Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL, 60611, USA.
Department of Biology, West Virginia State University Institute, WV-25112, USA.
Neurosci Lett. 2019 Jun 21;704:36-44. doi: 10.1016/j.neulet.2019.03.050. Epub 2019 Apr 1.
Behavioral and Psychological Symptoms of Dementia (BPSD), present in almost 90% of patients with Alzheimer's Disease (AD), cause extensive impairment leading to reduced independence and inability to complete activities of daily living. Though BPSD includes a wide range of symptoms, such as agitation, aggression, disinhibition, anxiety, depression, apathy, delusions, and hallucinations. Certain BPSD in AD co-present and can be clustered into distinct domains based on their frequency of co-occurrence. As these BPSD are so pervasive in any stages of AD, the disease may be better characterized as a disorder of heterogeneous degenerative symptoms across a number of symptom domains, with the most prominent domain comprising memory and cognitive deficits. Importantly, there are no FDA-approved drugs to treat these BPSD, and new approaches must be considered to develop effective treatments for AD patients. The biogenic monoamine 5-hydroxytryptamine (5-HT), or serotonin, works as both a neurotransmitter and neuromodulator, which has been tied to cognitive decline and multiple BPSD domains. This review summarizes the evidence for specific serotonergic system alterations across some of the well-studied cognitive, behavioral, and psychiatric domains. Though differences in overall serotonergic transmission occur in AD, circuit-specific alterations in individual 5-HT receptors (5-HTRs) are likely linked to the heterogeneous presentation of BPSD in AD.
痴呆的行为和心理症状（BPSD），几乎存在于 90%的阿尔茨海默病（AD）患者中，导致广泛的损伤，导致独立性降低和无法完成日常生活活动。虽然 BPSD 包括广泛的症状，如躁动、攻击、抑制障碍、焦虑、抑郁、冷漠、妄想和幻觉。AD 中的某些 BPSD 同时存在，并可以根据其共同发生的频率聚类为不同的领域。由于这些 BPSD 在 AD 的任何阶段都如此普遍，因此该疾病可能更好地被描述为一种在多个症状领域存在异质退行性症状的障碍，其中最突出的领域包括记忆和认知缺陷。重要的是，目前没有 FDA 批准的药物来治疗这些 BPSD，必须考虑新的方法来为 AD 患者开发有效的治疗方法。生物单胺 5-羟色胺（5-HT）或血清素既是神经递质又是神经调质，与认知能力下降和多种 BPSD 领域有关。本综述总结了一些经过充分研究的认知、行为和精神领域中特定 5-羟色胺能系统改变的证据。尽管 AD 中存在总体 5-羟色胺传递的差异，但个体 5-羟色胺受体（5-HTRs）的特定回路改变可能与 AD 中 BPSD 的异质表现有关。
