimer's disease (AD) risk. IR is related to greater amyloid burden post-mortem and increased deposition within areas affected by early AD. No studies have examined if IR is associated with an in vivo index of amyloid in the human brain in late middle-aged participants at risk for AD. METHODS: Asymptomatic, late middle-aged adults (N = 186) from the Wisconsin Registry for Alzheimer's Prevention underwent [C-11]Pittsburgh compound B (PiB) positron emission tomography. The cross-sectional design tested the interaction between insulin resistance and glycemic status on PiB distribution volume ratio in three regions of interest (frontal, parietal, and temporal). RESULTS: In participants with normoglycemia but not hyperglycemia, higher insulin resistance corresponded to higher PiB uptake in frontal and temporal areas, reflecting increased amyloid deposition. CONCLUSIONS: This is the first human study to demonstrate that insulin resistance may contribute to amyloid deposition in brain regions affected by AD.
BACKGROUND:Insulin resistance (IR) increases Alzheimer's disease (AD) risk. IR is related to greater amyloid burden post-mortem and increased deposition within areas affected by early AD. No studies have examined if IR is associated with an in vivo index of amyloid in the human brain in late middle-aged participants at risk for AD. METHODS: Asymptomatic, late middle-aged adults (N = 186) from the Wisconsin Registry for Alzheimer's Prevention underwent [C-11]Pittsburgh compound B (PiB) positron emission tomography. The cross-sectional design tested the interaction between insulin resistance and glycemic status on PiB distribution volume ratio in three regions of interest (frontal, parietal, and temporal). RESULTS: In participants with normoglycemia but not hyperglycemia, higher insulin resistance corresponded to higher PiB uptake in frontal and temporal areas, reflecting increased amyloid deposition. CONCLUSIONS: This is the first human study to demonstrate that insulin resistance may contribute to amyloid deposition in brain regions affected by AD.
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