Serotonin in Aging, Late-Life Depression, and Alzheimer's Disease: The Emerging Role of Functional Imaging

Abstract

(5-HT) neuron and neurotransmitter loss in normal aging and neuropsychiatric diseases of late life may contribute to behavioral changes commonly observed in the elderly population. Extensive evidence implicates a deficit in serotonergic neurotransmission in the development of major depression. It has been further suggested that the agerelated changes in 5-HT neurons may predispose the elderly to develop depression. There is also increasing evidence that a combination of disturbances in cholinergic and serotonergic function may play a role in cognitive impairment in Alzheimer's disease (AD), with serotonergic dysfunction potentially responsible for a significant portion of the behavioral 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 or to accurately model the living human brain. Initial applications of functional brian imaging with positron emission tomography (PET) in the in vivo study of the brain in aging, depression, and dementia focused on characterizing alterations in physiological measurements of cerebral metabolism and perfusion. However, recent advances in PET radiochemistry, instrumentation, and image processing have paved the way for noninvasive means to test specific hypotheses regarding the direct involvement of 5-HT neurons in the behavioralMajor depression in late life and Alzheimer's disease (AD) are disorders of enormous and increasing public health significance. The prevalence of major depression is estimated at 1% to 10% of persons 60 years of age or older, whereas depressive symptoms may occur in up to 20% (Blazer et al. 1987; Borson et al. 1986; Casey 1994). Substantially higher rates of both major and minor depressions occur among institutionalized aged persons (Parmelee et al. 1989). Furthermore, the rate of suicide in this age group is higher than at any other Address correspondence to: Carolyn Cidis Meltzer, M.D., University of Pittsburgh Medical Center, PET Facility, B-938, 200 Lothrop Street, Pittsburgh, PA 15213-2582. Received March 6, 1997 accepted October 3, 1997. 408 C.C. Meltzer et al.N EUROPSYCHOPHARMACOLOGY 1998 -VOL . 18 , NO . 6 stage of life (Casey 1994). Psychosocial issues such as bereavement, disability, and declining health may serve as contributing factors in the development of geriatric depression (Casey 1994;Gilewski et al. 1991;Kennedy et al. 1991). Ad is truly a disorder of aging, with an incidence of 5% in persons older than 65 years and doubling of disease prevalence every 5 years after age 65; affected individuals represent 20% to 50% of the population after age 80 (Cross and Gurland 1986) (Evans et al. 1989). Costs associated with dementia burden exceed $90 billion annually in the United States (Ernst and Hay 1994). Depression is commonly seen in AD patients and may further interfere with cognitive function, as well as substantially...

Platelet serotonin concentration and monoamine oxidase type B activity in female patients in early, middle and late phase of Alzheimer's disease

“…It has been shown that CSF biomarkers of AD (beta-amyloid 1-42, total tau and tau phosphorylated at threonine 181) differ according to age, suggesting that AD pathology might differ between young and old patients (Bouwman et al 2008, Meltzer et al 1998. In our study patients and controls were matched for age and the age range was similar for all groups.…”

Neuronal Tryptophan Hydroxylase mRNA Expression in the Human Dorsal and Median Raphe Nuclei: Major Depression and Suicide

“…Serotonergic receptor binding in the cortex, specifically 5HT 1A , 5HT 1B/D , and 5HT 2A , has been found to be decreased postmortem in elderly suicides and some of these findings have been confirmed in depressed elderly patients in PET studies (Meltzer et al (1998b) and also reviewed in Meltzer et al (1998a)). Therefore, it is likely that changes in serotonergic neurotransmission that are associated with depression and suicide are only exacerbated in the elderly.…”

Long-term neuropsychological effects of ecstasy in middle-aged ecstasy/polydrug users

“…In addition, the modulation by serotonin of other neurotransmitters like acetylcholine seems to decrease with age (Richter-Levin and Segal 1996). These and other biochemical changes are associated with age-related memory decline and depression (Meltzer et al 1998). Alzheimer's disease, with memory impairment as a main symptom, is also associated with reductions in 5-HT (Lai et al 2005) and with a cholinergic-serotonergic imbalance (GarciaAlloza et al 2005;Meltzer et al 1998).…”

“…Little is known about the effect of ecstasy on memory and mood later in life. With increasing age, serotonin levels and the number of serotonin receptors gradually reduce (Goldberg et al 2004;McEntee and Crook 1991;Meltzer et al 1998;Meneses 1999). In addition, the modulation by serotonin of other neurotransmitters like acetylcholine seems to decrease with age (Richter-Levin and Segal 1996).…”

“…These and other biochemical changes are associated with age-related memory decline and depression (Meltzer et al 1998). Alzheimer's disease, with memory impairment as a main symptom, is also associated with reductions in 5-HT (Lai et al 2005) and with a cholinergic-serotonergic imbalance (GarciaAlloza et al 2005;Meltzer et al 1998). While depressive symptoms seem to increase with age, impulsivity and sensation seeking are thought to dwindle with age (Zuckerman 1994).…”