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Evidence that Alzheimer’s Disease Is a Disease of Competitive Synaptic Plasticity Gone Awry 阿尔茨海默病是一种突触竞争性可塑性失调疾病的证据
IF 4 3区 医学 Q1 Psychology Pub Date : 2024-04-21 DOI: 10.3233/jad-240042
Zhen Huang
 Mounting evidence indicates that a physiological function of amyloid-β (Aβ) is to mediate neural activity-dependent homeostatic and competitive synaptic plasticity in the brain. I have previously summarized the lines of evidence supporting this hypothesis and highlighted the similarities between Aβ and anti-microbial peptides in mediating cell/synapse competition. In cell competition, anti-microbial peptides deploy a multitude of mechanisms to ensure both self-protection and competitor elimination. Here I review recent studies showing that similar mechanisms are at play in Aβ-mediated synapse competition and perturbations in these mechanisms underpin Alzheimer’s disease (AD). Specifically, I discuss evidence that Aβ and ApoE, two crucial players in AD, co-operate in the regulation of synapse competition. Glial ApoE promotes self-protection by increasing the production of trophic monomeric Aβ and inhibiting its assembly into toxic oligomers. Conversely, Aβ oligomers, once assembled, promote the elimination of competitor synapses via direct toxic activity and amplification of “eat-me” signals promoting the elimination of weak synapses. I further summarize evidence that neuronal ApoE may be part of a gene regulatory network that normally promotes competitive plasticity, explaining the selective vulnerability of ApoE expressing neurons in AD brains. Lastly, I discuss evidence that sleep may be key to Aβ-orchestrated plasticity, in which sleep is not only induced by Aβ but is also required for Aβ-mediated plasticity, underlining the link between sleep and AD. Together, these results strongly argue that AD is a disease of competitive synaptic plasticity gone awry, a novel perspective that may promote AD research.
越来越多的证据表明,淀粉样蛋白-β(Aβ)的生理功能是介导大脑中依赖神经活动的平衡和竞争性突触可塑性。我曾总结过支持这一假说的证据,并强调了 Aβ 与抗微生物肽在介导细胞/突触竞争方面的相似之处。在细胞竞争中,抗微生物肽采用多种机制确保自我保护和消灭竞争者。在此,我回顾了最近的研究,这些研究表明,类似的机制也在 Aβ 介导的突触竞争中发挥作用,而这些机制的紊乱是阿尔茨海默病(AD)的基础。具体而言,我将讨论 Aβ 和载脂蛋白E(ApoE)这两种在阿兹海默病(AD)中起关键作用的物质共同调节突触竞争的证据。神经胶质载脂蛋白E通过增加营养性单体Aβ的产生和抑制其组装成毒性寡聚体来促进自我保护。相反,Aβ 寡聚体一旦聚集,就会通过直接的毒性活动和 "吃我 "信号的放大促进弱突触的消除,从而促进竞争突触的消除。我进一步总结了神经元载脂蛋白E可能是通常促进竞争可塑性的基因调控网络的一部分的证据,从而解释了AD大脑中表达载脂蛋白E的神经元的选择性脆弱性。最后,我讨论了睡眠可能是Aβ协调可塑性的关键的证据,其中睡眠不仅是Aβ诱导的,也是Aβ介导的可塑性所必需的,强调了睡眠与AD之间的联系。总之,这些结果有力地证明,注意力缺失症是一种竞争性突触可塑性出错的疾病,这种新观点可能会促进注意力缺失症的研究。
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引用次数: 0
Effects of Exercise on Urinary AD7c-NTP (Alzheimer-Associated Neuronal Thread Protein) Levels and Cognitive Function Among Active Korean Elderly: A Randomized Controlled Trial 运动对活跃的韩国老年人尿液中 AD7c-NTP(阿尔茨海默氏症相关神经元线粒体蛋白)水平和认知功能的影响:随机对照试验
IF 4 3区 医学 Q1 Psychology Pub Date : 2024-04-20 DOI: 10.3233/jad-230946
Donghyun Kim, Parivash Jamrasi, Xinxing Li, Soyoung Ahn, Yunho Sung, Seohyun Ahn, Yuseon Kang, Wook Song
