Neuropsychiatric symptoms

神经精神症状
  • 文章类型: Journal Article
    痴呆症的神经精神症状(NPS)可以通过听音乐来减轻。关于家庭收听的报道很少,编译过程,或包括生物卫生学数据的个体反应。我们的目标是从两个以家庭为基础的案例研究中提供新的见解,这些案例研究侧重于特定的音乐选择。参与者是一项更大研究的一部分,共同设计一个自动收音机,用于NPS管理的日记提醒和个人播放列表系统。播放列表被编译,这将有最大的机会实现这一目标,基于参与者的自传,叙事,心率(HR)和视频反应。参与者对音乐的反应与他们选择的流派一致-随着节奏音乐跳舞,与贝多芬的微妙反应形成对比。反复倾听可能有助于建立反应的一致性,并留出时间来传达他们的真实偏好。不是其他人建议的。如果所有这些数据收敛,然后他们可以帮助确认音乐是否适合NPS管理。
    Neuropsychiatric symptoms (NPS) in dementia can be reduced through music listening. Little has been reported on home-based listening, compilation processes, or individual responses that include biophysiological data. We aim to provide new insights from two home-based case studies focused on specific music selections. Participants were part of a larger study, co-designing an automated radio, diary reminder and personal playlist system for NPS management. Playlists were compiled that would have the best possible chance of achieving this, based on participants\' autobiographical, narrative, heart rate (HR) and videoed responses. Participant\'s responses to their music aligned with the genre they chose - dancing to up-beat music, contrasting with subtle responses to Beethoven. Repeated listens may help to establish consistency of responses and allow time to communicate their genuine preferences, not those others suggested. If all of these data converge, then they could help confirm the suitability of music for NPS management.
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  • 文章类型: Journal Article
    背景:痴呆(BPSD)的行为和心理症状是动态现象,具有高度的个体差异。我们应用了多层次框架来识别代表BPSD临床相关概况的子综合征(人与人之间的因素),并识别代表上下文驱动的日常症状经历的症状簇(人与人之间的因素)。
    方法:本研究采用纵向强化设计,招募68名痴呆症患者共同居住的家庭护理人员,以代理报告其护理接受者连续8天23种不同BPSD的日常症状经历(n=443日记)。使用多级探索性/验证性因素分析来解释嵌套数据,并将人内差异与水平间因素估计分开。
    结果:探索性因素分析根据拟合统计和临床可解释性确定了4-3-内因素结构。
    结论:本研究通过引入亚综合征和症状群的两个相关但不同的概念,为阿尔茨海默病和相关痴呆中BPSD的管理提供了重大的方法学和概念上的进步。
    结论:因为痴呆的行为和心理症状(BPSD)是动态的时间现象,当尝试创建子校正子时,这会将测量误差引入聚合组级别的估计中。我们提出了一个多层次的分析,以提供一个更有效和可靠的估计,通过分离出方差由于人内的日常波动。使用具有密集纵向数据的多层次探索性因子分析,我们确定了不同和有意义的BPSD组。人与人之间水平的四个因素代表了基于阿尔茨海默病(AD)患者之间BPSD如何共同发生的亚综合征。这些亚综合征具有临床相关性,因为它们具有已建立的临床现象的特征,并且可能具有相似的神经生物学病因。我们还发现了三个代表不同症状簇的人内因素。它们基于BPSD在给定的一天中对于患有AD和相关痴呆症的个体如何聚集在一起。这些集群可以具有共享的环境触发器。
    BACKGROUND: Behavioral and psychological symptoms in dementia (BPSD) are dynamic phenomena with a high amount of intraindividual variability. We applied a multilevel framework to identify subsyndromes (between-person factors) that represent clinically relevant profiles of BPSD and identify symptom clusters (within-person factors) that represent contextually driven daily symptom experiences.
    METHODS: This study used an intensive longitudinal design in which 68 co-residing family caregivers to persons living with dementia were recruited to proxy report on their care recipient\'s daily symptom experiences of 23 different BPSD for eight consecutive days (n = 443 diaries). A multilevel exploratory/confirmatory factor analysis was used to account for nested data and separate within-person variances from between-level factor estimates.
