Frisardi Vincenza, Panza Francesco, Farooqui Akhlaq A
Department of Geriatrics, Center for Aging Brain, Memory Unit, University of Bari, Bari, Italy.
Brain Res Rev. 2011 Jun 24;67(1-2):344-55. doi: 10.1016/j.brainresrev.2011.04.003. Epub 2011 Apr 28.
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.
晚年抑郁综合征常出现在轻度认知障碍、痴呆综合征和阿尔茨海默病（AD）的背景下。相反，有情绪障碍病史的患者发生认知障碍的风险更高。这两种疾病的高共病率正成为老年人群中的一个主要健康问题，这是由于它们的流行病学影响以及在残疾和死亡率增加方面的负面后果。从这个角度来看，可以推测晚年抑郁和认知障碍之间存在一种镜像关系。事实上，尽管遗传、环境和社会因素在这些疾病中的因果作用已得到广泛认可，但神经生物学联系在很大程度上仍然未知。L-谷氨酸和γ-氨基丁酸分别是中枢神经系统中主要的兴奋性和抑制性神经递质，越来越多的证据表明，这种神经递质系统的改变可能有助于将抑郁和认知障碍联系起来的神经生物学机制。在本综述文章中，我们研究了晚年抑郁综合征与AD之间关系的神经生物学基础，特别关注谷氨酸能通路信号传导，它就像连接这两种情况的一座桥梁。此外，我们还试图通过分析与这些致残性疾病相关的信号转导机制来解释谷氨酸能通路的变化、老年期抑郁和痴呆。