Background: Alzheimer-associated neuronal thread protein (AD7c-NTP) has been demonstrated to have high diagnostic accuracy in differentiating Alzheimer’s disease (AD) patients from healthy individuals. However, it is yet unclear whether exercise can lower the level of AD7c-NTP in urine among active Korean elderly. Objective: To assess the effect of exercise on AD7c-ntp levels in urine and cognitive function among active Korean elderly. Methods: In total, 40 Korean elderly (≥65 years) were divided into Active Control group (CG, n = 10), Aerobic exercise group (AG, n = 18), and combined Resistance/Aerobic exercise group (RAG, n = 12). A total of 12 weeks of exercise intervention was implemented. At week 0 and 12, cognitive performance (Korean Mini-Mental State Examination, Korean-Color Word Stroop test), grip strength, and body composition (muscle mass and body fat percentage) were measured. Also, a morning urine sample was obtained from each subject. The level of AD7c-NTP was measured using competitive enzyme-linked immunosorbent assay (ELISA). Results: After 12 weeks of exercise intervention, there was a significant difference of AD7c-NTP levels between RAG and CG (p = 0.026), AG and CG (p = 0.032), respectively. Furthermore, the AD7c-NTP levels in urine showed negative correlation with K-MMSE scores (r = –0.390, p = 0.013) and grip strength (r = –0.376, p = 0.017), among all participants after exercise intervention. Conclusions: This is the first study to investigate urine biomarker through exercise intervention. In future stuides, participants who have low cognitive function and low activity levels need to be recruited to observe more significant ‘Exercise’ effect.
背景:阿尔茨海默氏症相关神经元线粒体蛋白(AD7c-NTP)已被证明在区分阿尔茨海默氏症(AD)患者和健康人方面具有很高的诊断准确性。然而,运动是否能降低好动的韩国老年人尿液中的 AD7c-NTP 水平尚不清楚。目的评估运动对活跃的韩国老年人尿液中 AD7c-ntp 水平和认知功能的影响。方法:共选取了 40 名韩国老年人(年龄不超过 50 岁)作为研究对象:将 40 名韩国老年人(≥65 岁)分为活动对照组(CG,n = 10)、有氧运动组(AG,n = 18)和阻力/有氧运动联合组(RAG,n = 12)。运动干预共进行了 12 周。在第 0 周和第 12 周,测量了认知能力(韩国迷你精神状态检查、韩国颜色词 Stroop 测试)、握力和身体成分(肌肉质量和体脂百分比)。此外,还采集了每位受试者的晨尿样本。采用竞争性酶联免疫吸附试验(ELISA)测量 AD7c-NTP 的水平。结果显示运动干预 12 周后,RAG 和 CG(P = 0.026)、AG 和 CG(P = 0.032)的 AD7c-NTP 水平分别存在显著差异。此外,运动干预后,所有参与者尿液中的 AD7c-NTP 水平与 K-MMSE 评分(r = -0.390,p = 0.013)和握力(r = -0.376,p = 0.017)呈负相关。结论这是第一项通过运动干预研究尿液生物标志物的研究。在今后的研究中,需要招募认知功能低下和活动水平低的参与者,以观察更显著的 "运动 "效果。
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引用次数: 0
Gene Association Study of the Urokinase Plasminogen Activator and Its Receptor Gene in Alzheimer’s Disease 阿尔茨海默病中尿激酶原酶原激活剂及其受体基因的基因关联研究
IF 4 3区 医学 Q1 Psychology Pub Date : 2024-04-20 DOI: 10.3233/jad-231383
Ozde Cetinsoy, Ijeoma Anyanwu, Harikrishnan Krishnanand, Gokulakrishnan Natarajan, Naveen Ramachandran, Alan Thomas, Keeley J. Brookes
Background: The role of the innate immune system has long been associated with Alzheimer’s disease (AD). There is now accumulating evidence that the soluble Urokinase Plasminogen Activator Receptor pathway, and its genes, PLAU and PLAUR may be important in AD, and yet there have been few genetic association studies to explore this. Objective: This study utilizes the DNA bank of the Brains for Dementia Research cohort to investigate the genetic association of common polymorphisms across the PLAU and PLAUR genes with AD. Methods: TaqMan genotyping assays were used with standard procedures followed by association analysis in PLINK. Results: No association was observed between the PLAU gene and AD; however, two SNPs located in the PLAUR gene were indicative of a trend towards association but did not surpass multiple testing significance thresholds. Conclusions: Further genotyping studies and exploration of the consequences of these SNPs on gene expression and alternative splicing are warranted to fully uncover the role this system may have in AD.
