A voxel-based morphometric study of ageing in 465 normal adult human brains.

Normal Cognitive Aging

Differential aging of the brain: Patterns, cognitive correlates and modifiers

Age-related myelin breakdown: a developmental model of cognitive decline and Alzheimer’s disease

The structure of the brain is constantly changing from birth throughout the lifetime, meaning that normal aging, free from dementia, is associated with structural brain changes. This paper reviews recent evidence from magnetic resonance imaging (MRI) studies about age-related changes in the brain. The main conclusions are that (1) the brain shrinks in volume and the ventricular system expands in healthy aging. However, the pattern of changes is highly heterogeneous, with the largest changes seen in the frontal and temporal cortex, and in the putamen, thalamus, and accumbens. With modern approaches to analysis of MRI data, changes in cortical thickness and subcortical volume can be tracked over periods as short as one year, with annual reductions of between 0.5% and 1.0% in most brain areas. (2) The volumetric brain reductions in healthy aging are likely only to a minor extent related to neuronal loss. Rather, shrinkage of neurons, reductions of synaptic spines, and lower numbers of synapses probably account for the reductions in grey matter. In addition, the length of myelinated axons is greatly reduced, up to almost 50%. (3) Reductions in specific cognitive abilities--for instance processing speed, executive functions, and episodic memory--are seen in healthy aging. Such reductions are to a substantial degree mediated by neuroanatomical changes, meaning that between 25% and 100% of the differences between young and old participants in selected cognitive functions can be explained by group differences in structural brain characteristics.

Structural brain changes in aging: courses, causes and cognitive consequences.

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.

Age‐Related White Matter Atrophy in the Human Brain

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Age‐Related White Matter Atrophy in the Human Brain