Aging brains lose their connections

Healthy aging is characterized by a gradual decline in cognitive function. Mental processes such as attention, memory and the ability to process information are at their peak when people are in their 30s and 40s, but as we get older, we find it increasingly difficult to focus on relevant information and to recall the names of familiar objects or people, and it takes us longer to perform mental tasks.

This age-related cognitive decline varies greatly between individuals. Some people experience little change or none at all, while others go on to develop Alzheimer's Disease or other forms of dementia. For most of us, the degree of cognitive decline will be small and therefore will not affect the way we live our lives.

Little is known about the neurobiological basis of these changes, but they are generally attributed to the degeneration of gray matter in the cerebral cortex. Aging is usually correlated with a reduction in the total volume of gray matter, and memory deficits with deterioration of the hippocampus. But a new study suggests that age-related cognitive impairments may instead arise from degeneration of white matter tracts, which contain the nerve fibres connecting different regions of the brain.

David Ziegler and his colleagues of the Department of Brain and Cognitive Sciences at MIT sought to investigate whether gray and white matter are affected differently in aging, and to whether either is more closely associated to age-related changes in cognitive performance. They recruited 36 young adults (aged 18-28) and 38 older adults (aged 61-86) for the study; all of these participants were healthy - none of them had any history of psychiatric or neurological disorders, and all performed well on the Mini Mental State Examination (MMSE), which is used to screen for dementia.

To address the first question, the researchers used high-resolution structural fMRI to measure the thickness of the cererbal cortex in their participants. The same data were then used to perform diffusion tensor imaging, a recently developed technique, based on the diffusion of water molecules, which measures the integrity of white matter tracts in the brain. Finally, a series of tests was administered to the participants, to measure three different mental processes: cognitive control (or "executive function"), semantic memory (or memory for meaning) and episodic memory (or memory for life events).

Structural fMRI reveals differences in white matter integrity between healthy young and older participants. Regions shown in red-yellow indicate areas where the signal was smaller in older participants compared to younger ones, and regions in blue indicate where the signal was larger in the older participants. (From Ziegler et al, 2008)

The neuroimaging showed significant differences in both gray matter thinning and white matter density between the young and older participants. However, whereas thinning of the  cerebral cortex was restricted to sensory and motor areas, the reducted white matter integrity in the group of older participants, was more widespread, and included the fibre tracts lying underneath the frontal, temporal and parietal lobes, as well as the corpus callosum, the huge bundle of approximately 100 million nerve fibres which connects the two hemispheres of the brain. Statistical analyses also revealed a major effect of age - the older was the participant, the greater the oberved reduction in white matetr volume.

The researchers then tested for a correlation between cortical thickness, white matter density and performance on the cognitive tests. strong positive correlation between the integrity of the white matter underlying the frontal cortex and performance on the cognitive control test. On the other hand, performance on the episodic memory test was positively correlated with white matter integrity in the temporal and parietal, but not frontal, cortex. By contrast, no strong correlations were found between gray matter thickness and performance on any of the tests.

Thus, healthy aging is accompanied by reductions in both gray matter thickness and white matter integrity. Both of these findings have been reported before, but this is the first study to show that age-related cognitive decline is more strongly correlated with the latter than with the former. The study is in line with other studies which show that small diameter myelinated nerve fibres are more susceptible to aging than larger ones. The corpus callosum is believed to consist mostly of small diameter fibres, as are the other white matter tracts which were seen here to be reduced in integrity.

The changes in white matter density may occur as a result of abnormalities in myelin, the fatty protein which is synthesized by glial cells and which wraps itself around nerve fibres in multiple layers, to increase the velocity at which they conduct impulses. Animal experiments have shown that, with aging, deposits in the myelin sheath cause the layers to split. This leads to the formation of holes within the sheath, which accumulate and ultimately interefere with nerve cell function. Although they provide no direct evidence for it, the authors suggest that these processes occur in healthy human aging, and are responsible for the observed differences in cognitive performance.

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Ziegler, D. A. et al (2008). Cognition in healthy aging is related to regional white matter integrity, but not cortical thickness Neurobiol. Aging. DOI: 10.1016/j.neurobiolaging.2008.10.015