背景:长期以来,先天性免疫系统的作用一直与阿尔茨海默病(AD)有关。目前有越来越多的证据表明,可溶性尿激酶原激活剂受体通路及其基因 PLAU 和 PLAUR 可能对阿兹海默症有重要影响,但很少有遗传关联研究对此进行探讨。研究目的本研究利用脑痴呆研究队列的 DNA 库,调查 PLAU 和 PLAUR 基因的常见多态性与 AD 的遗传关联。研究方法采用标准程序进行 TaqMan 基因分型检测,然后在 PLINK 中进行关联分析。结果未观察到 PLAU 基因与 AD 之间存在关联;然而,位于 PLAUR 基因的两个 SNPs 显示出关联趋势,但未超过多重检验显著性阈值。结论有必要进一步开展基因分型研究,并探索这些 SNP 对基因表达和替代剪接的影响,以全面揭示该系统在 AD 中可能扮演的角色。
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引用次数: 0
Exploring Psychosis in Neurodegenerative Dementia: Connecting Symptoms to Neurobiology 探索神经退行性痴呆症中的精神病:将症状与神经生物学联系起来
IF 4 3区 医学 Q1 Psychology Pub Date : 2024-04-20 DOI: 10.3233/jad-240328
Christopher B. Morrow, G. Pontone
The following commentary discusses a review by Cressot et al. entitled: ‘Psychosis in Neurodegenerative Dementias: A Systematic Comparative Review’. The authors describe the epidemiology and phenomenology of psychosis across neurodegenerative dementias. Dementia with Lewy bodies had the highest reported prevalence of psychosis at 74% followed by Alzheimer’s disease, 54% and frontotemporal degeneration, 42% . Detailed characterization of psychosis shows differences in the types of hallucinations and delusions by dementia type. These findings suggest that different types of dementia related pathology are associated with high rates of psychosis with more specific symptom profiles than previously appreciated. Understanding the differences and variety of psychotic experiences across dementia types may have diagnostic and therapeutic implications for treating hallucinations and delusions in populations suffering from neurodegenerative diseases.
