Changes in the ageing brain in health and disease.

The brains of individuals, who are cognitively normal, show age-related changes that include an overall reduction in brain volume and weight, which are associated with gyral atrophy and widening of the sulci of the cerebral cortex, and enlargement of the brain ventricles. These changes are partly the result of nerve cell loss but accurate estimates of neuronal loss are notoriously difficult to make. Microscopically, there are increasing amounts of the age-related pigment, lipofuscin, granulovacuolar degeneration in neurones, Hirano bodies, variable amounts of diffuse deposits of beta-amyloid in the parenchyma, the presence of neurofibrillary tangles mainly confined to the hippocampus and amygdala, and sparse numbers of senile plaques in these brain regions and also in other cortical areas. Of these changes, neurofibrillary tangles and senile plaques are the neuropathological hallmark of Alzheimer's disease in which they are more abundant and widespread. Alzheimer's disease has therefore been regarded as accelerated brain ageing; however, the realization that there is a strong genetic contribution to developing the disease at least implies that it may not be the inevitable, even if frequent, consequence of old age. Understanding the molecular basis of plaque and tangle formation is advancing greatly and is the main focus of research into the cellular and molecular changes observed in the ageing brain.