Jillian L. Joyce, Arunima Kapoor, Megan S Barker, John Paul M Alitin, Allison C Engstrom, Trevor Lohman, Fatemah Shenasa, Aimée Gaubert, Farrah Ferrer, Amy Nguyen, Xingfeng Shao, Danny JJ Wang, Daniel A. Nation
Background
Apathy is a common neuropsychiatric symptom in Alzheimer's disease (AD) and cerebral small vessel disease, and is characterized by a pathological lack of motivation or interest in activities. It is often evident in the preclinical stages of disease, and individuals with apathy experience faster functional declines and poorer quality of life. Despite its clinical significance, the biological mechanisms underlying apathy are not well understood. Apathy has been associated with white matter hyperintensities of presumed vascular origin, warranting further investigation into vascular contributions to apathy. Cerebrovascular reactivity (CVR) provides a dynamic and functional measure of vascular health. CVR quantifies how effectively cerebral blood vessels modulate blood flow in response to vasoactive stimuli (i.e. CO2 increase during breath-hold). CVR deficits within the medial temporal lobe (MTL) are associated with poorer memory performance and greater risk of dementia. However, no prior work has investigated the association between apathy and CVR. In this study, we examined the association between CVR in the MTL and apathy in older individuals without dementia.
Method
This study included 121 community-dwelling older adults without dementia or stroke. Participants completed brain MRI and the Apathy Evaluation Scale (AES). Pseudo-continuous arterial spin labeling MRI quantified cerebral perfusion during breath-hold induced vasodilation (three 15-second visually guided breath holds) in the MTL (hippocampus and parahippocampal gyrus). Lower CVR values indicate reduced vasodilatory abilities and poorer vascular function. Linear regressions evaluated the relation between CVR and AES, with age as a covariate.
Result
Lower CVR abilities associated with greater apathy endorsement (β = -.250, p = .006). Age did not associate with CVR (β = -.045, p = .614).
Conclusion
These results highlight the link between vascular dysfunction and apathy among older adults. Impaired CVR in the MTL may be indicative of vascular dysfunction in this region, which could disrupt brain networks critical for goal-directed behavior, motivation, and emotion. Elucidating vascular contributions to apathy could inform interventions that improve functional outcomes and quality of life.
冷漠是阿尔茨海默病（AD）和脑血管疾病中常见的神经精神症状，其特征是病理性地缺乏活动的动机或兴趣。它通常在疾病的临床前阶段很明显，并且冷漠的个体经历更快的功能衰退和更差的生活质量。尽管其临床意义，冷漠的生物学机制尚不清楚。冷漠与假定的血管起源的白质高信号有关，因此需要进一步研究血管对冷漠的影响。脑血管反应性（CVR）是血管健康的动态和功能性指标。CVR量化了脑血管在响应血管活性刺激（即屏气时二氧化碳增加）时调节血流的有效性。内侧颞叶（MTL）内的CVR缺陷与较差的记忆表现和更大的痴呆风险相关。然而，之前没有研究冷漠与CVR之间的关系。在这项研究中，我们研究了无痴呆老年人MTL中CVR与冷漠之间的关系。方法：本研究纳入121名无痴呆或中风的社区老年人。参与者完成了脑MRI和冷漠评估量表（AES）。伪连续动脉自旋标记MRI量化了屏气诱导的MTL（海马和海马旁回）血管舒张（3次15秒的视觉引导屏气）期间的脑灌注。较低的CVR值表明血管舒张能力降低，血管功能较差。线性回归评估CVR和AES之间的关系，年龄作为协变量。结果较低的CVR能力与较高的冷漠认可相关(β =‐。250, p = .006)。年龄与CVR无关（β =‐）。045, p = .614)。结论这些结果强调了老年人血管功能障碍与冷漠之间的联系。MTL的CVR受损可能表明该区域的血管功能障碍，这可能会破坏对目标导向行为、动机和情绪至关重要的大脑网络。阐明血管对冷漠的影响可以为改善功能结果和生活质量的干预提供信息。
{"title":"Apathy and medial temporal lobe cerebrovascular reactivity","authors":"Jillian L. Joyce, Arunima Kapoor, Megan S Barker, John Paul M Alitin, Allison C Engstrom, Trevor Lohman, Fatemah Shenasa, Aimée Gaubert, Farrah Ferrer, Amy Nguyen, Xingfeng Shao, Danny JJ Wang, Daniel A. Nation","doi":"10.1002/alz70856_107043","DOIUrl":"10.1002/alz70856_107043","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Apathy is a common neuropsychiatric symptom in Alzheimer's disease (AD) and cerebral small vessel disease, and is characterized by a pathological lack of motivation or interest in activities. It is often evident in the preclinical stages of disease, and individuals with apathy experience faster functional declines and poorer quality of life. Despite its clinical significance, the biological mechanisms underlying apathy are not well understood. Apathy has been associated with white matter hyperintensities of presumed vascular origin, warranting further investigation into vascular contributions to apathy. Cerebrovascular reactivity (CVR) provides a dynamic and functional measure of vascular health. CVR quantifies how effectively cerebral blood vessels modulate blood flow in response to vasoactive stimuli (i.e. CO2 increase during breath-hold). CVR deficits within the medial temporal lobe (MTL) are associated with poorer memory performance and greater risk of dementia. However, no