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Age-related differences in how the shape of alpha and beta oscillations change during reaction time tasks 反应时间任务中阿尔法和贝塔振荡形状变化的年龄差异
IF 3.7 3区 医学 Q2 GERIATRICS & GERONTOLOGY Pub Date : 2024-08-13 DOI: 10.1016/j.neurobiolaging.2024.08.001
George M. Opie , James M. Hughes , Rohan Puri

While the shape of cortical oscillations is increasingly recognised to be physiologically and functionally informative, its relevance to the aging motor system has not been established. We therefore examined the shape of alpha and beta band oscillations recorded at rest, as well as during performance of simple and go/no-go reaction time tasks, in 33 young (23.3 ± 2.9 years, 27 females) and 27 older (60.0 ± 5.2 years, 23 females) adults. The shape of individual oscillatory cycles was characterised using a recently developed pipeline involving empirical mode decomposition, before being decomposed into waveform motifs using principal component analysis. This revealed four principal components that were uniquely influenced by task and/or age. These described specific dimensions of shape and tended to be modulated during the reaction phase of each task. Our results suggest that although oscillation shape is task-dependent, the nature of this effect is altered by advancing age, possibly reflecting alterations in cortical activity. These outcomes demonstrate the utility of this approach for understanding the neurophysiological effects of ageing.

尽管人们越来越认识到皮层振荡的形状在生理和功能上具有信息价值,但其与老化运动系统的相关性尚未得到证实。因此,我们研究了 33 名年轻人(23.3 ± 2.9 岁,27 名女性)和 27 名老年人(60.0 ± 5.2 岁,23 名女性)在静息状态下以及在完成简单和去/不去反应时间任务时记录到的α和β波段振荡的形状。在使用主成分分析法将单个振荡周期分解为波形图案之前,先使用最近开发的经验模式分解流水线对振荡周期的形状进行了表征。结果显示,有四个主成分受到任务和/或年龄的独特影响。这些主成分描述了形状的特定维度,并倾向于在每个任务的反应阶段进行调节。我们的结果表明,虽然振荡形状与任务有关,但这种影响的性质会随着年龄的增长而改变,这可能反映了大脑皮层活动的变化。这些结果证明了这种方法在理解老化的神经生理学影响方面的实用性。
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引用次数: 0
Explainable artificial intelligence identifies an AQP4 polymorphism-based risk score associated with brain amyloid burden 可解释人工智能确定了与脑淀粉样蛋白负荷相关的基于AQP4多态性的风险评分
IF 3.7 3区 医学 Q2 GERIATRICS & GERONTOLOGY Pub Date : 2024-08-10 DOI: 10.1016/j.neurobiolaging.2024.08.002
Simone Beer , David Elmenhorst , Gerard N. Bischof , Alfredo Ramirez , Andreas Bauer , Alexander Drzezga , for the Alzheimer’s Disease Neuroimaging Initiative

Aquaporin-4 (AQP4) is hypothesized to be a component of the glymphatic system, a pathway for removing brain interstitial solutes like amyloid-β (Aβ). Evidence exists that genetic variation of AQP4 impacts Aβ clearance, clinical outcome in Alzheimer’s disease as well as sleep measures. We examined whether a risk score calculated from several AQP4 single-nucleotide polymorphisms (SNPs) is related to Aβ neuropathology in older cognitively unimpaired white individuals. We used a machine learning approach and explainable artificial intelligence to extract information on synergistic effects of AQP4 SNPs on brain amyloid burden from the ADNI cohort. From this information, we formulated a sex-specific AQP4 SNP-based risk score and evaluated it using data from the screening process of the A4 study. We found in both cohorts significant associations of the risk score with brain amyloid burden. The results support the hypothesis of an involvement of the glymphatic system, and particularly AQP4, in brain amyloid aggregation pathology. They suggest also that different AQP4 SNPs exert a synergistic effect on the build-up of brain amyloid burden.

