Brain ageing and dementia

In some diseases of the nervous system there is a satisfyingly complete chain between clinical disorder, distribution and nature of the lesions, underlying biochemical causes and consequences, and thus a rational treatment. There are also too many others in which understanding of these steps is minimal, even as far as uncertainty about where studies of aetiology and pathogenesis should begin. Such difficulties are well shown by the associations suggested between the effects of ageing on the brain and certain forms of dementia. On the one hand are the problems, verging on the philosophical, of defining 'age', both as a general biological phenomenon (Comfort, 1964), and as the terminal phase in the development of a particular organ; and on the other is the need in clinical practice among elderly patients to disentangle intrinsic aspects of senescence from probable extraneous factors, such as arteriosclerosis. Both may be 'worse confounded' should an attempt be made to correlate the dementia with the distribution of the various types of lesions found in the brain. In the circumstances, as the links between ageing and dementia are not clear, perhaps the best that can be done is to establish the questions required to evaluate what is common to the brain in these two conditions. Any such analysis is biased by the inquirer's own frame of reference, so the reader should beware of the underlying trends here of concentration on organic lesions, and the morbid anatomist's reluctant awareness of significant lesions at a biochemical or functional level that cannot be demonstrated by the most sophisticated histological technique. It seems profitable to ask about the nature of 'intrinsic' ageing processes in the brain; the relative importance of dementia and other psychiatric disorders in later life and how they can be assessed; what are the known structural or biochemical changes in the brains of affected patients; whether they can be correlated in any way with the intellectual disorders; what reasonable grounds exist for predicting the nature or sites of as yet unidentified lesions, and thus where and how to look for them; and, lastly, if lesions found in dementia resemble those found in normal ageing, has their similarity any significance for attempts to prolong human life ? The biological importance of ageing has been a subject of seemingly infinite appeal, both to philosophical and pragmatic biologists, and they have yet to agree about much of what they have studied. Medawar (1952) and Comfort (1964) may be taken as guides to modern ideas about aspects of ageing through the animal kingdom. The gulfs between their theoretical analyses, hypotheses of generalized mechanisms of senescence (a concept that itself begs many questions, for why should all tissues be expected to age in the same way or by the same mechanism ? ), and pathological findings in cells and tissues have been discussed in general by Rowlatt and Franks (1973), and in the brain in particular by Dayan (1972). If the strength of a scientific theory lies in its generality, simplicity, and clarity, then it may safely be concluded that no universal mechanism of senescence has yet been proven (Goldstein, 1971)—for example, errors in protein synthesis, immunological crises, auto-oxidation, and abnormal cross-linking of proteins have all been demonstrated in restricted circumstances, and slow viruses have been invoked for no very good reason, but none has been shown to be applicable to the brain. Valuable though senescence may be to the impartial and remote guardian of evolution, its physical meaning at the level of organism or cell remains in doubt. More is known about the morphological lesions found in elderly man. Pathological changes in the brain in normal aged people have been discussed by Gellerstedt (1933) and Tomlinson et al. (1968), and reviewed by Dayan (1973). There is general agreement about overall loss of weight of the brain, though not about its cause, and about histological lesions that may be divided into the important and the trivial. The former include intraneuronal neurofibrillary tangles and argyrophilic (senile) plaques in the cortical neuropil, and perhaps amyloid deposits around superficial cortical and pial blood