Brain structure changes over time in normal and mildly impaired aged persons

Abstract

Structural brain changes in aging are known to occur even in the absence of dementia, but the magnitudes and regions involved vary between studies. To further characterize these changes, we analyzed paired MRI images acquired with identical protocols and scanner over a median 5.8-year interval. The normal study group comprised 78 elders (25M 53F, baseline age range 70-78 years) who underwent an annual standardized expert assessment of cognition and health and who maintained normal cognition for the duration of the study. We found a longitudinal grey matter (GM) loss rate of 2.56 ± 0.07 ml/year (0.20 ± 0.04%/year) and a cerebrospinal fluid (CSF) expansion rate of 2.97 ± 0.07 ml/year (0.22 ± 0.04%/year). Hippocampal volume loss rate was higher than the GM and CSF global rates, 0.0114 ± 0.0004 ml/year (0.49 ± 0.04%/year). Regions of greatest GM loss were posterior inferior frontal lobe, medial parietal lobe and dorsal cerebellum. Rates of GM loss and CSF expansion were on the low end of the range of other published values, perhaps due to the relatively good health of the elder volunteers in this study. An additional smaller group of 6 subjects diagnosed with MCI at baseline were followed as well, and comparisons were made with the normal group in terms of both global and regional GM loss and CSF expansion rates. An increased rate of GM loss was found in the hippocampus bilaterally for the MCI group.

Keywords: CSF expansion; aging; cognition; grey matter loss; hippocampal volume loss.

Figure 1.. A. Composite scans used for paired longitudinal registration. Composite images have high T1-like contrast derived by combining GM, WM and CSF segmentation probability maps in native space (see text). Initial (a) and repeat (b) scans were often acquired at different orientations. The average image (c) represents the symmetric transformation of a & b into a common image space. B. Averaged shrinkage rate (d) and expansion rate (e) across all 84 subjects, demonstrating widespread GM loss in cortical and subcortical regions (d), and expansion in ventricular and sulcal CSF (e).

Figure 2.. A. Map of decreases in regional GM volume over 5.8 years in 69 subjects normal at both time points. Regional volume loss is seen in ventral posterior frontal lobe, temporal pole, dorsal cerebellum and midbrain grey matter. Significance threshold is p = 0.00001; Family-wise error correction threshold was t = 5.1, indicated by the black arrowhead on the scale shown on the left. B. Increases in regional grey matter volume loss rates in baseline-diagnosed MCI compared to subjects diagnosed as normal at both baseline and repeat study (5.8 years later). Anterior hippocampus demonstrates significant excess volume loss during the MCI to AD transition (threshold p = 0.00001).