据推测,水蒸发素-4(AQP4)是glymphatic系统的一个组成部分,而glymphatic系统是清除淀粉样蛋白-β(Aβ)等脑间质溶质的一个途径。有证据表明,AQP4 的遗传变异会影响 Aβ 的清除、阿尔茨海默病的临床结果以及睡眠质量。我们研究了根据几个 AQP4 单核苷酸多态性(SNPs)计算出的风险评分是否与认知功能未受损的老年白人的 Aβ 神经病理学有关。我们使用机器学习方法和可解释人工智能从ADNI队列中提取了AQP4 SNPs对大脑淀粉样蛋白负荷协同效应的信息。根据这些信息,我们制定了基于 AQP4 SNP 的性别特异性风险评分,并利用 A4 研究筛选过程中的数据对其进行了评估。我们在两个队列中都发现了风险评分与脑淀粉样蛋白负荷的显著关联。这些结果支持了甘液系统,尤其是 AQP4 参与大脑淀粉样蛋白聚集病理学的假设。这些结果还表明,不同的 AQP4 SNPs 对大脑淀粉样蛋白负荷的积累具有协同作用。
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引用次数: 0
Editorial Advisory Board 编辑顾问委员会
IF 3.7 3区 医学 Q2 GERIATRICS & GERONTOLOGY Pub Date : 2024-07-14 DOI: 10.1016/S0197-4580(24)00127-1
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引用次数: 0
Lifespan differences in hippocampal subregion connectivity patterns during movie watching 观影过程中海马亚区连接模式的寿命差异
IF 3.7 3区 医学 Q2 GERIATRICS & GERONTOLOGY Pub Date : 2024-06-30 DOI: 10.1016/j.neurobiolaging.2024.06.006
Can Fenerci , Roni Setton , Giulia Baracchini , Jamie Snytte , R. Nathan Spreng , Cam CAN , Signy Sheldon

Age-related episodic memory decline is attributed to functional alternations in the hippocampus. Less clear is how aging affects the functional connections of the hippocampus to the rest of the brain during episodic memory processing. We examined fMRI data from the CamCAN dataset, in which a large cohort of participants watched a movie (N = 643; 18–88 years), a proxy for naturalistic episodic memory encoding. We examined connectivity profiles across the lifespan both within the hippocampus (anterior, posterior), and between the hippocampal subregions and cortical networks. Aging was associated with reductions in contralateral (left, right) but not ipsilateral (anterior, posterior) hippocampal subregion connectivity. Aging was primarily associated with increased coupling between the anterior hippocampus and regions affiliated with Control, Dorsal Attention and Default Mode networks, yet decreased coupling between the posterior hippocampus and a selection of these regions. Differences in age-related hippocampal-cortical, but not within-hippocampus circuitry selectively predicted worse memory performance. Our findings comprehensively characterize hippocampal functional topography in relation to cognition in older age, suggesting that shifts in cortico-hippocampal connectivity may be sensitive markers of age-related episodic memory decline.

与年龄有关的外显记忆衰退归因于海马体的功能变化。目前尚不清楚的是,衰老如何影响海马体在外显记忆处理过程中与大脑其他部分的功能连接。我们研究了来自 CamCAN 数据集的 fMRI 数据,在该数据集中,一大批参与者观看了一部电影(N = 643;18-88 岁),这是自然外显记忆编码的代表。我们研究了整个生命周期中海马内部(前部、后部)以及海马亚区与皮层网络之间的连接情况。衰老与海马对侧(左侧、右侧)而非同侧(前侧、后侧)海马亚区连通性的降低有关。衰老主要与海马前部和控制、背侧注意和默认模式网络附属区域之间的耦合增加有关,但与海马后部和这些区域中的某些区域之间的耦合减少有关。与年龄相关的海马-皮层(而非海马内部)回路差异可选择性地预测记忆表现的下降。我们的研究结果全面描述了与老年认知相关的海马功能拓扑,表明皮质-海马连接的变化可能是与年龄相关的记忆衰退的敏感标记。
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引用次数: 0
Reduced PIN1 expression in neocortical and limbic brain regions in female Alzheimer’s patients correlates with cognitive and neuropathological phenotypes 女性阿尔茨海默氏症患者新皮质和边缘脑区 PIN1 表达的减少与认知和神经病理学表型相关。
IF 3.7 3区 医学 Q2 GERIATRICS & GERONTOLOGY Pub Date : 2024-06-29 DOI: 10.1016/j.neurobiolaging.2024.06.007
Camila de Ávila , Crystal Suazo , Jennifer Nolz , J. Nicholas Cochran , Qi Wang , Ramon Velazquez , Eric Dammer , Benjamin Readhead , Diego Mastroeni