    RESULTS: Exploratory factor analysis identified a 4-between 3-within factor structure based on fit statistics and clinical interpretability.
    CONCLUSIONS: This study offers major methodological and conceptual advancements for management of BPSD within Alzheimer\'s disease and related dementias by introducing two related but distinct concepts of subsyndromes and symptom clusters.
    CONCLUSIONS: Because behavioral and psychological symptoms of dementia (BPSD) are dynamic temporal phenomenon, this introduces measurement error into aggregate group-level estimates when trying to create subsyndromes. We propose a multilevel analysis to provide a more valid and reliable estimation by separating out variance due to within-person daily fluctuations. Using a multilevel exploratory factor analysis with intensive longitudinal data, we identified distinct and meaningful groups of BPSD. The four factors at the between-person level represented subsyndromes that are based on how BPSD co-occurred among persons with Alzheimer\'s disease (AD). These subsyndromes are clinically relevant because they share features of established clinical phenomena and may have similar neurobiological etiologies. We also found three within-person factors representing distinct symptom clusters. They are based on how BPSD clustered together on a given day for an individual with AD and related dementias. These clusters may have shared environmental triggers.
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  • 文章类型: Editorial
    暂无摘要。
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  • 文章类型: Journal Article
    背景:照顾阿尔茨海默病和相关痴呆症患者的一个共同挑战是管理痴呆症(BPSD)的行为和心理症状。有效管理BPSD将提高痴呆症患者的生活质量,减轻护理人员的负担,降低医疗成本。
    目的:在这篇综述中,我们寻求(1)研究与光有关的室内环境质量参数,噪音,温度,和湿度与BPSD相关,以及如何控制这些参数可以帮助管理这些症状和(2)确定该领域的当前知识状态,目前的研究空白,和潜在的未来方向。
    方法:在CINAHL中进行了搜索,Embase,MEDLINE,和PsycINFO数据库,用于2007年1月至2024年2月发表的论文。我们搜索了研究与光有关的室内环境质量参数之间的关系的研究,噪音,温度,湿度和BPSD。
    结果:在2020年10月的原始搜索中总共确定了3123篇论文。经过另外2次搜索和筛选,纳入了5476篇论文中的38篇(0.69%)。在包括的论文中,光是研究最多的环境因素(34/38,89%),而研究其他环境因素与BPSD之间关系的研究较少(从5/38,13%到11/38,29%)。在38项研究中,8(21%)检测了多个室内环境质量参数。在38项研究中,有6项(16%)是环境评估的唯一来源。关于躁动和光疗之间关系的发现是矛盾的,而研究BPSD与温度或湿度之间关系的研究都是观察性的。结果表明,当环境因素被认为对痴呆症患者刺激过度或刺激不足时,行为症状往往会加剧。
    结论:这项范围审查的结果可能会为长期护理单位和老年人住房的设计提供信息,以支持就地老龄化。还需要更多的研究来更好地了解室内环境质量参数与BPSD之间的关系,并且需要对室内环境质量参数和行为症状进行更客观的测量。未来的一个方向是在实时评估中纳入客观感知和先进的计算方法,以启动及时的环境干预措施。更好地管理BPSD将使患者受益,看护者,和医疗保健系统。
    BACKGROUND: A common challenge for individuals caring for people with Alzheimer disease and related dementias is managing the behavioral and psychological symptoms of dementia (BPSD). Effective management of BPSD will increase the quality of life of people living with dementia, lessen caregivers\' burden, and lower health care cost.
    OBJECTIVE: In this review, we seek to (1) examine how indoor environmental quality parameters pertaining to light, noise, temperature, and humidity are associated with BPSD and how controlling these parameters can help manage these symptoms and (2) identify the current state of knowledge in this area, current gaps in the research, and potential future directions.
