The brain

Virtually every major neurodegenerative illness becomes more common with age, with most seen chiefly in old age. This chapter views ageing as a stochastic process of deficit accumulation, in which, on average, things gradually function less effectively. This on-average decline is mitigated by the fact that change typically happens slowly and that some improvement is also possible at any time. The chapter explores that brain ageing results from changes to the metabolic triad of altered mitochondrial functioning, reactive oxygen species formation and altered intracellular calcium homeostasis; together, these ultimately impair homeostatic responses. Ageing represents the accumulation of unrepaired sub-cellular damage, which eventually compromises the functioning of cells, tissues and organs that becomes at some stage clinically evident. As the brain ages, neuronal energy supplies primarily generated in the mitochondria decrease. The ageing brain undergoes structural and functional changes that manifest clinically as alterations in everyday performance but that are typically more visible with formal testing.