Women have a higher incidence of Alzheimer’s disease (AD), even after adjusting for increased longevity. Thus, there is an urgent need to identify genes that underpin sex-associated risk of AD. PIN1 is a key regulator of the tau phosphorylation signaling pathway; however, potential differences in PIN1 expression, in males and females, are still unknown. We analyzed brain transcriptomic datasets focusing on sex differences in PIN1 mRNA levels in an aging and AD cohort, which revealed reduced PIN1 levels primarily within females. We validated this observation in an independent dataset (ROS/MAP), which also revealed that PIN1 is negatively correlated with multiregional neurofibrillary tangle density and global cognitive function in females only. Additional analysis revealed a decrease in PIN1 in subjects with mild cognitive impairment (MCI) compared with aged individuals, again driven predominantly by female subjects. Histochemical analysis of PIN1 in AD and control male and female neocortex revealed an overall decrease in axonal PIN1 protein levels in females. These findings emphasize the importance of considering sex differences in AD research.

即使考虑到寿命的延长,女性阿尔茨海默病(AD)的发病率也更高。因此,我们迫切需要找出与性别相关的阿尔茨海默病风险基因。PIN1 是 tau 磷酸化信号通路的一个关键调节因子;然而,PIN1 在男性和女性中的潜在表达差异仍然未知。我们分析了大脑转录组数据集,重点研究了老年痴呆症队列中 PIN1 mRNA 水平的性别差异。我们在一个独立的数据集(ROS/MAP)中验证了这一观察结果,该数据集还显示,PIN1 与多区域神经纤维缠结密度和女性的整体认知功能呈负相关。其他分析表明,与老年患者相比,轻度认知障碍(MCI)患者的 PIN1 有所下降,同样主要是女性患者。对AD和对照组男性和女性新皮质中PIN1的组织化学分析显示,女性轴突PIN1蛋白水平总体下降。这些发现强调了在注意力缺失症研究中考虑性别差异的重要性。
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引用次数: 0
Age-related differences in retinal function and structure in C57BL/6J and Thy1-YFPh mice C57BL/6J 和 Thy1-YFPh 小鼠视网膜功能和结构的年龄相关性差异。
IF 3.7 3区 医学 Q2 GERIATRICS & GERONTOLOGY Pub Date : 2024-06-26 DOI: 10.1016/j.neurobiolaging.2024.06.005
Pei Ying Lee, Bang V. Bui

Age-related neuronal adaptations are known to help maintain function. This study aims to examine gross age-related in vivo retinal functional adaptations (using electroretinography) in young and middle aged C57BL/6J and Thy1-YFPh mice and to relate this to in vivo retinal structure (using optical coherence tomography). Electroretinography responses were generally larger in Thy1-YFPh mice than in C57BL/6J mice, with similar in vivo retinal layer thicknesses except for longer inner/outer photoreceptor segment in Thy1-YFPh mice. Relative to 3-month-old mice, 12-month-old mice showed reduced photoreceptor (C57BL/6J 84.0±2.5 %; Thy1-YFPh 80.2±5.2 %) and bipolar cell (C57BL/6J 75.6±2.3 %; Thy1-YFPh 68.1±5.5 %) function. There was relative preservation of ganglion cell function (C57BL/6J 79.7±3.7 %; Thy1-YFPh 91.7±5.0 %) with age, which was associated with increased b-wave (bipolar cell) sensitivities to light. Ganglion cell function was correlated with both b-wave amplitude and sensitivity. This study shows that there are normal age-related adaptations to preserve functional output. Different mouse strains may have varied age-related adaptation capacity and should be taken into consideration when examining age-related susceptibility to injury.