以下评论讨论了 Cressot 等人撰写的题为 "神经退行性痴呆症中的精神病 "的综述:系统性比较综述》。作者描述了神经退行性痴呆症中精神病的流行病学和现象学。据报道,路易体痴呆症的精神病发病率最高,为 74%,其次是阿尔茨海默病(54%)和额颞变性(42%)。精神病的详细特征显示,不同痴呆症类型的幻觉和妄想类型也有所不同。这些研究结果表明,与痴呆症相关的不同病理类型与精神病的高发病率有关,其症状特征比以前所了解的更为具体。了解不同痴呆类型的精神病体验的差异和多样性,可能会对治疗神经退行性疾病患者的幻觉和妄想产生诊断和治疗意义。
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引用次数: 0
Associations of Handgrip Strength Weakness and Asymmetry with Lower Cognitive Function: Results from the National Health and Nutrition Examination Survey (2011–2014) 手握力弱和不对称与认知功能低下的关系:国家健康与营养调查(2011-2014 年)的结果
IF 4 3区 医学 Q1 Psychology Pub Date : 2024-04-19 DOI: 10.3233/jad-231375
Lang Peng, Qingwei Xiang, Yong Zhou, Renyi Yin
Background: The joint associations of handgrip strength (HGS) weakness and asymmetry with cognitive decline remain understudied in older adults. Objective: To investigate the associations between HGS weakness, asymmetry, and lower cognitive function in a nationally representative sample of older Americans. Methods: This cross-sectional study utilized data from the National Health and Nutrition Examination Survey 2011–2014. Weakness was defined as HGS <26 kg for men and <16 kg for women. Asymmetry was determined by calculating the ratio of dominant to non-dominant HGS. Participants with an HGS ratio <0.90 or >1.10 were classified as having any HGS asymmetry. Those with an HGS ratio >1.10 exhibited dominant HGS asymmetry, while those with an HGS ratio <0.90 displayed nondominant HGS asymmetry, respectively. Lower cognitive functioning was defined as global cognitive composite scores more than 1 standard deviation below the mean. Covariate-adjusted logistic regression models were used to analyze the associations between HGS asymmetry/weakness and lower cognitive functioning. Results: Compared to individuals with non-weak and symmetric HGS, those with any HGS asymmetry alone and weakness alone had 1.017 (95% confidence interval [CI]: 0.707–1.463) and 1.391 (95% CI: 0.542–3.571) greater odds for cognitive decline, while co-occurrence of both HGS asymmetry and weakness was associated with 3.724 (95% CI: 1.711–8.107) greater odds for lower cognitive function after controlling for confounders. Cnclusions: Individuals exhibiting both diminished and asymmetrical HGS demonstrated an elevated susceptibility to cognitive impairment, thereby implying that the inclusion of HGS asymmetry assessment in conjunction with weakness evaluation may enhance the accuracy of prognosticating cognitive decline.
背景:在老年人中,手握力(HGS)薄弱和不对称与认知能力下降之间的关系仍未得到充分研究。目的: 研究手握力弱、不对称和认知能力下降之间的关系:在具有全国代表性的美国老年人样本中调查手握力弱、不对称与认知功能下降之间的关系。方法: 采用横断面研究方法:这项横断面研究利用了 2011-2014 年全国健康与营养调查的数据。HGS比率为1.10的人被归类为HGS不对称。HGS 比率大于 1.10 的人表现为优势 HGS 不对称,而 HGS 比率小于 0.90 的人则表现为非优势 HGS 不对称。认知功能低下的定义是全球认知综合评分低于平均值 1 个标准差以上。采用协变量调整的逻辑回归模型分析 HGS 不对称/弱与认知功能低下之间的关联。结果显示与HGS不对称和对称的个体相比,单独存在HGS不对称和单独存在HGS虚弱的个体出现认知功能下降的几率分别为1.017(95% 置信区间[CI]:0.707-1.463)和1.391(95% CI:0.542-3.571),而同时存在HGS不对称和虚弱的个体出现认知功能下降的几率为3.724(95% CI:1.711-8.107)。结论:同时表现出HGS减弱和不对称的个体对认知功能损害的易感性更高,这意味着将HGS不对称评估与虚弱评估结合起来可能会提高认知功能衰退预后的准确性。
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引用次数: 0
Impaired Glymphatic Flow on Diffusion Tensor MRI as a Marker of Neurodegeneration in Alzheimer’s Disease: Correlation with Gray Matter Volume Loss and Cognitive Decline Independent of Cerebral Amyloid Deposition 弥散张量磁共振成像(Diffusion Tensor MRI)上的淋巴流动受损是阿尔茨海默病神经退行性变的标志:与脑淀粉沉积无关的灰质体积损失和认知能力下降的相关性
