AGING, NEURODEGENERATIVE DISEASE AND THE BRAIN

The brain undergoes many changes in chemistry and structure during nor mal aging. For example, it dries and shrinks. Neurons are lost from so me regions and there is also neuronal atrophy and loss of synaptic bra nching. The extent of such losses remains controversial for all but a few subcortical regions of the brain. Decreases in glucose metabolism and in some pre- and post-synaptic neurotransmitter indices have also been reported. Many systems, however, remain entirely unexplored. The evidence to date also indicates that there is great regional specifici ty in the effects, and that humans show considerable variability betwe en individuals. Of interest is the fact that some of the changes most clearly demonstrated in normal aging - such as loss of dopaminergic ne urons of the substantia nigra and cholinergic neurons of the medial ba sal forebrain - also occur in a much accentuated form in neurodegenera tive diseases such as Parkinson's disease and Alzheimer disease. The s mall loss of these systems in normal aging may account for the shuffli ng gait, stooped posture and memory loss in the elderly. A phenomenon seen in neurodegenerative diseases, but not in normal aging, is the ap pearance of chronic inflammation in the brain. The suggestion that the progress of such diseases might be slowed by treatment with anti-infl ammatory agents has, in the case of Alzheimer disease, gained some sup port from 19 epidemiological studies and one very small clinical trial . Clearly more detailed clinical trials are required, and caution must be used because of the undesirable side effects of currently availabl e anti-inflammatory agents.