prior work has investigated the association between apathy and CVR. In this study, we examined the association between CVR in the MTL and apathy in older individuals without dementia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>This study included 121 community-dwelling older adults without dementia or stroke. Participants completed brain MRI and the Apathy Evaluation Scale (AES). Pseudo-continuous arterial spin labeling MRI quantified cerebral perfusion during breath-hold induced vasodilation (three 15-second visually guided breath holds) in the MTL (hippocampus and parahippocampal gyrus). Lower CVR values indicate reduced vasodilatory abilities and poorer vascular function. Linear regressions evaluated the relation between CVR and AES, with age as a covariate.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>Lower CVR abilities associated with greater apathy endorsement (<i>β</i> = -.250, <i>p</i> = .006). Age did not associate with CVR (<i>β</i> = -.045, <i>p</i> = .614).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These results highlight the link between vascular dysfunction and apathy among older adults. Impaired CVR in the MTL may be indicative of vascular dysfunction in this region, which could disrupt brain networks critical for goal-directed behavior, motivation, and emotion. Elucidating vascular contributions to apathy could inform interventions that improve functional outcomes and quality of life.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 S2","pages":""},"PeriodicalIF":11.1,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz70856_107043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145955179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Seokbeen Lim, Hoon-Ki Min, Jessica L. Brunn, David N. Soleimani-Meigooni, Hwamee Oh, Juan Fortea, Belen Pascual, Brian A. Gordon, Pedro Rosa-Neto, Suzanne L. Baker, Firoza Z Lussier, Guilherme Povala, Tharick A Pascoal, Val J Lowe
<div> <section> <h3> Background</h3> <p>The overlap index (OI), previously introduced by Lee et al. (2022), has proven to be a reliable method for detecting tau accumulation via tau-PET imaging with flortaucipir ([<sup>18</sup>F]AV-1451). This technique identifies voxel-wise increases in standardized uptake value ratio (SUVr) across serial scans. However, the relationship between tau-PET measurements obtained with [<sup>18</sup>F]MK-6240 and [<sup>18</sup>F]AV-1451 using the OI remains unclear. This study aims to investigate the relationship between [<sup>18</sup>F]MK-6240 and [<sup>18</sup>F]AV-1451 tau-PET using the tau-PET OI.</p> </section> <section> <h3> Method</h3> <p>The study included 27 participants from the HEAD project, all of whom underwent two serial tau-PET scans (each [<sup>18</sup>F]MK-6240 and [<sup>18</sup>F]AV-1451) along with 3T T1-weighted MRI, acquired within an average interval of 18 months. SUVr maps for each tau-PET tracer were normalized to the cerebellar crus grey matter, and MR images were co-registered to the MCALT T1 template. Tau-PET images were spatially resampled to the template space, and OI was computed within a predefined META-ROI using an intensity threshold of 1.3 and a cutoff of 0.5. Clusters containing fewer than 20 contiguous voxels were excluded from analysis. The META-ROI SUVr was calculated as the average SUVr across the selected region's SUVr. Additionally, a visual comparison was performed to assess the spatial overlap of OI-identified voxels between the two tau-PET tracers.</p> </section> <section> <h3> Result</h3> <p>OI values within the META-ROI exhibited a broad distribution between [<sup>18</sup>F]MK-6240 and [<sup>18</sup>F]AV-1451 tau-PET, particularly in cognitively unimpaired (CU) and younger individuals (Figure 1A). Unlike the OI distribution, the relationship between META-ROI SUVr values of both tracers followed an exponential trend (Figure 1B). Visual inspection revealed that OI-detected voxels in [<sup>18</sup>F]MK-6240 tau-PET were frequently localized to the meninges, an established site of off-target binding, which was not observed in [<sup>18</sup>F]AV-1451 tau-PET (Figure 2).</p> </section> <section> <h3> Conclusion</h3> <p>The association between [<sup>18</sup>F]MK-6240 and [<sup>18</sup>F]AV-1451 tau-PET, as assessed using the OI, exhibited considerable variability in CU and younger participants. Additionally, the presence of overlapping voxels in the meninges in [<sup>18</sup>F]MK-6240 tau-PET highlights the need to account for and potentially exclude off-target binding effects in t