    METHODS: Searches were conducted in the CINAHL, Embase, MEDLINE, and PsycINFO databases for papers published from January 2007 to February 2024. We searched for studies examining the relationship between indoor environmental quality parameters pertaining to light, noise, temperature, and humidity and BPSD.
    RESULTS: A total of 3123 papers were identified in the original search in October 2020. After an additional 2 searches and screening, 38 (0.69%) of the 5476 papers were included. Among the included papers, light was the most studied environmental factor (34/38, 89%), while there were fewer studies (from 5/38, 13% to 11/38, 29%) examining the relationships between other environmental factors and BPSD. Of the 38 studies, 8 (21%) examined multiple indoor environmental quality parameters. Subjective data were the only source of environmental assessments in 6 (16%) of the 38 studies. The findings regarding the relationship between agitation and light therapy are conflicted, while the studies that examined the relationship between BPSD and temperature or humidity are all observational. The results suggest that when the environmental factors are deemed overstimulating or understimulating for an individual with dementia, the behavioral symptoms tend to be exacerbated.
    CONCLUSIONS: The findings of this scoping review may inform the design of long-term care units and older adult housing to support aging in place. More research is still needed to better understand the relationship between indoor environmental quality parameters and BPSD, and there is a need for more objective measurements of both the indoor environmental quality parameters and behavioral symptoms. One future direction is to incorporate objective sensing and advanced computational methods in real-time assessments to initiate just-in-time environmental interventions. Better management of BPSD will benefit patients, caregivers, and the health care system.
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  • 文章类型: Journal Article
    抑郁症及其成分显着影响痴呆的预测和严重程度,需要可靠的客观量化措施。
    我们调查了基于情绪的语音测量(效价,唤醒,和优势)在从老年抑郁量表(GDS,烦躁不安,退缩-冷漠-活力(WAV),焦虑,绝望,和主观记忆抱怨)。
    较高的WAV与更多的负效价相关(估计值=-0.133,p=0.030)。虽然载脂蛋白E(APOE)4状态与抑郁维度对情绪效价的相互作用没有达到显著性,在具有至少一个APOE4等位基因的患者中,存在更负效价和更高烦躁不安的趋势(估计值=-0.404,p=0.0846).无论痴呆的严重程度如何,关联都是相似的。
    我们的研究强调了语音生物标志物在表征抑郁维度方面的潜在效用。在未来的研究中,使用情绪刺激可能会增强情绪刺激。APOE在语音标记和抑郁维度相互作用中的作用值得在更大的样本量下进一步探索。
    报告更冷漠的参与者使用更多的负面词来描述中性图片。那些烦躁不安且至少有一个APOE4等位基因的人也倾向于使用更多的否定词。我们的结果表明,语音生物标志物在表征抑郁维度中的潜在用途。
    UNASSIGNED: Depression and its components significantly impact dementia prediction and severity, necessitating reliable objective measures for quantification.
    UNASSIGNED: We investigated associations between emotion-based speech measures (valence, arousal, and dominance) during picture descriptions and depression dimensions derived from the geriatric depression scale (GDS, dysphoria, withdrawal-apathy-vigor (WAV), anxiety, hopelessness, and subjective memory complaint).
    UNASSIGNED: Higher WAV was associated with more negative valence (estimate = -0.133, p = 0.030). While interactions of apolipoprotein E (APOE) 4 status with depression dimensions on emotional valence did not reach significance, there was a trend for more negative valence with higher dysphoria in those with at least one APOE4 allele (estimate = -0.404, p = 0.0846). Associations were similar irrespective of dementia severity.
    UNASSIGNED: Our study underscores the potential utility of speech biomarkers in characterizing depression dimensions. In future research, using emotionally charged stimuli may enhance emotional measure elicitation. The role of APOE on the interaction of speech markers and depression dimensions warrants further exploration with greater sample sizes.
    UNASSIGNED: Participants reporting higher apathy used more negative words to describe a neutral picture.Those with higher dysphoria and at least one APOE4 allele also tended to use more negative words.Our results suggest the potential use of speech biomarkers in characterizing depression dimensions.