IF 4 3区 医学 Q1 Psychology Pub Date : 2024-04-19 DOI: 10.3233/jad-231131
Minjae Kim, Yoo Sung Song, Kyunghwa Han, Yun Jung Bae, Ji Won Han, Ki Woong Kim
Background: Impaired glymphatic flow on the Alzheimer’s disease (AD) spectrum may be evaluated using diffusion tensor image analysis along the perivascular space (DTI-ALPS). Objective: We aimed to validate impaired glymphatic flow and explore its association with gray matter volume, cognitive status, and cerebral amyloid deposition on the AD spectrum. Methods: 80 participants (mean age, 76.9±8.5 years; 57 women) with AD (n = 65) and cognitively normal (CN) (n = 15) who underwent 3T brain MRI including DTI and/or amyloid PET were included. After adjusting for age, sex, apolipoprotein E status, and burden of white matter hyperintensities, the ALPS-index was compared according to the AD spectrum. The association between the ALPS-index and gray matter volume, cognitive status, and quantitative amyloid from PET was assessed. Results: The ALPS-index in the AD was significantly lower (mean, 1.476; 95% CI, 1.395–1.556) than in the CN (1.784;1.615–1.952; p = 0.026). Volumes of the entorhinal cortex, hippocampus, temporal pole, and primary motor cortex showed significant associations with the ALPS-index (all, p <  0.05). There was a positive correlation between the ALPS-index and MMSE score (partial r = 0.435; p <  0.001), but there was no significant correlation between the ALPS-index and amyloid SUVRs (all, p >  0.05). Conclusions: Decreased glymphatic flow measured by DTI-ALPS in AD may serve as a marker of neurodegeneration correlating with structural atrophy and cognitive decline.
背景:阿尔茨海默病(AD)的血流受损情况可通过沿血管周围空间的弥散张量图像分析(DTI-ALPS)进行评估。我们的目标是我们旨在验证受损的甘油三酯流,并探讨其与灰质体积、认知状态和脑淀粉样蛋白沉积之间的关系。方法:纳入80名接受了3T脑MRI(包括DTI和/或淀粉样蛋白PET)检查的AD患者(65人)和认知正常者(15人)(平均年龄76.9±8.5岁,女性57人)。在对年龄、性别、载脂蛋白 E 状态和白质高密度负担进行调整后,根据 AD 频谱对 ALPS 指数进行了比较。评估了ALPS指数与灰质体积、认知状态和PET定量淀粉样蛋白之间的关系。结果显示AD患者的ALPS指数(平均值,1.476;95% CI,1.395-1.556)明显低于CN患者(1.784;1.615-1.952;P = 0.026)。内叶皮层、海马、颞极和初级运动皮层的体积与 ALPS 指数有显著关联(均为 p <0.05)。ALPS-index 与 MMSE 评分呈正相关(部分 r = 0.435;p < 0.001),但 ALPS-index 与淀粉样蛋白 SUVR 之间无明显相关性(全部,p > 0.05)。结论通过DTI-ALPS测量到的AD患者血流减少可作为神经变性的标志物,与结构萎缩和认知能力下降相关。
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引用次数: 0
Complement Proteins in Serum Astrocyte-Derived Exosomes Are Associated with Poststroke Cognitive Impairment in Type 2 Diabetes Mellitus Patients 血清星形胶质细胞衍生外泌体中的补体蛋白与 2 型糖尿病患者卒中后的认知障碍有关
IF 4 3区 医学 Q1 Psychology Pub Date : 2024-04-19 DOI: 10.3233/jad-231235
Yaxuan Wu, Ming Tan, Yanling Gao, Na Geng, Weibin Zhong, Hairong Sun, Zhenguang Li, Chenxi Wu, Xuemei Li, Jinbiao Zhang
Background: The complement system plays crucial roles in cognitive impairment and acute ischemic stroke (AIS). High levels of complement proteins in plasma astrocyte-derived exosomes (ADEs) were proven to be associated with Alzheimer’s disease. We aimed to investigate the relationship of complement proteins in serum ADEs with poststroke cognitive impairment in type 2 diabetes mellitus (T2DM) patients. Methods: This study analyzed 197 T2DM patients who suffered AIS. The Beijing version of the Montreal Cognitive Assessment (MoCA) was used to assess cognitive function. Complement proteins in serum ADEs were quantified using ELISA kits. Results: Mediation analyses showed that C5b-9 and C3b in serum ADEs partially mediate the impact of obstructive sleep apnea (OSA), depression, small vessel disease (SVD), and