SEROTONIN IN AGING, LATE-LIFE DEPRESSION, AND ALZHEIMERS-DISEASE - THE EMERGING ROLE OF FUNCTIONAL IMAGING

Serotonin (5-HT) neuron and neurotransmitter loss in normal aging and neuropsychiatric diseases of late life may contribute to behavioral ch anges commonly observed in the elderly population. Extensive evidence implicates a deficit in serotonergic neurotransmission in the developm ent of major depression. It has been further suggested that the age-re lated changes in 5-HT neurons may predispose the elderly to develop de pression. There is also increasing evidence that a combination of dist urbances in cholinergic and serotonergic function may play a role in c ognitive impairment in Alzheimer's disease (AD), with serotonergic dys function potentially responsible for a significant portion of the beha vioral aspects of the disease. This implication of the 5-HT system in aging and age-related cognitive and mood disorders rests in large part on post mortem studies and animal models, which are limited in their capacity to predict dynamic human biochemical-behavior relationships o r to accurately model the living human brain. Initial applications of functional brian imaging with positron emission tomography (PET) in th e in vivo study of the brain in aging, depression, and dementia focuse d on characterizing alterations in physiological measurements of cereb ral metabolism and perfusion. However, recent advances in PET radioche mistry, instrumentation, and image processing have paved the way for n oninvasive means to test specific hypotheses regarding the direct invo lvement of 5-HT neurons in the behavioral features of aging and to def ine and monitor therapeutic regimens for neuropsychiatric conditions o f late life. Coupling of clinical trials in well-characterized subject populations with PET imaging using ligands specific for 5-HT receptor subtypes and transporter proteins promises to increase our understand ing of the role of the 5-HT system in affective and cognitive aspects of treatment response. Longitudinal studies in aging late-life depress ion, and AD are also needed to evaluate the complex interplay between neurodegenerative processes and serotonergic neurotransmission. (C) 19 98 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.