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  • 文章类型: Journal Article
    神经精神症状(NPS)和情绪障碍在患有轻度认知障碍(MCI)的个体中很常见,并增加进展为痴呆的风险。可穿戴设备收集生理和行为数据可以帮助远程,被动,以及对情绪和NPS的持续监测,克服现有评估方法的局限性和不便。在这项纵向研究中,我们基于来自腕部穿戴设备的传感器数据检测了数字生物标志物的预测能力,以确定患有主要MCI的老年人每日NPS和情绪障碍的严重程度.除了常规的生理生物标志物,如心率变异性和皮肤电导水平,我们利用自监督卷积自动编码器从生理数据中提取的深度学习特征。结合常见数字生物标志物和深层特征的模型预测抑郁症严重程度评分,平均相关系数为r=0.73。研究人群中情绪障碍症状的总严重程度r=0.67,轻度行为障碍评分r=0.69.我们的研究结果表明,从可穿戴设备和深度学习方法中收集的生理生物标志物有可能用于对老年人的心理健康症状进行连续且不引人注意的评估。包括那些有MCI的.试验注册:该试验于2021年9月28日在ClinicalTrials.gov(NCT05059353)注册,标题为“基于数字的多领域干预对轻度认知障碍的有效性和安全性”。
    Neuropsychiatric symptoms (NPS) and mood disorders are common in individuals with mild cognitive impairment (MCI) and increase the risk of progression to dementia. Wearable devices collecting physiological and behavioral data can help in remote, passive, and continuous monitoring of moods and NPS, overcoming limitations and inconveniences of current assessment methods. In this longitudinal study, we examined the predictive ability of digital biomarkers based on sensor data from a wrist-worn wearable to determine the severity of NPS and mood disorders on a daily basis in older adults with predominant MCI. In addition to conventional physiological biomarkers, such as heart rate variability and skin conductance levels, we leveraged deep-learning features derived from physiological data using a self-supervised convolutional autoencoder. Models combining common digital biomarkers and deep features predicted depression severity scores with a correlation of r = 0.73 on average, total severity of mood disorder symptoms with r = 0.67, and mild behavioral impairment scores with r = 0.69 in the study population. Our findings demonstrated the potential of physiological biomarkers collected from wearables and deep learning methods to be used for the continuous and unobtrusive assessments of mental health symptoms in older adults, including those with MCI. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (NCT05059353) on September 28, 2021, titled \"Effectiveness and Safety of a Digitally Based Multidomain Intervention for Mild Cognitive Impairment\".
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  • 文章类型: Journal Article
    目的:本研究评估了大剂量维生素D补充剂在减轻COVID后综合征患者疲劳和神经精神症状方面的有效性。
    方法:在8周内,双盲,随机化,安慰剂对照试验,纳入80例COVID后疲劳或神经精神症状患者。参与者被随机分配每周接受60,000IU维生素D(n=40)或安慰剂(n=40),为期8周。使用11项Chalder疲劳量表(CFQ-11)评估临床结果;21项抑郁症,焦虑,和压力量表(DASS-21);匹兹堡睡眠质量指数(PSQI);Addenbrooke的认知检查III(ACE);以及跟踪测试A和B(TMT-A和TMT-B)。炎症标志物的基线和8周测量,包括白细胞介素6(IL-6)和C反应蛋白(CRP),也被收集了。
    结果:发现维生素D组对CFQ的显着改善(系数-3.5,P=0.024),DASS焦虑(-2.0,P=0.011),和ACE(2.1,P=0.012)。在PSQI中没有观察到显著差异,DASS-抑郁,TMT,IL-6或CRP水平。两组之间的不良事件发生率相当,未报告严重不良事件。
    结论:大剂量补充维生素D可能通过减轻疲劳使COVID后综合征患者受益,缓解焦虑,改善认知症状,副作用最小。
    OBJECTIVE: This study evaluated the effectiveness of high-dose vitamin D supplementation in alleviating fatigue and neuropsychiatric symptoms in post-COVID syndrome.
