BEHAVIORAL AND NEURAL BIOLOGY 31, 115-172 (1981) REVIEW Age-Related Behavioral and Neurobiological Changes: A Review with an Emphasis on Memory PATRICIA KUBANIS 1 AND STEVEN F. ZORNETZER z Department of Neuroscience, University of Florida, Gainesville, Florida 32610 This review focuses on age-related memory loss and its neurobiological corre- lates. A considerable body of evidence indicates that performance on tests of learning and memory declines with increasing age. Performance decrements have been documented in both human and animal studies employing tests of short- and long-term memory. In reviewing this voluminous literature, we have attempted to identify the critical factors accounting for the task-selective nature of these de- ficits. Important variables include task complexity, attention, and situational pacing requirements. Neurobiological changes associated with aging appear to be specific to particular anatomical regions and neurotransmitter systems. Most experimental interest has been directed toward the role of dopamine and acetyl- choline in relation to memory deficits associated with aging. Norepinephrine has frequently been implicated in processes related to memory, including arousal, attention, and neural plasticity. In view of the role of norepinephrine in memory- related functions, we suggest that noradrenergic involvement in age-related mem- ory dysfunction should receive more serious consideration. Contents. L Memory Deficits with Aging. A. Short-term memory. 1. Human studies. 2. Animal studies. 3. Conclusions on short-term memory. B. Long-term memory. 1. Human studies. 2. Animal studies. 3. Conclusions on long-term memory. H. Neurobiological Changes with Aging. A. Neuroanatomical changes. I. Gross morphology. 2. Selective neuronal loss. 3. lntracellular accumulation of substances. 4. Cellular morphology. 5. Synaptic number. 6. Astrocytic hyper- trophy. 7. Neural metabolism and the microenvironment of neurons. 8. Reactive synaptogenesis. B. Neurophysiological changes. C. Neurochemical and hormonal function. 1. Neurotransmitters. 2. Hypothalamic-pituitary-adrenal function. 3. Arousal. IlL Summary and Conclusions. The neurobiological basis of memory and the neurobiological changes associated with aging have, until recently, been independent subjects Address correspondence and reprint requests to Patricia Kubanis, Department of Neuroscience, Box J-244, JHMHC, University of Florida, College of Medicine, Gainesville, FL 32610. The authors wish to thank W. C. Abraham, J. A. Bralley, and R. L. Delanoy for their contributions to an earlier manuscript from which the present review evolved. Helpful critical comments by W. C. Abraham are also gratefully acknowledged. 115 0163-1047/81/02115-58502.00/0 Copyright © 1981 by Academic Press, Inc. All rights of reproduction in any form reserved.