Geriatric Unit & Gerontology-Geriatrics Research Laboratory, Department of Medical Sciences, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy.
Ageing Res Rev. 2012 Jan;11(1):87-103. doi: 10.1016/j.arr.2011.06.005. Epub 2011 Jul 7.
Neuropsychiatric symptoms (NPS) in dementia, previously denominated as behavioural and psychological symptoms of dementia, are often more distressing, impairing, and costly than cognitive symptoms, representing a major health burden for older adults. These symptoms are common features of Alzheimer's disease (AD), and are one of the major risk factors for institutionalization. There is a high prevalence of neuropsychiatric disturbances in patients with AD, including depression, anxiety, apathy, psychosis, aggression, and agitation. At present, the role of the apolipoprotein E (APOE) genotypes in the development of NPS or neuropsychiatric syndromes/endophenotypes in AD patients is unclear. In this article, we summarized the findings of the studies of NPS and neuropsychiatric syndromes in AD in relation to APOE genotypes, with special attention to the possible underlying mechanisms. While some studies failed to find a significant association between the APOE polymorphism and NPS in late-onset AD, other studies reported a significant association between the APOE ɛ4 allele and an increase in agitation/aggression, hallucinations, delusions, and late-life depression or anxiety. However, current cumulative evidence coming from the few existing longitudinal studies shows no association of APOE genotypes with NPS as a whole in AD. Some negative studies that focused on the distribution of APOE genotypes between AD patients with or without NPS further emphasized the importance of sub-grouping NPS in distinct neuropsychiatric syndromes. Explanations for the variable findings in the existing studies included differences in patient populations, differences in the assessment of neuropsychiatric symptomatology, possible lack of statistical power to detect associations in the negative studies, and small sample sizes generating false positives that cannot be consistently replicated. Finally, many reviewed studies were cross-sectional, whereas it would be of paramount importance to evaluate the risk for incident NPS in relation to the APOE genotype in prospectively followed cohorts of AD patients. In fact, identifying predisposing genetic risk factors may allow us to understand the pathophysiological features of neuropsychiatric syndromes or symptoms in AD, so optimizing possible therapeutic options.
神经精神症状（NPS）在痴呆症中，以前称为痴呆的行为和心理症状，通常比认知症状更令人痛苦、更具损伤性和更昂贵，这对老年人来说是一个主要的健康负担。这些症状是阿尔茨海默病（AD）的常见特征，也是导致住院的主要危险因素之一。AD 患者中神经精神障碍的患病率很高，包括抑郁、焦虑、淡漠、精神病、攻击和激越。目前，载脂蛋白 E（APOE）基因型在 NPS 或 AD 患者神经精神综合征/表型的发展中的作用尚不清楚。在本文中，我们总结了与 APOE 基因型相关的 AD 患者 NPS 和神经精神综合征研究的结果，特别关注潜在的机制。虽然一些研究未能发现晚发性 AD 中 APOE 多态性与 NPS 之间存在显著关联，但其他研究报告称，APOE ε4 等位基因与激越/攻击、幻觉、妄想和晚年抑郁或焦虑的增加之间存在显著关联。然而，目前来自少数现有纵向研究的累积证据表明，APOE 基因型与 AD 中的 NPS 整体没有关联。一些关注 AD 患者中有无 NPS 患者的 APOE 基因型分布的阴性研究进一步强调了将 NPS 分为不同神经精神综合征的重要性。现有研究中可变发现的解释包括患者人群的差异、神经精神症状评估的差异、可能缺乏检测关联的统计能力、以及产生无法一致复制的假阳性的小样本量。最后，许多综述研究是横断面的，而在 AD 患者的前瞻性随访队列中评估与 APOE 基因型相关的新发 NPS 的风险将至关重要。事实上，确定易患遗传风险因素可以帮助我们了解 AD 中神经精神综合征或症状的病理生理特征，从而优化可能的治疗选择。