    METHODS: In an 8-week, double-blind, randomized, placebo-controlled trial, 80 patients with post-COVID fatigue or neuropsychiatric symptoms were enrolled. Participants were randomly assigned to receive either 60,000 IU of vitamin D weekly (n = 40) or a placebo (n = 40) for 8 weeks. Clinical outcomes were assessed using the 11-item Chalder Fatigue Scale (CFQ-11); 21-item Depression, Anxiety, and Stress Scale (DASS-21); Pittsburgh Sleep Quality Index (PSQI); Addenbrooke\'s Cognitive Examination III (ACE); and Trail Making Test A and B (TMT-A and TMT-B). Baseline and 8-week measurements of inflammatory markers, including interleukin 6 (IL-6) and C-reactive protein (CRP), were also collected.
    RESULTS: Significant improvements were found in the vitamin D group for CFQ (coefficient -3.5, P = 0.024), DASS-anxiety (-2.0, P = 0.011), and ACE (2.1, P = 0.012). No significant differences were observed in PSQI, DASS-depression, TMT, IL-6, or CRP levels. The incidence of adverse events was comparable between groups, with no serious adverse events reported.
    CONCLUSIONS: High-dose vitamin D supplementation may benefit patients with post-COVID syndrome by reducing fatigue, alleviating anxiety, and improving cognitive symptoms, with minimal side effects.
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  • 文章类型: Journal Article
    背景:神经精神症状(NPS)在老年人中很常见,可能发生在痴呆症发展的早期,并与更快的认知能力下降有关。这里,我们的目的是调查血浆神经丝轻链(NfL)水平,胶质纤维酸性蛋白(GFAP),在苏氨酸181(pTau181)磷酸化的tau与当前NPS相关,并预测非痴呆老年人的未来NPS。此外,我们测试了NPS与血浆生物标志物的结合是否有助于预测阿尔茨海默病(AD)病理和认知功能减退.
    方法:在记忆中心的一项纵向脑老化研究中,对151名认知正常(n=76)或轻度认知障碍(n=75)的参与者进行了检查,洛桑大学医院,瑞士。NfL的血浆水平,GFAP,在基线时测量pTau181以及AD病理的CSF生物标志物。NPS通过神经精神调查问卷(NPI-Q)进行评估,以及基线和随访时的认知和功能表现(平均:20个月)。使用不同的回归和ROC分析来解决感兴趣的关联。
    结果:三种血浆生物标志物均不与基线时的NPS相关。较高的GFAP水平与随访时NPS的存在相关(OR=2.8,p=0.002),随着时间的推移,NfL和GFAP越高,NPI-Q严重程度评分越高(分别为β=0.25,p=.034和β=0.30,p=.013)。将NPS和血浆生物标志物添加到参考模型中改善了对未来NPS(AUC0.72至0.88,p=.002)和AD病理学(AUC0.78至0.87,p=.010)的预测,但不是认知能力下降(AUC0.79至0.85,p=.081)。
    结论:血浆NfL和GFAP均与未来NPS和NPS严重程度改变相关。考虑到NPS的存在以及基于血液的AD生物标志物可以改善NPS随时间的临床进展的预测,并为非痴呆老年人的临床决策提供信息。
    BACKGROUND: Neuropsychiatric symptoms (NPS) are common in older people, may occur early in the development of dementia disorders, and have been associated with faster cognitive decline. Here, our objectives were to investigate whether plasma levels of neurofilament light chain (NfL), glial fibrillary acid protein (GFAP), and tau phosphorylated at threonine 181 (pTau181) are associated with current NPS and predict future NPS in non-demented older people. Furthermore, we tested whether the presence of NPS combined with plasma biomarkers are useful to predict Alzheimer\'s disease (AD) pathology and cognitive decline.