众所周知,与年龄相关的神经元适应有助于维持功能。本研究旨在检测年轻和中年C57BL/6J小鼠和Thy1-YFPh小鼠体内视网膜功能适应(使用视网膜电图)的粗略年龄相关性,并将其与体内视网膜结构(使用光学相干断层扫描)联系起来。Thy1-YFPh小鼠的视网膜电图反应一般比C57BL/6J小鼠大,体内视网膜层厚度相似,但Thy1-YFPh小鼠的内/外光感受器节段较长。与3月龄小鼠相比,12月龄小鼠的感光细胞(C57BL/6J 84.0±2.5%;Thy1-YFPh 80.2±5.2%)和双极细胞(C57BL/6J 75.6±2.3%;Thy1-YFPh 68.1±5.5%)功能降低。随着年龄的增长,神经节细胞功能相对保持不变(C57BL/6J 79.7±3.7%;Thy1-YFPh 91.7±5.0%),这与b波(双极细胞)对光的敏感性增加有关。神经节细胞功能与 b 波振幅和灵敏度相关。这项研究表明,存在与年龄相关的正常适应,以保持功能输出。不同的小鼠品系可能具有不同的与年龄相关的适应能力,在研究与年龄相关的损伤易感性时应加以考虑。
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引用次数: 0
Nonlinear age-related differences in probabilistic learning in mice: A 5-armed bandit task study 小鼠概率学习中与年龄有关的非线性差异:五臂强盗任务研究
IF 3.7 3区 医学 Q2 GERIATRICS & GERONTOLOGY Pub Date : 2024-06-26 DOI: 10.1016/j.neurobiolaging.2024.06.004
Hiroyuki Ohta , Takashi Nozawa , Takashi Nakano , Yuji Morimoto , Toshiaki Ishizuka

This study explores the impact of aging on reinforcement learning in mice, focusing on changes in learning rates and behavioral strategies. A 5-armed bandit task (5-ABT) and a computational Q-learning model were used to evaluate the positive and negative learning rates and the inverse temperature across three age groups (3, 12, and 18 months). Results showed a significant decline in the negative learning rate of 18-month-old mice, which was not observed for the positive learning rate. This suggests that older mice maintain the ability to learn from successful experiences while decreasing the ability to learn from negative outcomes. We also observed a significant age-dependent variation in inverse temperature, reflecting a shift in action selection policy. Middle-aged mice (12 months) exhibited higher inverse temperature, indicating a higher reliance on previous rewarding experiences and reduced exploratory behaviors, when compared to both younger and older mice. This study provides new insights into aging research by demonstrating that there are age-related differences in specific components of reinforcement learning, which exhibit a non-linear pattern.

本研究探讨了衰老对小鼠强化学习的影响,重点是学习率和行为策略的变化。研究使用五臂匪徒任务(5-ABT)和计算Q-学习模型评估了三个年龄组(3、12和18个月)小鼠的正负学习率和逆温。结果显示,18 个月大的小鼠的负向学习率明显下降,而正向学习率却没有下降。这表明,年龄较大的小鼠保持了从成功经验中学习的能力,同时降低了从负面结果中学习的能力。我们还观察到逆温随年龄的显著变化,这反映了行动选择政策的转变。与年轻小鼠和老年小鼠相比,中年小鼠(12 个月)表现出更高的逆温,表明它们更依赖于以前的奖励经验,探索行为减少。这项研究为老龄化研究提供了新的见解,证明强化学习的特定组成部分存在与年龄相关的差异,并呈现出非线性模式。
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引用次数: 0
Associations of cerebrovascular disease and Alzheimer’s disease pathology with cognitive decline: Analysis of the National Alzheimer’s Coordinating Center Uniform Data Set 脑血管疾病和阿尔茨海默病病理变化与认知能力下降的关系:国家阿尔茨海默氏症协调中心统一数据集分析
IF 3.7 3区 医学 Q2 GERIATRICS & GERONTOLOGY Pub Date : 2024-06-21 DOI: 10.1016/j.neurobiolaging.2024.06.002
Ankita Chatterjee , Shannon Lee , Valentina Diaz , Rowan Saloner , Mark Sanderson-Cimino , Charles deCarli , Pauline Maillard , Jason Hinman , Keith Vossel , Kaitlin B. Casaletto , Adam M. Staffaroni , Emily W. Paolillo , Joel H. Kramer

Cerebrovascular disease (CVD) and Alzheimer’s disease (AD) often co-occur and may impact specific cognitive domains. This study’s goal was to determine effects of CVD and AD burden on cross-sectional and longitudinal executive function (EF) and memory in older adults.

