The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY, USA ; Zucker Hillside Hospital, Hofstra North Shore-Long Island Jewish School of Medicine, Glen Oaks, NY, USA.
Zucker Hillside Hospital, Hofstra North Shore-Long Island Jewish School of Medicine, Glen Oaks, NY, USA.
Neuropsychiatr Dis Treat. 2014 Nov 24;10:2253-62. doi: 10.2147/NDT.S60837. eCollection 2014.
Psychotic symptoms emerging in the context of neurodegeneration as a consequence of Alzheimer's disease was recognized and documented by Alois Alzheimer himself in his description of the first reported case of the disease. Over a quarter of a century ago, in the context of attempting to develop prognostic markers of disease progression, psychosis was identified as an independent predictor of a more-rapid cognitive decline. This finding has been subsequently well replicated, rendering psychotic symptoms an important area of exploration in clinical history taking - above and beyond treatment necessity - as their presence has prognostic significance. Further, there is now a rapidly accreting body of research that suggests that psychosis in Alzheimer's disease (AD+P) is a heritable disease subtype that enjoys neuropathological specificity and localization. There is now hope that the elucidation of the neurobiology of the syndrome will pave the way to translational research eventuating in new treatments. To date, however, the primary treatments employed in alleviating the suffering caused by AD+P are the atypical antipsychotics. These agents are approved by the US Food and Drug Administration for the treatment of schizophrenia, but they have only marginal efficacy in treating AD+P and are associated with troubling levels of morbidity and mortality. For clinical approaches to AD+P to be optimized, this syndrome must be disentangled from other primary psychotic disorders, and recent scientific advances must be translated into disease-specific therapeutic interventions. Here we provide a review of atypical antipsychotic efficacy in AD+P, followed by an overview of critical neurobiological observations that point towards a frontal, tau-mediated model of disease, and we suggest a new preclinical animal model for future translational research.
阿尔茨海默病导致的神经退行性病变引起的精神病症状，早在 Alois Alzheimer 描述首例该病病例时就已被其本人识别和记录。四分之一个多世纪前，在尝试开发疾病进展的预后标志物的背景下，精神病被确定为认知能力下降更快的独立预测因素。这一发现随后得到了很好的复制，使得精神病症状成为临床病史采集的一个重要探索领域——超越了治疗的必要性——因为它们的存在具有预后意义。此外，现在有大量研究表明，阿尔茨海默病伴精神病（AD+P）是一种遗传性疾病亚型，具有神经病理学特异性和定位性。现在人们希望，该综合征的神经生物学阐明将为转化研究铺平道路，最终产生新的治疗方法。然而，迄今为止，用于缓解 AD+P 患者痛苦的主要治疗方法是非典型抗精神病药物。这些药物已获得美国食品和药物管理局批准用于治疗精神分裂症，但它们在治疗 AD+P 方面只有轻微疗效，并且与令人困扰的发病率和死亡率相关。为了优化 AD+P 的临床方法，必须将该综合征与其他原发性精神病区分开来，并将最近的科学进展转化为针对特定疾病的治疗干预措施。在这里，我们回顾了非典型抗精神病药物在 AD+P 中的疗效，然后概述了指向额部、tau 介导的疾病模型的关键神经生物学观察结果，并提出了一种新的用于未来转化研究的临床前动物模型。
