Marked loss of myelinated nerve fibers in the human brain with age

The white matter is the structure of the brain that declines most with age—almost 30%, but little is known about the age‐effect on the fibers that constitute the white matter. In the present study, the total length of myelinated fibers was measured with a newly developed stereologic method. Specimens came from 36 normal Danes (18 males and 18 females) with an age ranging between 18 and 93 years. Samples were taken systematically and randomly from the white matter, and the biopsy specimens were randomly rotated before sectioning to avoid bias due to the anisotropic nature of nerve fibers. The fibers were counted at light microscopic level at approximately 10,000× magnification, and the diameter of each counted fiber was measured to get the diameter distribution. Males were found to have a total myelinated fiber length of 176,000 km at the age of 20 and 97,200 km at the age of 80, whereas the total length in females was 149,000 km at the age of 20 and 82,000 km at the age of 80. This finding corresponds to a 10% decrease per decade or a total decrease of 45% from the age of 20 to 80 years, and a sex difference of 16%. The fiber diameter distribution showed that primarily the thinner fibers were lost with a relative preservation of the thicker ones. The marked loss of myelinated nerve fibers with age could explain some of the cognitive decline seen in the elderly. J. Comp. Neurol. 462:144–152, 2003. © 2003 Wiley‐Liss, Inc.