Trajectories of brain aging in middle-aged and older adults: regional and individual differences

Abstract

The human brain changes with age. However, the rate and the trajectories of change vary among the brain regions and among individuals, and the reasons for these differences are unclear. In a sample of healthy middle-aged and older adults, we examined mean volume change and individual differences in the rate of change in 12 regional brain volumes over approximately 30 months. In addition to the baseline assessment, there were two follow-ups, 15 months apart. We observed significant average shrinkage of the hippocampus, entorhinal cortex, orbital-frontal cortex, and cerebellum in each of the intervals. Shrinkage of the hippocampus accelerated with time, whereas shrinkage of the caudate nucleus, prefrontal subcortical white matter, and corpus callosum emerged only at the second follow-up. Throughout both assessment intervals, the mean volumes of the lateral prefrontal and primary visual cortices, putamen, and pons did not change. Significant individual differences in shrinkage rates were observed in the lateral prefrontal cortex, the cerebellum, and all the white matter regions throughout the study, whereas additional regions (medial-temporal structures, the insula, and the basal ganglia) showed significant individual variation in change during the second follow-up. No individual variability was noted in the change of orbital frontal and visual cortices. In two white matter regions, we were able to identify factors associated with individual differences in brain shrinkage. In corpus callosum, shrinkage rate was greater in persons with hypertension, and in the pons, women and carriers of the ApoEepsilon4 allele exhibited declines not noted in the whole sample.

Fig. 1

Examples of manual tracings of neocortical and limbic regions of interest. (A) Lateral and orbito-frontal cortex, (B) primary visual (pericalcarine) cortex, (C) insula, (D) hippocampus, and (E) entorhinal cortex.

Fig. 2

Examples of manual tracings of the caudate nucleus and putamen (A), corpus callosum and pons (B), and cerebellar hemispheres (C).

Fig. 3

Longitudinal changes and age-related differences (regression line) in volumes of four cortical regions. Volumes are adjusted for the intracranial volume measured at the same occasion.

Fig. 4

Longitudinal changes and age-related differences (regression line) in volumes of the medial temporal regions (hippocampus and the entorhinal cortex). Volumes are adjusted for the intracranial volume measured at the same occasion.

Fig. 5

Longitudinal changes and age-related differences in volumes of the neostriatum (caudate and putamen) and the cerebellum. Volumes are adjusted for the intracranial volume measured at the same occasion.

Fig. 6

Longitudinal changes and age-related differences in volumes of the white matter regions. Volumes are adjusted for the intracranial volume measured at the same occasion.

Fig. 7

Changes in regional brain volumes in two follow-up intervals. Annual percent of change is the difference between two volumes divided by the one that was measured earlier between the two and by the length of the interval between the measurements. The bars are standard errors of the means.