Is bigger better? Towards a mechanistic understanding of neuropsychiatric symptoms in Alzheimer's disease.
Is bigger better? Towards a mechanistic understanding of neuropsychiatric symptoms in Alzheimer's disease.
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DOI：
10.1017/s1041610221001277
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发表时间：
2021-11
影响因子：
7
通讯作者：
Rosenberg PB
中科院分区：
文献类型：
--
作者：
Nowrangi MA;Rosenberg PB
越来越清楚的是，阿尔茨海默病（AD）的公共卫生负担不仅是由于认知能力下降，而且还由于神经精神症状（AD）。诸如激越、抑郁、焦虑和冷漠的疾病在AD中高度流行（Tschanz等人，2011年），并增加照顾者的负担，医疗保健成本和机构化的风险（Storti等人，2016年）。非药物干预被认为是AD患者的一线治疗，但并不总是使用，也不总是有效的，并且没有FDA批准的药物用于AD患者（尽管利培酮在欧洲被批准用于短期治疗激越）。目前正在研究几种药物用于AD的再利用，包括用于冷漠的哌甲酯（Rosenberg等人，2013）和选择性5-羟色胺再摄取抑制剂（Porsteinsson等人，2014）、大麻素（Outen等人，2021），以及哌唑嗪用于AD中的激动。但如果我们能针对生物机制，治疗可能会更有效。虽然我们对AD中神经元的机制的理解比我们对认知的核心AD机制的理解要早得多，但神经影像学研究提供了越来越多的线索。在几项研究中，AD中的抑郁与前扣带皮质（ACC）的体积或皮质厚度减小相关（Liu et al.，2017; Zahodne等人，2013）以及海马体积减小（Elcombe et al.，2015年; Xie等人，2013年）。冷漠与包括下颞叶皮层、后扣带皮层（PCC）和额叶结构（包括眶额皮层以及ACC）的额叶-皮层下奖赏回路的变化相关（Rosenberg等人，2015年）的报告。由于对激动患者进行成像的挑战，AD的激动本质上很难研究，但迄今为止有限的数据表明与左下额叶/脑岛和双侧压后皮质萎缩有关（Rafii等人，2014）和额缘萎缩（Trzepacz等人，2013），以及前扣带束中白色物质完整性降低（Tighe等人，2012年）。AD患者的精神病与颞叶和顶叶的萎缩有显著的相关性，而与额叶和枕叶结构以及皮质下结构的相关性较低
It is increasingly clear that the public health burden of Alzheimer’s disease (AD) is not solely due to cognitive decline but also to neuropsychiatric symptoms (NPS). NPS such as agitation, depression, anxiety, and apathy are highly prevalent in AD (Tschanz et al., 2011) and increase caregiver burden, health care costs, and risk of institutionalization (Storti et al., 2016). Nonpharmacologic interventions are considered first-line treatment for NPS in AD but are not consistently used nor always effective and there are no FDA-approved medications for NPS in AD (although risperidone is approved for short-term treatment of agitation in Europe). Several drugs are currently being studied for repurposing for NPS in AD including methylphenidate for apathy (Rosenberg et al., 2013) and selective serotonin reuptake inhibitors (Porsteinsson et al., 2014), cannabinoids (Outen et al., 2021), and prazosin for agitation in AD among others. But treatments might be more effective if we could target biological mechanisms. While our understanding of mechanisms of NPS in AD is at a much earlier stage than our understanding of core AD mechanisms of cognition, there are increasing clues from neuroimaging studies. Depression in AD has been associated with decreased volume or cortical thickness of the anterior cingulate cortex (ACC) in several studies (Liu et al., 2017; Zahodne et al., 2013) as well as decreased hippocampal volume (Elcombe et al., 2015; Xie et al., 2013). Apathy has been associated with changes to the frontal-subcortical reward circuitry including the inferior temporal cortex, posterior cingulate cortex (PCC), and frontal lobe structures including the orbitofrontal cortex as well as the ACC (Rosenberg et al., 2015). Agitation in AD is innately difficult to study due to the challenges of imaging agitated patients, but the limited data to date suggest associations with atrophy in the left inferior frontal/insula and bilateral retrosplenial cortices (Rafii et al., 2014) and with frontolimbic atrophy (Trzepacz et al., 2013), as well as decreased white matter integrity in the anterior cingulum bundle (Tighe et al., 2012). Psychosis in AD shows prominent associations with atrophy of the temporal and parietal lobes, and less so with frontal and occipital lobe structures and subcortical structures