infarct volume on cognitive function at the acute phase of AIS in T2DM patients. After adjusting for age, sex, time, and interaction between time and complement proteins in serum ADEs, the mixed linear regression showed that C3b and complement protein Factor B in serum ADEs were associated with MoCA scores at three-, six-, and twelve-months after AIS in T2DM patients. Conclusions: Our study suggested that the impact of OSA, depression, SVD, and infarct volume on cognitive impairment in the acute stage of AIS may partially mediate through the complement proteins in serum ADEs. Additionally, the complement proteins in serum ADEs at the acute phase of AIS associated with MoCA scores at three-, six-, twelve months after AIS in T2DM patients. REGISTRATION: URL: http://www.chictr.org.cn/,ChiCTR1900021544
背景:补体系统在认知障碍和急性缺血性中风(AIS)中起着至关重要的作用。血浆星形胶质细胞衍生外泌体(ADEs)中高水平的补体蛋白被证实与阿尔茨海默病有关。我们旨在研究血清 ADEs 中的补体蛋白与 2 型糖尿病(T2DM)患者卒中后认知障碍的关系。研究方法本研究分析了197名患有AIS的T2DM患者。采用北京版蒙特利尔认知评估(MoCA)评估认知功能。使用 ELISA 试剂盒对血清 ADE 中的补体蛋白进行量化。结果显示中介分析表明,血清ADEs中的C5b-9和C3b部分中介了阻塞性睡眠呼吸暂停(OSA)、抑郁、小血管疾病(SVD)和梗死体积对T2DM患者AIS急性期认知功能的影响。在对年龄、性别、时间以及时间与血清 ADE 中补体蛋白之间的交互作用进行调整后,混合线性回归结果显示,T2DM 患者血清 ADE 中的 C3b 和补体蛋白因子 B 与 AIS 后 3 个月、6 个月和 12 个月的 MoCA 评分相关。结论我们的研究表明,在 AIS 急性期,OSA、抑郁、SVD 和梗死体积对认知功能障碍的影响可能部分是通过血清 ADE 中的补体蛋白介导的。此外,AIS急性期血清ADEs中的补体蛋白与T2DM患者AIS后3、6、12个月的MoCA评分相关。注册: 网址: http://www.chictr.org.cn/,ChiCTR1900021544
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引用次数: 0
The RESIST Study: Examining Cognitive Change in Rheumatoid Arthritis Patients with Mild Cognitive Impairment Being Treated with a TNF-Inhibitor Compared to a Conventional Synthetic Disease-Modifying Anti-Rheumatic Drug RESIST 研究:与传统的合成改善病情抗风湿药相比,考察接受 TNF 抑制剂治疗的轻度认知障碍类风湿性关节炎患者的认知变化
IF 4 3区 医学 Q1 Psychology Pub Date : 2024-04-19 DOI: 10.3233/jad-231329
Calum Marr, Bethany McDowell, C. Holmes, Christopher J Edwards, Christopher Cardwell, M. Mchenry, Gary Meenagh, J. Teeling, B. McGuinness
Background: Evidence suggests that TNF inhibitors (TNFi) used to treat rheumatoid arthritis (RA) may protect against Alzheimer’s disease progression by reducing inflammation. Objective: To investigate whether RA patients with mild cognitive impairment (MCI) being treated with a TNFi show slower cognitive decline than those being treated with a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD). Methods: 251 participants with RA and MCI taking either a csDMARD (N = 157) or a TNFi (N = 94) completed cognitive assessments at baseline and 6-month intervals for 18 months. It was hypothesized that those taking TNFis would show less decline on the primary outcome of Free and Cued Selective Reminding Test with Immediate Recall (FCSRT-IR) and the secondary outcome of Montreal Cognitive Assessment (MoCA). Results: No significant changes in FCSRT-IR scores were observed in either treatment group. There was no significant difference in FCSRT-IR between treatment groups at 18 months after adjusting for baseline (mean difference = 0.5, 95% CI = –1.3, 2.3). There was also no difference in MoCA score (mean difference = 0.4, 95% CI = –0.4, 1.3). Conclusions: There was no cognitive decline in participants with MCI being treated with TNFis and csDMARDs, raising the possibility both classes of drug may be protective. Future studies should consider whether controlling inflammatory diseases using any approach is more important than a specific therapeutic intervention.