Lee等人（2022）先前提出的重叠指数（OI）已被证明是通过flortaucipir的tau‐PET成像检测tau积累的可靠方法（[18 F]AV‐1451）。该技术通过串行扫描识别标准化摄取值比（SUVr）的体素增加。然而，用[18 F]MK - 6240和[18 F]AV - 1451测定的tau - PET之间的关系尚不清楚。本研究旨在利用tau - PET OI研究[18f]MK - 6240和[18f]AV - 1451 tau - PET之间的关系。方法：该研究纳入了来自HEAD项目的27名参与者，所有参与者均接受了两次连续的tau‐PET扫描（分别为[18 F]MK‐6240和[18 F]AV‐1451）以及3T T1加权MRI，平均间隔为18个月。每个tau - PET示踪剂的SUVr图谱归一化到小脑脚灰质，MR图像被共同注册到MCALT T1模板。Tau‐PET图像在空间上重新采样到模板空间，OI在预定义的META‐ROI内计算，强度阈值为1.3，截止值为0.5。包含少于20个连续体素的聚类被排除在分析之外。META - ROI SUVr计算为所选区域SUVr的平均SUVr。此外，还进行了视觉比较，以评估两种tau - PET示踪剂之间OI识别体素的空间重叠。结果META‐ROI内的OI值在[18 F]MK‐6240和[18 F]AV‐1451 tau‐PET之间表现出广泛的分布，特别是在认知未受损（CU）和年轻个体中（图1A）。与OI分布不同，两种示踪剂的META - ROI SUVr值之间的关系呈指数趋势（图1B）。目视检查显示，在[18 F]MK‐6240 tau‐PET中，OI‐检测到的体素经常定位于脑膜，这是一个已建立的脱靶结合位点，而在[18 F]AV‐1451 tau‐PET中没有观察到这一点（图2）。结论[18f]MK‐6240和[18f]AV‐1451 tau‐PET之间的相关性，通过OI评估，在CU和年轻参与者中表现出相当大的变异性。此外，[18 F]MK - 6240 tau - PET中脑膜中重叠体素的存在强调了需要考虑并可能排除这些人群中的脱靶结合效应。脑膜信号和其他脱靶结合对颞骨META - ROI中OI的影响有待进一步评估。
{"title":"Evaluation discrepancy between [18F]MK-6240 and [18F]AV-1451 tau-PET using tau-PET overlap index","authors":"Seokbeen Lim, Hoon-Ki Min, Jessica L. Brunn, David N. Soleimani-Meigooni, Hwamee Oh, Juan Fortea, Belen Pascual, Brian A. Gordon, Pedro Rosa-Neto, Suzanne L. Baker, Firoza Z Lussier, Guilherme Povala, Tharick A Pascoal, Val J Lowe","doi":"10.1002/alz70856_106145","DOIUrl":"10.1002/alz70856_106145","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The overlap index (OI), previously introduced by Lee et al. (2022), has proven to be a reliable method for detecting tau accumulation via tau-PET imaging with flortaucipir ([<sup>18</sup>F]AV-1451). This technique identifies voxel-wise increases in standardized uptake value ratio (SUVr) across serial scans. However, the relationship between tau-PET measurements obtained with [<sup>18</sup>F]MK-6240 and [<sup>18</sup>F]AV-1451 using the OI remains unclear. This study aims to investigate the relationship between [<sup>18</sup>F]MK-6240 and [<sup>18</sup>F]AV-1451 tau-PET using the tau-PET OI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>The study included 27 participants from the HEAD project, all of whom underwent two serial tau-PET scans (each [<sup>18</sup>F]MK-6240 and [<sup>18</sup>F]AV-1451) along with 3T T1-weighted MRI, acquired within an average interval of 18 months. SUVr maps for each tau-PET tracer were normalized to the cerebellar crus grey matter, and MR images were co-registered to the MCALT T1 template. Tau-PET images were spatially resampled to the template space, and OI was computed within a predefined META-ROI using an intensity threshold of 1.3 and a cutoff of 0.5. Clusters containing fewer than 20 contiguous voxels were excluded from analysis. The META-ROI SUVr was calculated as the average SUVr across the selected region's SUVr. Additionally, a visual comparison was performed to assess the spatial overlap of OI-identified voxels between the two tau-PET tracers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>OI values within the META-ROI exhibited a broad distribution between [<sup>18</sup>F]MK-6240 and [<sup>18</sup>F]AV-1451 tau-PET, particularly in cognitively unimpaired (CU) and younger individuals (Figure 1A). Unlike the OI distribution, the relationship between META-ROI SUVr values of both tracers followed an exponential trend (Figure 1B). Visual inspection revealed that OI-detected voxels in [<sup>18</sup>F]MK-6240 tau-PET were frequently localized to the meninges, an established site of off-target binding, which was not observed in [<sup>18</sup>F]AV-1451 tau-PET (Figure 2).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The association between [<sup>18</sup>F]MK-6240 and [<sup>18</sup>F]AV-1451 tau-PET, as assessed using the OI, exhibited considerable variability in CU and younger participants. Additionally, the presence of overlapping voxels in the meninges in [<sup>18</sup>F]MK-6240 tau-PET highlights the need to account for and potentially exclude off-target binding effects in t","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 S2","pages":""},"PeriodicalIF":11.1,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz70856_106145","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145955239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Neha Singh-Reilly, Stephen D. Weigand, Amanda Tapia, Ryota Satoh, Jonathan Graff-Radford, Mary M. Machulda, Christopher G Schwarz, Clifford R. Jack Jr., Val J Lowe, Keith A. Josephs, Jennifer L. Whitwell
