Relationship among neuroimaging indices of cerebral health during normal aging

Abstract

Sensitive measures of brain aging show great promise for gauging factors that affect aging and degenerative processes, such as risk genes or therapy. Here we examined age-related trends for three indices of cerebral health: gyral gray matter (GM) thickness, dilation of sulcal spaces with CSF, and the volume of T2-hyperintense white matter (HWM) lesions. The study involved 31 healthy adults age 57-82 years old. Measurements of average GM thickness, average sulcal span and HWM volume were performed using high-resolution 3D T1- and T2-weighted brain MR images. Age-related trends for the three cerebral health indices were consistent with previously published work though the analysis of their covariance led to a previously unreported relationship. Simultaneous multiple regression found that dilation of cortical sulci were primarily (t = 2.59, P < 0.01) related to the increases in HWM volume and secondarily related (t = -2.51, P < 0.01) to the reductions of the cortical GM thickness. The are-corrected correlation between reduction in GM thickness and increases in HWM volume, was not significant (P = 0.34). These findings are of interest in designing quantitative measures of brain aging for monitoring individual patients and in large-scale clinical trials.

Figure 1

T1‐weighted image processing pipeline consists of skull stripping (A); spatial normalization, RF homogeneity correction and tissue segmentation (B); extraction of GM and WM surfaces (C,D); extraction of sulcal folds (E), and automated labeling of sulci (F).

Figure 2

Measurement of indices of cortical health: average sulcal span and average gyral GM thickness. Average sulcal span was defined as an average 3D distance between opposing gyral banks along the normal projections to the medial sulcal mesh. New tracings, normal to the exterior GM mesh, were started at the intersections between normal projections to the sulcal mesh. The average gyral GM thickness was defined as an average 3D distance from the outer GM mesh to the inner cortical WM mesh.

Figure 3

Linear (r) and age‐corrected partial (pr) correlation coefficients are illustrated among age and three indices of cerebral health. *Indicates statistically significant correlations (P < 0.01).

Figure 4

Cerebral health indices vs. age: average sulcal span (top), GM thickness (middle), and HWM volume (bottom).

Figure 5

Age‐corrected relationship between sulcal span and HWM volume. The solid line corresponds to the initial (0–1 cm³) increase in HWM volumes and dotted line the later (1 cm³ and up) increase in HWM volumes.

Figure 6

Age‐corrected relationship between cortical health indices: average sulcal span is plotted vs. average GM thickness.

Figure 7

Age‐corrected relationship between GM thickness and HWM volume.