背景:有证据表明,用于治疗类风湿性关节炎(RA)的 TNF 抑制剂(TNFi)可通过减少炎症来预防阿尔茨海默病的进展。研究目的研究接受 TNFi 治疗的轻度认知障碍(MCI)RA 患者的认知能力下降速度是否慢于接受传统合成改善病情抗风湿药物(csDMARD)治疗的患者。方法:251名接受csDMARD(157人)或TNFi(94人)治疗的RA和MCI患者在18个月的基线期和每隔6个月完成一次认知评估。根据假设,服用TNFis的患者在 "立即回忆的自由和诱导选择性记忆测试"(FCSRT-IR)的主要结果和 "蒙特利尔认知评估"(MoCA)的次要结果上的下降幅度较小。结果两个治疗组的 FCSRT-IR 评分均无明显变化。在调整基线后,治疗组之间的 FCSRT-IR 在 18 个月时没有明显差异(平均差异 = 0.5,95% CI = -1.3, 2.3)。MoCA 评分也没有差异(平均差异 = 0.4,95% CI = -0.4,1.3)。结论接受TNFis和csDMARDs治疗的MCI患者的认知能力没有下降,因此这两类药物可能都具有保护作用。未来的研究应考虑使用任何方法控制炎症性疾病是否比特定的治疗干预更重要。
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引用次数: 0
Reduction in Constitutively Activated Auditory Brainstem Microglia in Aging and Alzheimer’s Disease 衰老和阿尔茨海默病中持续激活的听觉脑干小胶质细胞减少
IF 4 3区 医学 Q1 Psychology Pub Date : 2024-04-19 DOI: 10.3233/jad-231312
Tracy Butler, Xiuyuan H. Wang, Gloria C. Chiang, K. Xi, S. Niogi, Lidia Glodzik, Yi Li, Q. Razlighi, Liangdong Zhou, S. H. Hojjati, Ilker Ozsahin, Xiangling Mao, Thomas Maloney, E. Tanzi, N. Rahmouni, C. Tissot, Firoza Z. Lussier, Sudhin A. Shah, D. Shungu, Ajay Gupta, M. D. de Leon, P. D. Mozley, T. Pascoal, P. Rosa-Neto
Background: Alzheimer’s disease (AD) pathology is considered to begin in the brainstem, and cerebral microglia are known to play a critical role in AD pathogenesis, yet little is known about brainstem microglia in AD. Translocator protein (TSPO) PET, sensitive to activated microglia, shows high signal in dorsal brainstem in humans, but the precise location and clinical correlates of this signal are unknown. Objective: To define age and AD associations of brainstem TSPO PET signal in humans. Methods: We applied new probabilistic maps of brainstem nuclei to quantify PET-measured TSPO expression over the whole brain including brainstem in 71 subjects (43 controls scanned using 11C-PK11195; 20 controls and 8 AD subjects scanned using 11C-PBR28). We focused on inferior colliculi (IC) because of visually-obvious high signal in this region, and potential relevance to auditory dysfunction in AD. We also assessed bilateral cortex. Results: TSPO expression was normally high in IC and other brainstem regions. IC TSPO was decreased with aging (p = 0.001) and in AD subjects versus controls (p = 0.004) In cortex, TSPO expression was increased with aging (p = 0.030) and AD (p = 0.033). Conclusions: Decreased IC TSPO expression with aging and AD—an opposite pattern than in cortex—highlights underappreciated regional heterogeneity in microglia phenotype, and implicates IC in a biological explanation for strong links between hearing loss and AD. Unlike in cerebrum, where TSPO expression is considered pathological, activated microglia in IC and other brainstem nuclei may play a beneficial, homeostatic role. Additional study of brainstem microglia in aging and AD is needed.