<div> <section> <h3> Background</h3> <p>Atypical clinical presentations of Alzheimer's disease (AD) are associated with heterogeneous patterns of cortical tau-PET uptake. The medial-temporal (MTL) meta-ROI is typically used to determine tau-PET abnormality in AD, but this approach may not detect focal uptake in atypical patients. Our goal was to develop regional tau-PET cut-points and determine whether the number of positive regions better captures positive tau-PET signal in atypical AD.</p> </section> <section> <h3> Method</h3> <p>127 amyloid-positive atypical AD (visual=68, language=39, motor=15, others=5) and 62 amyloid-negative cognitively unimpaired (CU) individuals were recruited by the Neurodegenerative Research Group, Mayo Clinic, and underwent, amyloid-PET and <sup>18</sup>F-AV-1451(tau)-PET. Images were parcellated using the modified Harvard-Oxford atlas and we focused on 67 AD-specific regions. Rather than using the average SUVR across voxels within a region to quantify uptake, we used the 95<sup>th</sup> percentile of SUVR values across voxels within a region to capture focal cases. We then used receiver operating characteristic (ROC) methods and a Youden threshold to define regional abnormality. The number of abnormal regions was calculated for each participant and used to discriminate between CU and atypical AD at the individual level.</p> </section> <section> <h3> Result</h3> <p>Across 64 regions, our approach showed excellent (AUROC>0.90) differentiation between atypical AD and CU. The temporal-fusiform, parahippocampal gyrus and inferior temporal gyrus showed the best differentiation (Figure 1). All 67 regions showed excellent specificity (>85%), with 63 regions showing excellent sensitivity (≥80%). The lateral occipital cortex, temporal-fusiform and parahippocampal gyrus showed the best specificity and sensitivity (Figure 2). The distribution of the number of tau-elevated regions is shown in Figure 3. 74% of CU had no positive regions, while 43% of the atypical AD patients had all 67 regions affected. An optimal threshold of 7 tau-elevated regions classified all CU below, and 123 (97%) atypical AD above threshold. Using a standard approach based on the average SUVR in the MTL meta-ROI, only 116 (91%) atypical AD patients were tau-PET positive.</p> </section> <section> <h3> Conclusion</h3> <p>Tau uptake in temporal regions showed the greatest group-level differentiation. However, examining regional tau-positivity may offer better sensitivity in atypical AD patients compared to the temporal meta-ROI, likely due to the presence
背景：阿尔茨海默病（AD）的非典型临床表现与皮质tau‐PET摄取的异质性模式有关。内侧颞叶（MTL） meta ROI通常用于确定AD患者的tau - PET异常，但这种方法可能无法检测非典型患者的局灶性摄取。我们的目标是建立区域性的tau - PET切点，并确定在非典型AD中阳性区域的数量是否能更好地捕获阳性tau - PET信号。方法由梅奥诊所神经退行性研究小组招募了127例淀粉样蛋白阳性的非典型AD（视觉=68，语言=39，运动=15，其他=5）和62例淀粉样蛋白阴性的认知未受损（CU）个体，并进行了淀粉样蛋白- PET和18例F - AV - 1451(tau) - PET。使用改良的哈佛-牛津图谱对图像进行分割，我们将重点放在67个AD特异性区域。我们不是使用区域内体素间的平均SUVR来量化摄取，而是使用区域内体素间SUVR值的第95个百分位数来捕获焦点病例。然后，我们使用受试者工作特征（ROC）方法和约登阈值来定义区域异常。计算每个参与者的异常区域数量，并在个体水平上用于区分CU和非典型AD。结果在64个地区，我们的方法在非典型AD和CU之间显示出极好的鉴别（AUROC>0.90）。颞梭状回、海马旁回和颞下回表现出最好的分化（图1）。67个区域均表现出良好的特异性（>85%），其中63个区域表现出良好的敏感性（≥80%）。枕侧皮质、颞梭状回和海马旁回表现出最好的特异性和敏感性（图2）。tau‐升高区域的数量分布如图3所示。74%的CU无阳性区，而43%的非典型AD患者67个区均有感染。7个tau‐升高区域的最佳阈值将所有CU分类为低于阈值，123个（97%）非典型AD分类为高于阈值。使用基于MTL meta ROI平均SUVR的标准方法，只有116例（91%）非典型AD患者tau‐PET阳性。结论Tau蛋白摄取在颞区表现出最大的群体分化。然而，在非典型AD患者中，与时间元ROI相比，检测区域tau阳性可能提供更好的敏感性，这可能是由于存在局灶性非时间摄取模式。
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Roberta Lizio, Claudio Del Percio, Susanna Lopez, Mina De Bartolo, Matteo Carpi, Antonio Pio Afragola, Giuseppe Noce, Raffaele Ferri, Bahar Güntekin, Görsev Yener, Claudio Babiloni
Background
Patients with mild cognitive impairment (MCI) typically show abnormal high delta (<4 Hz) and low alpha (8–12 Hz) rhythms measured from resting-state eyes-closed electroencephalographic (rsEEG) source activities as well as white matter lesions (WMLs) measured from magnetic resonance imaging (MRI). Here we tested the hypothesis that rsEEG rhythms may not deteriorate with the increase of WLMs in patients with MCI due and not due to Alzheimer's disease (ADMCI and noADMCI).
Method
An international database provided demographic, clinical, and rsEEG datasets for cognitively unimpaired older (Healthy; N = 30), ADMCI (N = 64), and noADMCI (N = 36) participants. The rsEEG rhythms spanned individual delta, theta, and alpha frequency bands. The eLORETA freeware estimated cortical rsEEG sources. The international database also provided MRI datasets for the ADMCI and noADMCI participants. T2 and Fluid Attenuated Inversion Recovery (FLAIR) images estimated the WMLs.