Longitudinally followed participants from the National Alzheimer Coordinating Center database (n = 3342) were included. Cognitive outcomes were EF and memory composite scores. Baseline CVD presence was defined by moderate-to-severe white matter hyperintensities or lacunar infarct on MRI. Baseline AD pathology was defined by amyloid positivity via PET or CSF. Linear mixed models examined effects of CVD, AD, and time on cognitive outcomes, controlling for sex, education, baseline age, MoCA score, and total number of study visits.

At baseline, CVD associated with lower EF (p < 0.001), while AD associated with lower EF and memory (ps < 0.001). Longitudinally only AD associated with faster declines in memory and EF (ps < 0.001).

These results extend our understanding of CVD and AD pathology, highlighting that CVD does not necessarily indicate accelerated decline.

脑血管疾病(CVD)和阿尔茨海默病(AD)经常同时发生,并可能影响特定的认知领域。本研究的目标是确定心血管疾病和阿尔茨海默病负担对老年人横截面和纵向执行功能(EF)和记忆的影响。认知结果为EF和记忆综合评分。基线心血管疾病定义为核磁共振成像中度至重度白质高密度或腔隙性梗死。AD病理学基线是指PET或CSF上的淀粉样蛋白阳性。线性混合模型检验了心血管疾病、AD和时间对认知结果的影响,同时控制了性别、教育程度、基线年龄、MoCA评分和研究访问总次数。这些结果扩展了我们对心血管疾病和注意力缺失症病理的认识,强调了心血管疾病并不一定预示着衰退加速。
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引用次数: 0
Multimodal investigation of neuropathology and neurometabolites in mild cognitive impairment and late-life depression with 11C-PiB beta-amyloid PET and 7T magnetic resonance spectroscopy 利用 11C-PiB beta-amyloid PET 和 7T 磁共振波谱对轻度认知障碍和晚年抑郁症的神经病理学和神经代谢物进行多模式研究。
IF 3.7 3区 医学 Q2 GERIATRICS & GERONTOLOGY Pub Date : 2024-06-20 DOI: 10.1016/j.neurobiolaging.2024.06.003
Christopher W. Davies-Jenkins , Clifford I. Workman , Kathleen E. Hupfeld , Helge J. Zöllner , Jeannie-Marie Leoutsakos , Michael A. Kraut , Peter B. Barker , Gwenn S. Smith , Georg Oeltzschner

Positron emission tomography (PET) and magnetic resonance spectroscopy (1H-MRS) are complementary techniques that can be applied to study how proteinopathy and neurometabolism relate to cognitive deficits in preclinical stages of Alzheimer’s disease (AD)—mild cognitive impairment (MCI) and late-life depression (LLD). We acquired beta-amyloid (Aβ) PET and 7 T 1H-MRS measures of GABA, glutamate, glutathione, N-acetylaspartate, N-acetylaspartylglutamate, myo-inositol, choline, and lactate in the anterior and posterior cingulate cortices (ACC, PCC) in 13 MCI and 9 LLD patients, and 13 controls. We used linear regression to examine associations between metabolites, Aβ, and cognitive scores, and whether metabolites and Aβ explained cognitive scores better than Aβ alone. In the ACC, higher Aβ was associated with lower GABA in controls but not MCI or LLD patients, but results depended upon MRS data quality control criteria. Greater variance in California Verbal Learning Test scores was better explained by a model that combined ACC glutamate and Aβ deposition than by models that only included one of these variables. These findings identify preliminary associations between Aβ, neurometabolites, and cognition.

