Age‐Related White Matter Atrophy in the Human Brain

Abstract

Aging of the brain involves not only appreciable shrinkage of the cortex and other gray matter structures but above all loss of white matter. This could be due to a decline in the number of myelinated fibers or to a loss of water. To assess the role played by each of these factors we studied brains from 33 neurologically intact subjects at autopsy representing three different age groups: 15-50, 51-70, and 71-93 years. The precentral gyrus, gyrus rectus, and corpus callosum were selected for investigation, with staining for alkaline phosphatase on native cryostat sections to visualize the capillary network, and staining for myelin on semithin sections for nerve fiber visualization. Atrophy was objectified by measuring the number of capillaries, the intercapillary distance, and capillary length, since the capillary network remains constant throughout normal life. A mean difference of 16-20% was found, representing white matter atrophy, between the oldest and youngest age-groups. The cortex of the corresponding gyri, on the other hand, showed a difference of less than 6%. Morphometric investigation of sections stained for myelin showed that the brains with a mean age of 78.7 +/- 6.6 years had 10-15% fewer myelinated fibers. This was only partly offset by an increase in the volume of extracellular space. Our findings show that the age-related decline in brain volume is much more a question of white matter atrophy than of brain cortex atrophy. White matter atrophy could be an indirect indicator of nerve cell loss, since the volume of a nerve cell is much smaller than its myelinated fiber.

Diffusion tensor imaging and aging – a review

“…Nusbaum et al suggest that there is data to indicate that a more diffuse process in white matter may be taking place that is not necessarily confined to regions of abnormal signal intensity on conventional MR images. Correlation of the observed regional decreases in diffusion anisotropy in the genu and splenium of the corpus callosum with published findings in a histological study 28 found a loss of total nerve fiber area accompanied by an increased extracellular space with increasing age in the corpus callosum. Also noted was an interesting paper by Tang et al 29 reporting agecorrelated declines in the total volume of white matter, total volume of myelinated fibers, and total length of myelinated fibers.…”

“…White matter atrophy is most likely due to a decrease in the number (and perhaps density) of myelinated fibers, which is accompanied by an increase in extracellular space. 14 It is thought that it is the focal white matter losses of myelinated axons and gliosis that give rise to the patchy hyperintensities that are identifiable on conventional MR images. 13 In typical findings in the aged, conventional MRI studies show volume losses, enlargement of the lateral ventricles, patchy areas of abnormal signal intensity within the white matter 15 and basal ganglia, and progressive hypointensity correlating with iron deposition in the globus pallidus and putamen.…”

Quantitative fiber tracking of lateral and interhemispheric white matter systems in normal aging: Relations to timed performance

“…An anterior-posterior gradient was replicated in the commissural fiber sectors. The pattern of age-related decline of FA mirrors postmortem investigations, which reveal degradation of white matter microstructure, including degradation of myelin (measured in vivo with λT) (Kemper, 1994) and axon deletion (measured in vivo with λL) (Aboitiz et al, 1996;Meier-Ruge et al, 1992), especially of myelinated fibers of the precentral gyrus and small connecting fibers of the anterior corpus callosum. The greater susceptibility of superior than inferior and anterior than posterior fiber bundles to the throes of aging suggests a neural systems basis for dampening of components of motor control and selective attention, marking performance by healthy elderly men and women (e.g.…”

Age-related changes in human and non-human primate white matter: from myelination disturbances to cognitive decline

“…WM changes with age include a loss in volume, decreased myelin staining, and increased pallor (Kemper 1994). Histological studies have reported a 10-15% loss of myelinated fibers with age (Meier-Ruge et al 1992;Tang et al 1997;Marner et al 2003) and a decline in WM volume (Tang et al 1997;Marner et al 2003;Piguet et al 2009). While important, these studies have limitations that include variable tissue quality, small sample number, a lack of functional correlates, and a cross-sectional design that makes it difficult to discern progression and trajectory of change.…”