J Patrick O'Grady1, Douglas C Dean2, Kao Lee Yang1, Cristybelle-Marie Canda1, Siobhan M Hoscheidt3, Erika J Starks1, Andrew Merluzzi1, Samuel Hurley4,5, Nancy J Davenport1,6, Ozioma C Okonkwo1,6, Rozalyn M Anderson7, Sanjay Asthana1,6,7, Sterling C Johnson1,6,7, Andrew L Alexander2, Barbara B Bendlin1,6. 1. Wisconsin Alzheimer's Disease Research Center, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, USA. 2. Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA. 3. Stitch Center for Healthy Aging and Alzheimer's Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA. 4. Department of Neuroscience, University of Wisconsin-Madison, Madison, Wisconsin, USA. 5. Department of Radiology, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, USA. 6. Wisconsin Alzheimer's Institute, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, USA. 7. Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin, USA.
Abstract
OBJECTIVE: Insulin regulates metabolism and influences neural health. Insulin resistance (IR) and type II diabetes have been identified as risk factors for Alzheimer disease (AD). Evidence has also suggested that myelinated white matter alterations may be involved in the pathophysiology of AD; however, it is unknown whether insulin or IR affect the underlying myelin microstructure. The relationships between insulin, IR, and myelin were examined, with the hypothesis that IR would be associated with reduced myelin. METHODS: Cognitively unimpaired adults enriched for risk factors for AD underwent multicomponent driven equilibrium single pulse observation of T1 and T2 imaging, a myelin-sensitive neuroimaging technique. Linear regressions were used to test the relationship between homeostatic model assessment of IR, insulin, and myelin water fraction (MWF) as well as interactions with APOE ε4. RESULTS: Both IR and insulin level were associated with altered myelin content, wherein a significant negative association with MWF was observed in white matter regions and a positive association with MWF was observed in gray matter. CONCLUSIONS: The results suggest that insulin and IR influence white matter myelination in a cognitively unimpaired population. Additional studies are needed to determine the extent to which this may contribute to cognitive decline or vulnerability to neurodegenerative disease.
OBJECTIVE:Insulin regulates metabolism and influences neural health. Insulin resistance (IR) and type II diabetes have been identified as risk factors for Alzheimer disease (AD). Evidence has also suggested that myelinated white matter alterations may be involved in the pathophysiology of AD; however, it is unknown whether insulin or IR affect the underlying myelin microstructure. The relationships between insulin, IR, and myelin were examined, with the hypothesis that IR would be associated with reduced myelin. METHODS: Cognitively unimpaired adults enriched for risk factors for AD underwent multicomponent driven equilibrium single pulse observation of T1 and T2 imaging, a myelin-sensitive neuroimaging technique. Linear regressions were used to test the relationship between homeostatic model assessment of IR, insulin, and myelin water fraction (MWF) as well as interactions with APOE ε4. RESULTS: Both IR and insulin level were associated with altered myelin content, wherein a significant negative association with MWF was observed in white matter regions and a positive association with MWF was observed in gray matter. CONCLUSIONS: The results suggest that insulin and IR influence white matter myelination in a cognitively unimpaired population. Additional studies are needed to determine the extent to which this may contribute to cognitive decline or vulnerability to neurodegenerative disease.