    METHODS: One hundred and fifty-one participants with normal cognition (n = 76) or mild cognitive impairment (n = 75) were examined in a longitudinal brain aging study at the Memory Centers, University Hospital of Lausanne, Switzerland. Plasma levels of NfL, GFAP, and pTau181 along with CSF biomarkers of AD pathology were measured at baseline. NPS were assessed through the Neuropsychiatric Inventory Questionnaire (NPI-Q), along with the cognitive and functional performance at baseline and follow-up (mean: 20 months). Different regression and ROC analyses were used to address the associations of interest.
    RESULTS: None of the three plasma biomarker was associated with NPS at baseline. Higher GFAP levels were associated with the presence of NPS at follow-up (OR = 2.8, p = .002) and both, higher NfL and higher GFAP with an increase in the NPI-Q severity score over time (β = 0.25, p = .034 and β = 0.30, p = .013, respectively). Adding NPS and the plasma biomarkers to a reference model improved the prediction of future NPS (AUC 0.72 to 0.88, p = .002) and AD pathology (AUC 0.78 to 0.87, p = .010), but not of cognitive decline (AUC 0.79 to 0.85, p = .081).
    CONCLUSIONS: Plasma NfL and GFAP are both associated with future NPS and NPS severity change. Considering the presence of NPS along with blood-based AD-biomarkers may improve the prediction of clinical progression of NPS over time and inform clinical decision-making in non-demented older people.
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  • 文章类型: Journal Article
    阿尔茨海默病(Alzheimer\'sdisease,AD)是一种以进行性认知功能减退为特征的常见神经退行性疾病。几乎所有AD患者都会出现神经精神症状(NPS)。躁动是最令人痛苦和具有挑战性的NPS之一。Brexpiprazole是一种口服抗精神病药物,是美国第一个被批准用于治疗与AD引起的痴呆相关的躁动的药物。其作用被认为来自其部分5-羟色胺5-HT1A和多巴胺D2受体激动剂活性和5-羟色胺5-HT2A受体拮抗作用。Brexpiprazole是一种维持药物,并且不应“根据需要”或“PRN”治疗突破性躁动。Brexiprazole是CYP2D6和CYP3A4的主要底物。药物相互作用或肾功能或肝功能受损可能需要剂量调整。临床试验发现,2至3毫克/天的布立哌唑在躁动方面显着改善,与安慰剂组相比,在第12周时,在Cohen-Mansfield躁动量表总分的变化方面,与安慰剂组相比,布立哌唑组显示出比基线高大约5分的降低.Brexpiprazole通常具有良好的耐受性和安全性,当用于这种适应症时,常见的不良反应包括头晕,头痛,失眠,鼻咽炎,嗜睡,和尿路感染.像其他用于AD患者躁动的抗精神病药一样,与安慰剂相比,布立哌唑与更高的死亡率相关.在长期护理环境中,它的使用有几个注意事项。益处包括耐受性良好的口服药剂和显示对躁动的统计学显著影响的临床数据。然而,尚未在针对其他抗精神病药的正面交锋临床试验中研究过,如果躁动评分降低转化为临床上有意义的差异,则有不同的意见。批准的布立哌唑信号有利的即将到来的药物为这一适应症,包括艾司西酞普兰和右美沙芬-安非他酮。艾司西酞普兰和右美沙芬-安非他酮目前都在进行临床试验。
    Alzheimer\'s disease (AD) is a prevalent neurodegenerative disease characterized by progressive cognitive and functional decline. Nearly all patients with AD develop neuropsychiatric symptoms (NPSs). Agitation is one of the most distressing and challenging NPS. Brexpiprazole is an oral antipsychotic and is the first approved pharmacologic agent in the United States for the treatment of agitation associated with dementia due to AD. Its effect is thought to be from its partial serotonin 5-HT1A and dopamine D2 receptor agonist activity and serotonin 5-HT2A receptor antagonism. Brexpiprazole is a maintenance medication, and it should not be used \"as needed\" or as a \"PRN\" treatment for breakthrough agitation. Brexpiprazole is a major substrate of CYP2D6 and CYP3A4. Dose adjustments may be required for drug interactions or impaired renal or hepatic function. Clinical trials found brexpiprazole 2 to 3 mg/d demonstrated significant improvements in agitation, with brexpiprazole showing an approximate 5-point greater reduction on change in the Cohen-Mansfield Agitation Inventory total score at week 12 from baseline compared with placebo. Brexpiprazole is generally well tolerated and safe, and common adverse reactions when used for this indication include dizziness, headaches, insomnia, nasopharyngitis, somnolence, and urinary tract infections. Like other antipsychotics used for agitation in AD, brexpiprazole is associated with higher mortality rates compared with placebo. In a long-term care setting, there are several considerations for its use. Benefits include an oral agent that is well tolerated and clinical data showing statistically significant effects on agitation. However, brexpiprazole has not been studied in head-to-head clinical trials against other antipsychotics, and there are differing opinions if the agitation score reductions translate to a clinically meaningful difference. The approval of brexpiprazole signals favorably for upcoming agents for this indication, including escitalopram and dextromethorphan-bupropion. Both escitalopram and dextromethorphan-bupropion are currently undergoing clinical trials.
