Late-life depression and Alzheimer's disease: the glutamatergic system inside of this mirror relationship

Late-life depressive syndromes often arise in the context of predementia, dementia syndromes, and Alzheimer's disease (AD). Conversely, patients with a history of mood disorders are at higher risk of developing cognitive impairment. The high rate of co-occurrence of these two disorders is becoming a major health problem in older subjects for both their epidemiological impact and the negative outcomes in terms of disability and increased mortality. In this perspective, it is possible to speculate on the presence of a mirror relationship between depressive and cognitive disorders in late-life. Indeed, although a causal contribution of genetic, environmental, and social factors is widely recognized in these disorders, the neurobiological links still remain largely unknown. l-glutamic acid and γ-aminobutyric acid are the principal excitatory and inhibitory neurotransmitters in the central nervous system, respectively, and increasing evidence suggests that alterations in this neurotransmitter system may contribute to the neurobiology linking depression and cognitive impairment. In the present review article, we examined the neurobiological bases of the relationship between late-life depressive syndromes and AD, with a particular attention to glutamatergic pathway signalling like a bridge connecting these two conditions. In addition, attempts have been made to explain changes in glutamatergic pathway, depression in older age, and dementia through the analysis of signal transduction mechanisms associated with these disabling disorders.