Result
The posterior rsEEG alpha source activities were lower in the groups of the ADMCI with a less increase of WMLs (ADMCI-WML-), ADMCI with a high increase of WMLs (ADMCI-WML+), and noADMCI with a very high increase of WMLs (noADMCI-WL++) compared to the Healthy group (p < 0.001; Figure 1). This effect was dramatic in the ADMCI-WML- group, marked in the ADMCI-WML+ group, and moderate in the noADMCI-WML++. Furthermore, a positive association between the increase of WMLs and the worsening of executive function test scores (i.e., Trail making test part B-A) was observed in the noADMCI group (t = 3.25, p < 0.005; Figure 2).
Conclusion
These results suggest that neurophysiological brain neural oscillatory synchronization mechanisms regulating cortical arousal and vigilance through alpha rsEEG rhythms are not affected by white matter tissue damage in MCI patients.
背景：轻度认知障碍（MCI）患者通常表现出异常的高δ (< 4hz)和低α (8 - 12hz)节律，这是通过静息状态闭眼脑电图（rsEEG）源活动以及通过磁共振成像（MRI）测量的白质病变（WMLs）来测量的。在这里，我们验证了一种假设，即在MCI患者（ADMCI和noADMCI）中，rsEEG节律可能不会随着WLMs的增加而恶化，而不是由于阿尔茨海默病（ADMCI和noADMCI）。方法一个国际数据库提供了认知功能未受损的老年人（健康；N = 30）、ADMCI （N = 64）和非ADMCI （N = 36）参与者的人口学、临床和rsEEG数据集。rsEEG节律跨越了单独的δ、θ和α频段。eLORETA免费软件估计皮质rsEEG源。国际数据库还提供了ADMCI和noADMCI参与者的MRI数据集。T2和流体衰减反演恢复（FLAIR）图像估计wml。结果与健康组相比，WML增加较少的ADMCI组（ADMCI‐WML‐）、WML增加较多的ADMCI组（ADMCI‐WML+）和WML增加较多的noADMCI组（noADMCI‐WML+ +）后rsEEG α源活性较低（p < 0.001；图1）。这种效果在ADMCI - WML -组中显著，在ADMCI - WML+组中显著，在noADMCI - WML++组中中等。此外，在noADMCI组中，WMLs的增加与执行功能测试分数（即Trail making test part B‐a）的恶化之间存在正相关（t = 3.25, p < 0.005；图2）。结论MCI患者通过α - rsEEG节律调节皮层觉醒和警觉性的神经生理脑神经振荡同步机制不受白质组织损伤的影响。
{"title":"Abnormalities of resting-state eyes-closed electroencephalographic rhythms are not affected by white matter lesions in patients with mild cognitive impairment due and not due to Alzheimer's disease","authors":"Roberta Lizio, Claudio Del Percio, Susanna Lopez, Mina De Bartolo, Matteo Carpi, Antonio Pio Afragola, Giuseppe Noce, Raffaele Ferri, Bahar Güntekin, Görsev Yener, Claudio Babiloni","doi":"10.1002/alz70856_106342","DOIUrl":"10.1002/alz70856_106342","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Patients with mild cognitive impairment (MCI) typically show abnormal high delta (<4 Hz) and low alpha (8–12 Hz) rhythms measured from resting-state eyes-closed electroencephalographic (rsEEG) source activities as well as white matter lesions (WMLs) measured from magnetic resonance imaging (MRI). Here we tested the hypothesis that rsEEG rhythms may not deteriorate with the increase of WLMs in patients with MCI due and not due to Alzheimer's disease (ADMCI and noADMCI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>An international database provided demographic, clinical, and rsEEG datasets for cognitively unimpaired older (Healthy; N = 30), ADMCI (<i>N</i> = 64), and noADMCI (<i>N</i> = 36) participants. The rsEEG rhythms spanned individual delta, theta, and alpha frequency bands. The eLORETA freeware estimated cortical rsEEG sources. The international database also provided MRI datasets for the ADMCI and noADMCI participants. T2 and Fluid Attenuated Inversion Recovery (FLAIR) images estimated the WMLs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>The posterior rsEEG alpha source activities were lower in the groups of the ADMCI with a less increase of WMLs (ADMCI-WML-), ADMCI with a high increase of WMLs (ADMCI-WML+), and noADMCI with a very high increase of WMLs (noADMCI-WL++) compared to the Healthy group (<i>p</i> < 0.001; <i>Figure 1</i>). This effect was dramatic in the ADMCI-WML- group, marked in the ADMCI-WML+ group, and moderate in the noADMCI-WML++. Furthermore, a positive association between the increase of WMLs and the worsening of executive function test scores (i.e., Trail making test part B-A) was observed in the noADMCI group (t = 3.25, <i>p</i> < 0.005; <i>Figure 2</i>).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These results suggest that neurophysiological brain neural oscillatory synchronization mechanisms regulating cortical arousal and vigilance through alpha rsEEG rhythms are not affected by white matter tissue damage in MCI patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 S2","pages":""},"PeriodicalIF":11.1,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz70856_106342","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145955336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alzheimer's disease (AD) profoundly affects motor control and cognitive functions, often resulting in impaired speech characteristics such as vocal clarity, emotional expressiveness, and prosodic richness. To detect such abnormalities, we examine the role of three specific acoustic features to differentiate participants with AD from healthy controls (HC) and study the association between these acoustic features and global cognition.
