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. 2013 Feb;36(2):443-9.
doi: 10.2337/dc12-0922. Epub 2012 Oct 15.

Insulin Resistance, Brain Atrophy, and Cognitive Performance in Late Middle-Aged Adults

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Free PMC article

Insulin Resistance, Brain Atrophy, and Cognitive Performance in Late Middle-Aged Adults

Auriel A Willette et al. Diabetes Care. .
Free PMC article

Abstract

Objective: Insulin resistance dysregulates glucose uptake and other functions in brain areas affected by Alzheimer disease. Insulin resistance may play a role in Alzheimer disease etiopathogenesis. This longitudinal study examined whether insulin resistance among late middle-aged, cognitively healthy individuals was associated with 1) less gray matter in Alzheimer disease-sensitive brain regions and 2) worse cognitive performance.

Research design and methods: Homeostasis model assessment of insulin resistance, gray matter volume, and the Rey Auditory Verbal Learning Test (RAVLT) were acquired in 372 participants at baseline and a consecutive subset of 121 individuals ~4 years later. Voxel-based morphometry and tensor-based morphometry were used, respectively, to test the association of insulin resistance with baseline brain volume and progressive gray matter atrophy.

Results: Higher insulin resistance predicted less gray matter at baseline and 4 years later in medial temporal lobe, prefrontal cortices, precuneus, and other parietal gyri. A region-of-interest analysis, independent of the voxel-wise analyses, confirmed that higher insulin resistance was related to medial temporal lobe atrophy. Atrophy itself corresponded to cognitive deficits in the RAVLT. Temporal lobe atrophy that was predicted by higher insulin resistance significantly mediated worse RAVLT encoding performance.

Conclusions: These results suggest that insulin resistance in an asymptomatic, late middle-aged cohort is associated with progressive atrophy in regions affected by early Alzheimer disease. Insulin resistance may also affect the ability to encode episodic information by negatively influencing gray matter volume in medial temporal lobe.

Figures

Figure 1
Figure 1
The relationship between higher HOMA-IR and lower regional gray matter (GM) volume for baseline images among 372 participants. Coordinates correspond to sagittal cross-sections in MNI space. An orthogonal coronal image illustrates the location of these cross-sections in the brain. The result color map and color bar represent t values. A representative voxel in parahippocampus depicts the association. Brains are oriented in neurologic space. A.U., arbitrary units. L, left. (A high-quality digital representation of this figure is available in the online issue.)
Figure 2
Figure 2
The association between higher HOMA-IR and atrophy in regional gray matter (GM) volume over ~4 years for 121 participants with longitudinal data. Coordinates correspond to sagittal cross-sections in MNI space. An orthogonal coronal image illustrates the location of these cross-sections in the brain. The color map and bar represent t values. A representative voxel in calcarine gyrus depicts the association. Brains are oriented in neurologic space. A.U., arbitrary units. R, right. (A high-quality digital representation of this figure is available in the online issue.)

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