Effects of insulin resistance on white matter microstructure in middle-aged and older adults

Abstract

Objective: To investigate the potential relationship between insulin resistance (IR) and white matter (WM) microstructure using diffusion tensor imaging in cognitively healthy middle-aged and older adults.

Methods: Diffusion tensor imaging was acquired from 127 individuals (age range 41-86 years). IR was evaluated by the homeostasis model assessment of IR (HOMA-IR). Participants were divided into 2 groups based on HOMA-IR values: "high HOMA-IR" (≥2.5, n = 27) and "low HOMA-IR" (<2.5, n = 100). Cross-sectional voxel-based comparisons were performed using Tract-Based Spatial Statistics and anatomically defined regions of interest analysis.

Results: The high HOMA-IR group demonstrated decreased axial diffusivity broadly throughout the cerebral WM in areas such as the corpus callosum, corona radiata, cerebral peduncle, posterior thalamic radiation, and right superior longitudinal fasciculus, and WM underlying the frontal, parietal, and temporal lobes, as well as decreased fractional anisotropy in the body and genu of corpus callosum and parts of the superior and anterior corona radiata, compared with the low HOMA-IR group, independent of age, WM signal abnormality volume, and antihypertensive medication status. These regions additionally demonstrated linear associations between diffusion measures and HOMA-IR across all subjects, with higher HOMA-IR values being correlated with lower axial diffusivity.

Conclusions: In generally healthy adults, greater IR is associated with alterations in WM tissue integrity. These cross-sectional findings suggest that IR contributes to WM microstructural alterations in middle-aged and older adults.

Figure 1. TBSS maps of the effect of HOMA-IR on DTI parameters in middle-aged and older adults

(A) Reduced DA (light red) and FA (light blue) in the high HOMA-IR group (n = 27) compared with the low HOMA-IR group (n = 100). Purple indicates overlapping of DA and FA reduction. (B) Association between DA and HOMA-IR in all participants. Light red indicates the regions where higher HOMA-IR is associated with lower DA. The statistical maps (p < 0.05, corrected for multiple comparisons, controlling for age, white matter signal abnormality volume, and antihypertensive medication status) are thickened to aid visualization and superimposed on the Montreal Neurological Institute template image. DA = axial diffusivity; DTI = diffusion tensor imaging; FA = fractional anisotropy; HOMA-IR = homeostasis model assessment of insulin resistance; TBSS = Tract-Based Spatial Statistics.

Figure 2. Scatter plots demonstrating the association between mean DA and HOMA-IR values

Mean DA was extracted within clusters resulting from the Tract-Based Spatial Statistics maps (p < 0.05, corrected for multiple comparisons, controlling for age, WM signal abnormality volume, and antihypertensive medication status) demonstrating high vs low HOMA-IR group comparisons (figure 1A). White circles indicate individuals on antihypertensive medication, and black circles indicate individuals not on medication. The vertical reference dotted line depicts the cutoff between low and high HOMA-IR levels. DA = axial diffusivity; HOMA-IR = homeostasis model assessment of insulin resistance; WM = white matter.