Methods
Speech data from 237 participants (115 HC, 110 AD) in the ADReSS-M dataset, collected during the “Cookie Theft” picture description task, were analyzed. This dataset has been matched for age and gender by propensity score to prevent bias. The HC group averaged 66.4 years (SD: 6.64), and the AD group averaged 69.4 years (SD: 6.92), with significantly lower Mini-Mental State Examination (MMSE) scores in AD (AD: 17.9; HC: 29.0). Features quantifying vocal clarity, articulatory precision (spectral contrast), vocal tone (pitch mean), and prosodic variability (pitch standard deviation) were extracted. Group differences in these features were assessed using t-tests, and Pearson correlation analyses were conducted to examine associations between acoustic measures and MMSE scores.
Results
There were significant differences between AD and HC groups for spectral contrast (t(235) = 4.26, p <0.0001), pitch mean (t(235) = 3.54, p = 0.0005), and pitch standard deviation (t(235) = 3.62, p = 0.0004). Cohen's d values for these features ranged from -0.5 to -0.6, indicating medium effect sizes, with lower values observed in the AD group. We also found a significant correlation (p <0.01) between MMSE scores and each of the features (Pearson's r = 0.22 for pitch mean, 0.23 for pitch standard deviation, and 0.25 for spectral contrast).
Conclusions
This preliminary study highlights the physiological basis of altered speech patterns in AD and their diagnostic relevance. Future work will focus on refining preprocessing algorithms and incorporating advanced feature extraction methods to enhance the effect sizes and correlation for AD detection and cognitive assessment.
阿尔茨海默病（AD）严重影响运动控制和认知功能，通常导致语音特征受损，如声音清晰度，情绪表达能力和韵律丰富度。为了检测这种异常，我们研究了三种特定的声学特征在区分AD参与者和健康对照组（HC）中的作用，并研究了这些声学特征与整体认知之间的关系。方法对address‐M数据集中237名参与者（115名HC， 110名AD）在“Cookie盗窃”图片描述任务中收集的语音数据进行分析。该数据集已通过倾向得分匹配年龄和性别，以防止偏差。HC组平均66.4岁（SD: 6.64）， AD组平均69.4岁（SD: 6.92）， AD的Mini - Mental State Examination （MMSE）得分显著低于HC组（AD: 17.9; HC: 29.0）。提取量化嗓音清晰度、发音精度（频谱对比）、声调（音高均值）和韵律变异性（音高标准差）的特征。使用t检验评估这些特征的组间差异，并进行Pearson相关分析以检查声学测量与MMSE评分之间的关联。结果AD组与HC组的光谱对比度（t(235) = 4.26, p <0.0001）、平均音高（t(235) = 3.54, p = 0.0005）、音高标准差（t(235) = 3.62, p = 0.0004）差异均有统计学意义。这些特征的Cohen’s d值范围为‐0.5 ~‐0.6，表明效应大小中等，AD组的效应值较低。我们还发现MMSE分数与每个特征之间存在显著相关性（p <0.01）（音调平均值的Pearson's r = 0.22，音调标准差的Pearson's r = 0.23，光谱对比度的Pearson's r = 0.25）。结论本初步研究强调了AD患者言语模式改变的生理基础及其诊断意义。未来的工作将集中在改进预处理算法和结合先进的特征提取方法，以增强AD检测和认知评估的效应大小和相关性。
{"title":"Speech-Based Detection of Alzheimer's Disease: Leveraging Spectral Contrast and Pitch Variability as Potential Diagnostic Markers","authors":"Hamed Azami, Saturnino Luz, Sanjeev Kumar","doi":"10.1002/alz70856_106182","DOIUrl":"10.1002/alz70856_106182","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alzheimer's disease (AD) profoundly affects motor control and cognitive functions, often resulting in impaired speech characteristics such as vocal clarity, emotional expressiveness, and prosodic richness. To detect such abnormalities, we examine the role of three specific acoustic features to differentiate participants with AD from healthy controls (HC) and study the association between these acoustic features and global cognition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Speech data from 237 participants (115 HC, 110 AD) in the ADReSS-M dataset, collected during the “Cookie Theft” picture description task, were analyzed. This dataset has been matched for age and gender by propensity score to prevent bias. The HC group averaged 66.4 years (SD: 6.64), and the AD group averaged 69.4 years (SD: 6.92), with significantly lower Mini-Mental State Examination (MMSE) scores in AD (AD: 17.9; HC: 29.0). Features quantifying vocal clarity, articulatory precision (spectral contrast), vocal tone (pitch mean), and prosodic variability (pitch standard deviation) were extracted. Group differences in these features were assessed using t-tests, and Pearson correlation analyses were conducted to examine associations between acoustic measures and MMSE scores.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There were significant differences between AD and HC groups for spectral contrast (t(235) = 4.26, <i>p</i> <0.0001), pitch mean (t(235) = 3.54, <i>p</i> = 0.0005), and pitch standard deviation (t(235) = 3.62, <i>p</i> = 0.0004). Cohen's d values for these features ranged from -0.5 to -0.6, indicating medium effect sizes, with lower values observed in the AD group. We also found a significant correlation (<i>p</i> <0.01) between MMSE scores and each of the features (Pearson's r = 0.22 for pitch mean, 0.23 for pitch standard deviation, and 0.25 for spectral contrast).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This preliminary study highlights the physiological basis of altered speech patterns in AD and their diagnostic relevance. Future work will focus on refining preprocessing algorithms and incorporating advanced feature extraction methods to enhance the effect sizes and correlation for AD detection and cognitive assessment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 S2","pages":""},"PeriodicalIF":11.1,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz70856_106182","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145947315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jason K. Russell, Zinayida Schlachetzki, Alexander C. Conley, Brian D. Boyd, Paul A. Newhouse, Paul S. Aisen, Michael S. Rafii, for the Alzheimer's Biomarker Consortium on Down Syndrome Study
INTRODUCTION
Adults with Down syndrome (DS) display increased Alzheimer's disease (AD) risk. The cholinergic system declines early in the AD continuum and relates to cognitive and functional decline. We aimed to identify the timeline of cholinergic decline in relation to hippocampal atrophy within the AT(N) framework in DS.