背景:阿尔茨海默病(AD)的病理变化被认为始于脑干,已知脑小胶质细胞在AD发病机制中起着关键作用,但人们对AD中的脑干小胶质细胞知之甚少。对活化的小胶质细胞敏感的转座子蛋白(TSPO)PET在人类背侧脑干显示出高信号,但这一信号的确切位置和临床相关性尚不清楚。研究目的确定人类脑干 TSPO PET 信号与年龄和 AD 的关系。方法我们应用新的脑干核团概率图,对 71 名受试者(43 名对照组,使用 11C-PK11195 扫描;20 名对照组和 8 名 AD 受试者,使用 11C-PBR28 扫描)全脑(包括脑干)的 PET 测量 TSPO 表达进行量化。我们重点研究了下侧副神经体(IC),因为该区域在视觉上具有明显的高信号,而且可能与 AD 的听觉功能障碍有关。我们还评估了双侧皮层。结果TSPO在IC和其他脑干区域的表达通常很高。在大脑皮层中,TSPO 的表达随着年龄的增长而增加(p = 0.030),随着年龄的增长而增加(p = 0.033)。结论IC中TSPO的表达随衰老和AD而减少--与皮层中的模式相反--凸显了小胶质细胞表型中未被重视的区域异质性,并将IC与听力损失和AD之间密切联系的生物学解释联系了起来。在大脑中,TSPO 的表达被认为是病理性的,而在集成电路和其他脑干核中,活化的小胶质细胞可能发挥有益的平衡作用。还需要对脑干小胶质细胞在衰老和注意力缺失症中的作用进行更多研究。
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引用次数: 0
Could the Historical Transition from Segmented to Monophasic Sleep Explain the Modern Insurgence of Alzheimer’s Disease and Related Dementias? 从分段睡眠到单相睡眠的历史性转变能否解释现代阿尔茨海默病和相关痴呆症的肆虐?
IF 4 3区 医学 Q1 Psychology Pub Date : 2024-04-16 DOI: 10.3233/jad-240154
Nicola Luigi Bragazzi, Ayoub Boulares, Sergio Garbarino
In their article, Finch and Burstein explore the hypothesis that Alzheimer’s disease and related dementias (ADRD) may predominantly be phenomena of the modern era. Through a review of classical Greek and Latin literature, they found minimal reference to conditions akin to ADRD, suggesting a historical rarity of severe cognitive decline. Instead, ancient texts focused on physical aspects of aging, with cognitive changes, when noted, not resembling modern-day dementia. Finch and Burstein further extend their analysis by drawing parallels with the Tsimane people of Bolivia, known for their low prevalence of dementia and cardiovascular diseases, attributed to lifestyle factors such as diet and physical activity. By comparing historical sleep patterns transitioning from segmented to monophasic sleep with those of the Tsimane community, we enriched Finch and Burstein’s research, highlighting the need to take into account a range of diverse factors, including sleep, in understanding the etiopathogenesis of ADRD in today’s society.
芬奇和伯斯汀在文章中探讨了阿尔茨海默病和相关痴呆症(ADRD)可能主要是现代现象的假设。通过对古典希腊语和拉丁语文献的回顾,他们发现与 ADRD 类似的病症极少被提及,这表明严重认知功能衰退在历史上是罕见的。相反,古代文献侧重于衰老的生理方面,即使提到认知变化,也与现代痴呆症并不相似。芬奇和伯斯汀进一步扩展了他们的分析,将其与玻利维亚的齐玛尼人相提并论,齐玛尼人以痴呆症和心血管疾病发病率低而闻名,这归因于饮食和体育锻炼等生活方式因素。通过将历史上从分段睡眠过渡到单相睡眠的睡眠模式与Tsimane社区的睡眠模式进行比较,我们丰富了Finch和Burstein的研究,强调在理解当今社会ADRD的发病机制时,需要考虑包括睡眠在内的一系列不同因素。
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Journal of Alzheimer's Disease
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