ABSTRACT
More than any other organ of the body, we are concerned with the ageing of the brain. The ageing brain must be considered a special case within the domain of ageing. While age-related changes in the brain in general parallel those of the body, there are important exceptions. Brain diseases that are usually regarded as concomitants of old age, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) are sometimes seen in the young, and most elderly individuals manage to evade them. It is not uncommon to see a very active mind in a frail old body. Our examination of the ageing of the brain must therefore occur in the context of a neurobiological understanding. The ageing brain is a special case also for social reasons. An epidemic of dementia is upon us, and governments in the developed world are preoccupied with the impact this will have on the society of the future. As Professor Broe states later in this book, we are in the Age of Neurodegenerative Disorders, and insights into the mechanisms of ageing are urgently needed. . In the face of this dread, we must take heart in the pace of neuroscientific research, which has been breathless indeed. Let us consider a few examples. Most studies both in vivo and post mortem, suggest shrinkage of the adult brain as it ages, with a reported reduction of about 5% in brain weight per decade after the age of 40 years.2 This change is not uniform, however, with the prefrontal regions being affected more than the temporal and parietal neocortex. In the subcortical regions, the neostriatum atrophies moderately with age, while the globus pallidum and thalamus are relatively spared.3 What we do not understand are the reasons for this variation. Why is the substantia nigra, for example, more susceptible to age-related degeneration than the thalamus? What are the determinants of hippocampal degeneration seen in ageing brains? Questions such as this may be the keys to understanding the physiological processes involved in brain ageing. It is quite likely that the mechanisms of neural ageing are the same as for the rest of the body. There must also be important differences. A large part of the human genome is involved in brain development, suggesting that a great complexity must be fathomed. It was thought for many years that the changes in brain volume seen in ageing were a consequence of age-related neuronal loss.4 This notion was so well accepted that it had entered lay parlance. Recent studies using better stereological methods have shown that this may not be true, and in fact most brain regions do not suffer an age-related neuronal loss.5 If there is a sparing of the total number of cortical neurones, what is the basis of loss of cortical volume with ageing? The hippocampus has been studied extensively to understand this, and it has been shown that its functional organization is altered with ageing. This is related to alterations in connectivity, because of reductions in dendrites and synapses. In both rodents and humans, changes have been reported in dendritic arbor, spines and synapse morphology that could impact on the function of hippocampal circuits but would not be reflected as neuronal loss.6 This is functionally important as the most cognitively impaired aged rats demonstrate the greatest degree of abnormality.
