LIFE AND DEATH OF NEURONS IN THE AGING BRAIN

Neurodegenerative disorders are characterized by extensive neuron deat h that leads to functional decline, but the neurobiological correlates of functional decline in normal aging ave less well defined. For deca des, it has been a commonly held notion that widespread neuron death i n the neocortex and hippocampus is an inevitable concomitant of brain aging, but recent quantitative studies suggest that neuron death is re stricted in normal aging and unlikely to account for age-related impai rment of neocortical and hippocampal functions, In this article, the q ualitative and quantitative differences between aging and Alzheimer's disease with respect to neuron loss are discussed, and age-related cha nges in functional and biochemical attributes of hippocampal circuits that might mediate functional decline in the absence of neuron death a re explored. When these data are viewed comprehensively, it appears th at the primary neurobiological substrates for functional impairment in aging differ in important ways from those in neurodegenerative disord ers such as Alzheimer's disease.