METHODS
Three-hundred fifty-eight adults with DS were assessed for longitudinal changes in cholinergic basal forebrain and hippocampal volume, amyloid positron emission tomography (PET), tau PET, and cognitive performance.
RESULTS
Amyloid PET increased at 36.5 years old, while tau accumulation, cholinergic basal forebrain (ChBF), and hippocampal volumetric changes occurred in the participants’ 40s. Cognitive decline on the modified cued recall test initiated at 41.7 years old. ChBF and hippocampal volumes negatively associated with AD pathology and positively associated with cognitive performance, with ChBF effects moderated by hippocampal volume.
DISCUSSION
The timeline presented will inform the design of clinical trials targeting the cholinergic system or utilizing volumetric measures as biomarkers of efficacy or cognition.
Highlights
The first longitudinal assessment of cholinergic basal forebrain and hippocampal volume in DSAD.
The AT(N) framework utilized sporadic AD is consistent in DSAD.
Cholinergic basal forebrain volume is an alternate measure of neurodegeneration in the AT(N) framework.
Cholinergic effects on total recall on the mCRT are moderated by the hippocampus.
{"title":"Relationship of cholinergic basal forebrain atrophy with the time course of Alzheimer's disease pathology and cognitive decline in adults with Down syndrome: a longitudinal cohort study","authors":"Jason K. Russell, Zinayida Schlachetzki, Alexander C. Conley, Brian D. Boyd, Paul A. Newhouse, Paul S. Aisen, Michael S. Rafii, for the Alzheimer's Biomarker Consortium on Down Syndrome Study","doi":"10.1002/alz.71028","DOIUrl":"10.1002/alz.71028","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Adults with Down syndrome (DS) display increased Alzheimer's disease (AD) risk. The cholinergic system declines early in the AD continuum and relates to cognitive and functional decline. We aimed to identify the timeline of cholinergic decline in relation to hippocampal atrophy within the AT(N) framework in DS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Three-hundred fifty-eight adults with DS were assessed for longitudinal changes in cholinergic basal forebrain and hippocampal volume, amyloid positron emission tomography (PET), tau PET, and cognitive performance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Amyloid PET increased at 36.5 years old, while tau accumulation, cholinergic basal forebrain (ChBF), and hippocampal volumetric changes occurred in the participants’ 40s. Cognitive decline on the modified cued recall test initiated at 41.7 years old. ChBF and hippocampal volumes negatively associated with AD pathology and positively associated with cognitive performance, with ChBF effects moderated by hippocampal volume.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The timeline presented will inform the design of clinical trials targeting the cholinergic system or utilizing volumetric measures as biomarkers of efficacy or cognition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The first longitudinal assessment of cholinergic basal forebrain and hippocampal volume in DSAD.</li>\u0000 \u0000 <li>The AT(N) framework utilized sporadic AD is consistent in DSAD.</li>\u0000 \u0000 <li>Cholinergic basal forebrain volume is an alternate measure of neurodegeneration in the AT(N) framework.</li>\u0000 \u0000 <li>Cholinergic effects on total recall on the mCRT are moderated by the hippocampus.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"22 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.71028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145951281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jeremy A. Tanner, Sophia Lu, Hugo J. Aparicio, Sara Doyle, Mitzi M. Gonzales, Jayandra Jung Himali, Tiffany F. Kautz, Terrie-Jeanne Liu, Pauline Maillard, Emer McGrath, Jaime Ramos-Cejudo, Claudia L Satizabal, Russell P. Tracy, Mohamad Habes, Suzanne E. Schindler, Charles Decarli, Alexa S Beiser, Sudha Seshadri
<div> <section> <h3> Background</h3> <p>Plasma ADRD biomarkers are emerging as accessible and cost-effective diagnostic tools, but data on their relevance in the general population is needed prior to widespread use. Plasma Ptau shows potential for AD screening, yet its association with structural brain changes in community-based populations remains unclear. Similarly, it is unclear if plasma NfL and GFAP more closely reflect vascular disease or neurodegeneration, and whether this differs in those with, versus without, AD. This study assesses:(1) the association between plasma Ptau181 and brain MRI outcomes and(2) whether elevated Ptau181 modifies the relationship between NfL, GFAP, and brain MRI features in the Framingham Heart Study(FHS), a flagship population-based cohort.