正电子发射断层扫描(PET)和磁共振波谱(1H-MRS)是一种互补技术,可用于研究蛋白病变和神经代谢与阿尔茨海默病(AD)临床前阶段的认知障碍--轻度认知障碍(MCI)和晚年抑郁症(LLD)的关系。我们采集了 13 名 MCI 患者、9 名 LLD 患者和 13 名对照组患者前扣带回和后扣带回皮层(ACC、PCC)的β-淀粉样蛋白(Aβ)PET 和 7 T 1H-MRS 测量值,包括 GABA、谷氨酸、谷胱甘肽、N-乙酰天冬氨酸、N-乙酰天冬氨酸、肌醇、胆碱和乳酸盐。我们使用线性回归法研究了代谢物、Aβ和认知评分之间的关联,以及代谢物和Aβ是否比单独的Aβ更能解释认知评分。在ACC中,对照组中较高的Aβ与较低的GABA相关,而MCI或LLD患者则不相关,但结果取决于MRS数据质量控制标准。与只包含其中一个变量的模型相比,结合 ACC 谷氨酸和 Aβ 沉积的模型能更好地解释加利福尼亚言语学习测试得分的更大差异。这些发现初步确定了 Aβ、神经代谢物和认知之间的联系。
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引用次数: 0
Cerebrospinal fluid biomarkers and cognitive trajectories in patients with Alzheimer’s disease and a history of traumatic brain injury 阿尔茨海默病患者的脑脊液生物标志物和认知轨迹以及脑外伤史
IF 3.7 3区 医学 Q2 GERIATRICS & GERONTOLOGY Pub Date : 2024-06-14 DOI: 10.1016/j.neurobiolaging.2024.06.001
Suzan van Amerongen , Shreyasee Das , Suzie Kamps , Julie Goossens , Bram Bongers , Yolande A.L. Pijnenburg , Eugeen Vanmechelen , Everard G.B. Vijverberg , Charlotte E. Teunissen , Inge M.W. Verberk

Traumatic brain injury (TBI) and Alzheimer’s disease (AD) have overlapping mechanisms but it remains unknown if pathophysiological characteristics and cognitive trajectories in AD patients are influenced by TBI history. Here, we studied AD patients (stage MCI or dementia) with TBI history (ADTBI+, n=110), or without (ADTBI-, n=110) and compared baseline CSF concentrations of amyloid beta 1–42 (Aβ42), phosphorylated tau181 (pTau181), total tau, neurofilament light chain (NfL), synaptosomal associated protein-25kDa (SNAP25), neurogranin (Ng), neuronal pentraxin-2 (NPTX2) and glutamate receptor-4 (GluR4), as well as differences in cognitive trajectories using linear mixed models. Explorative, analyses were repeated within stratified TBI groups by TBI characteristics (timing, severity, number). We found no differences in baseline CSF biomarker concentrations nor in cognitive trajectories between ADTBI+ and ADTBI- patients. TBI >5 years ago was associated with higher NPTX2 and a tendency for higher SNAP25 concentrations compared to TBI ≤ 5 years ago, suggesting that TBI may be associated with long-term synaptic dysfunction only when occurring before onset or in a pre-clinical disease stage of AD.

创伤性脑损伤(TBI)和阿尔茨海默病(AD)的发病机制有重叠之处,但 AD 患者的病理生理学特征和认知轨迹是否受 TBI 史的影响仍是未知数。在此,我们研究了有 TBI 史(ADTBI+,n=110)或无 TBI 史(ADTBI-,n=110)的 AD 患者(MCI 或痴呆期),并比较了淀粉样 beta 1-42 (Aβ42)、磷酸化 tau181 (pTau181)、总 tau、神经纤维轻链(NfL)、突触体相关蛋白-25kDa(SNAP25)、神经粒蛋白(Ng)、神经元五肽-2(NPTX2)和谷氨酸受体-4(GluR4)的浓度,以及认知轨迹的差异。在按创伤性脑损伤特征(时间、严重程度、次数)分层的创伤性脑损伤组中,我们重复进行了探索性分析。我们发现ADTBI+和ADTBI-患者的基线CSF生物标志物浓度和认知轨迹均无差异。与≤5年前的创伤性脑损伤相比,5年前的创伤性脑损伤与较高的NPTX2和较高的SNAP25浓度有关,这表明创伤性脑损伤只有在AD发病前或临床前疾病阶段发生时才可能与长期突触功能障碍有关。
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引用次数: 0
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Neurobiology of Aging
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