Professor of Psychiatry and Neurology, Director Brain Aging and Mental Health, Department of Psychiatry, New York State Psychiatric Institute and Columbia University Irving Medical Center, USA.
Curr Opin Neurol. 2023 Oct 1;36(5):498-503. doi: 10.1097/WCO.0000000000001199. Epub 2023 Aug 7.
The purpose is to review the results and clinical implications of recent studies of neuropathology in relation to neuropsychiatric symptoms (NPS) in Alzheimer's disease and related dementias, and discuss new therapeutic approaches based on evidence from clinical trials.
In a large autopsy series from a national consortium, multiple neuropathologies of dementia subtypes were common and increased severity of specific NPS during life was associated with greater severity of neuropathology across diagnoses. Based on three clinical trials, brexpiprazole, which is an antipsychotic with dopamine and serotonin receptor partial agonism properties, was recently approved for the treatment of agitation in Alzheimer's dementia by the U.S. Food and Drug Administration (FDA). Its therapeutic profile indicates modest efficacy with high safety. Brexpiprazole has not been compared to other antipsychotics that are commonly prescribed to treat agitation in dementia, though none of them have been approved for this indication. Other drugs that showed positive results in Phase 2 trials are being tested in Phase 3 trials. These include cannabinoids and drug combinations that inhibit dextromethorphan metabolism peripherally, thereby increasing its bioavailability in the brain. Apathy is common in several types of dementia, and there is initial evidence that treatment with methylphenidate, a psychostimulant, may be efficacious with good tolerability.
Greater understanding of the associations between NPS and dementia subtypes can improve clinical management of these disorders. In addition to the approval of brexpiprazole to treat agitation in Alzheimer's dementia, there is optimism about other medications based on ongoing clinical trials. Along with short-term improvement, altering the adverse impact on NPS on long-term prognosis remains an important challenge for the field.
目的是回顾近期有关阿尔茨海默病和相关痴呆症神经病理学与神经精神症状（NPS）的研究结果和临床意义，并根据临床试验证据讨论新的治疗方法。
在一个来自国家联盟的大型尸检系列中，多种痴呆亚型的神经病理学是常见的，并且在生活中特定 NPS 的严重程度增加与跨诊断的神经病理学严重程度增加相关。基于三项临床试验，brexpiprazole 是一种具有多巴胺和血清素受体部分激动特性的抗精神病药，最近被美国食品和药物管理局（FDA）批准用于治疗阿尔茨海默病痴呆症的激越。其治疗谱表明安全性高、疗效中等。尽管没有将 brexpiprazole 与其他常用于治疗痴呆激越的抗精神病药进行比较，但这些药物均未获得该适应证的批准。其他在 2 期试验中显示阳性结果的药物正在进行 3 期试验。这些药物包括大麻素和抑制去甲右吗喃在周围代谢的药物组合，从而增加其在大脑中的生物利用度。几种类型的痴呆症都很常见，并且有初步证据表明，使用哌醋甲酯（一种精神兴奋剂）治疗可能有效且耐受性良好。
更好地理解 NPS 与痴呆亚型之间的关联可以改善这些疾病的临床管理。除了批准 brexpiprazole 用于治疗阿尔茨海默病痴呆症的激越，基于正在进行的临床试验，人们对其他药物也持乐观态度。除了短期改善外，改变对 NPS 的不良影响对长期预后仍然是该领域的一个重要挑战。
