Elevated Insulin and Insulin Resistance are Associated with Altered Myelin in Cognitively Unimpaired Middle-Aged Adults

O'Grady JP, Dean DC 3rd, Yang KL, Canda CM, Hoscheidt SM, Starks EJ, Merluzzi A, Hurley S, Davenport NJ, Okonkwo OC, Anderson RM, Asthana S, Johnson SC, Alexander AL, Bendlin BB.

Obesity (Silver Spring). 2019 Jul 17. doi: 10.1002/oby.22558. [Epub ahead of print]


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.


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