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  • 文章类型: Journal Article
    背景:早发性阿尔茨海默病(EOAD)比晚发性阿尔茨海默病(LOAD)表现出更高的神经精神症状负担。我们旨在确定EOAD和LOAD之间神经精神症状的严重程度和蓝斑(LC)完整性的差异,以说明疾病阶段。
    方法:纳入诊断为AD的104名受试者和32名健康对照。参与者接受磁共振成像(MRI)以测量LC完整性,脑脊液(CSF)和神经精神量表(NPI)中去甲肾上腺素水平的测量。我们分析了LC-去甲肾上腺素测量值与临床和阿尔茨海默病(AD)生物标志物的关联。
    结果:EOAD显示NPI得分较高,较低的LC完整性,与负荷相比,脑脊液去甲肾上腺素水平相似。值得注意的是,EOAD表现出较低的LC完整性,与疾病分期无关。LC完整性与神经精神症状呈负相关。与AD生物标志物相关的AD中去甲肾上腺素水平升高。
    结论:LC完整性降低对神经精神症状有负面影响。与LOAD相比,EOAD中更高的LC变性可以解释EOAD中更严重的神经精神症状。
    结论:与晚发性AD相比,早发性AD(EOAD)的LC变性更大。Tau衍生的LC变性导致神经精神症状的严重程度更高。EOAD具有LC系统更深刻的选择性漏洞。LC变性与AD中脑脊液去甲肾上腺素水平的增加有关。
    BACKGROUND: Early-onset Alzheimer\'s disease (EOAD) shows a higher burden of neuropsychiatric symptoms than late-onset Alzheimer\'s disease (LOAD). We aim to determine the differences in the severity of neuropsychiatric symptoms and locus coeruleus (LC) integrity between EOAD and LOAD accounting for disease stage.
    METHODS: One hundred four subjects with AD diagnosis and 32 healthy controls were included. Participants underwent magnetic resonance imaging (MRI) to measure LC integrity, measures of noradrenaline levels in cerebrospinal fluid (CSF) and Neuropsychiatric Inventory (NPI). We analyzed LC-noradrenaline measurements and clinical and Alzheimer\'s disease (AD) biomarker associations.
    RESULTS: EOAD showed higher NPI scores, lower LC integrity, and similar levels of CSF noradrenaline compared to LOAD. Notably, EOAD exhibited lower LC integrity independently of disease stage. LC integrity negatively correlated with neuropsychiatric symptoms. Noradrenaline levels were increased in AD correlating with AD biomarkers.
    CONCLUSIONS: Decreased LC integrity negatively contributes to neuropsychiatric symptoms. The higher LC degeneration in EOAD compared to LOAD could explain the more severe neuropsychiatric symptoms in EOAD.
    CONCLUSIONS: LC degeneration is greater in early-onset AD (EOAD) compared to late-onset AD. Tau-derived LC degeneration drives a higher severity of neuropsychiatric symptoms. EOAD harbors a more profound selective vulnerability of the LC system. LC degeneration is associated with an increase of cerebrospinal fluid noradrenaline levels in AD.
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