</p> </section> <section> <h3> Method</h3> <p>FHS Offspring and Omni 1 Cohort participants (Exam 9;2011-2014) with available plasma biomarkers, brain MRI, and no confounding neurologic disorders were included. Plasma Ptau181, GFAP, and NfL were measured using Quanterix Simoa. MRI outcomes included measures of vascular disease, neurodegeneration, AD-pattern atrophy, and white matter disease. Plasma Ptau181 was analyzed as a continuous and binary predictor (highest quintile vs remainder) using multivariate linear regressions adjusted for age, age<sup>2</sup>, sex, eGFR, and MRI-plasma collection interval, with FDR correction. Additional models assessed GFAP and NfL as continuous predictors, stratified by Ptau181 level (highest quintile vs remainder). Sensitivity analyses excluded participants with dementia and/or stroke.</p> </section> <section> <h3> Result</h3> <p>1183 participants were included (mean age 69±8, 56%Female, mean MMSE 29±1.6). Elevated Ptau181 was associated with AD-pattern cortical thickness in primary and all sensitivity analyses, and with cortical atrophy in primary though not all sensitivity analyses (Table 1). Elevated GFAP was most strongly associated with worsened AD-pattern atrophy and cortical atrophy in individuals with elevated Ptau181, and with periventricular white matter hyperintensities(WMH) in those with low Ptau181(Table 2). Elevated NfL was associated with AD-pattern and cortical atrophy in those with/without elevated Ptau181, and additionally with extensive WMH in those with elevated PTau181(Table 3).</p> </section> <section> <h3> Conclusion</h3> <p>The combination of plasma Ptau181, GFAP, and NfL provide information on the etiology and severity of brain disease in the community. In AD, each are associated with worsening neurodegeneration severity
{"title":"Plasma Ptau as a Biomarker of Structural Brain Health in the Community","authors":"Jeremy A. Tanner, Sophia Lu, Hugo J. Aparicio, Sara Doyle, Mitzi M. Gonzales, Jayandra Jung Himali, Tiffany F. Kautz, Terrie-Jeanne Liu, Pauline Maillard, Emer McGrath, Jaime Ramos-Cejudo, Claudia L Satizabal, Russell P. Tracy, Mohamad Habes, Suzanne E. Schindler, Charles Decarli, Alexa S Beiser, Sudha Seshadri","doi":"10.1002/alz70856_106409","DOIUrl":"10.1002/alz70856_106409","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Plasma ADRD biomarkers are emerging as accessible and cost-effective diagnostic tools, but data on their relevance in the general population is needed prior to widespread use. Plasma Ptau shows potential for AD screening, yet its association with structural brain changes in community-based populations remains unclear. Similarly, it is unclear if plasma NfL and GFAP more closely reflect vascular disease or neurodegeneration, and whether this differs in those with, versus without, AD. This study assesses:(1) the association between plasma Ptau181 and brain MRI outcomes and(2) whether elevated Ptau181 modifies the relationship between NfL, GFAP, and brain MRI features in the Framingham Heart Study(FHS), a flagship population-based cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>FHS Offspring and Omni 1 Cohort participants (Exam 9;2011-2014) with available plasma biomarkers, brain MRI, and no confounding neurologic disorders were included. Plasma Ptau181, GFAP, and NfL were measured using Quanterix Simoa. MRI outcomes included measures of vascular disease, neurodegeneration, AD-pattern atrophy, and white matter disease. Plasma Ptau181 was analyzed as a continuous and binary predictor (highest quintile vs remainder) using multivariate linear regressions adjusted for age, age<sup>2</sup>, sex, eGFR, and MRI-plasma collection interval, with FDR correction. Additional models assessed GFAP and NfL as continuous predictors, stratified by Ptau181 level (highest quintile vs remainder). Sensitivity analyses excluded participants with dementia and/or stroke.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>1183 participants were included (mean age 69±8, 56%Female, mean MMSE 29±1.6). Elevated Ptau181 was associated with AD-pattern cortical thickness in primary and all sensitivity analyses, and with cortical atrophy in primary though not all sensitivity analyses (Table 1). Elevated GFAP was most strongly associated with worsened AD-pattern atrophy and cortical atrophy in individuals with elevated Ptau181, and with periventricular white matter hyperintensities(WMH) in those with low Ptau181(Table 2). Elevated NfL was associated with AD-pattern and cortical atrophy in those with/without elevated Ptau181, and additionally with extensive WMH in those with elevated PTau181(Table 3).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The combination of plasma Ptau181, GFAP, and NfL provide information on the etiology and severity of brain disease in the community. In AD, each are associated with worsening neurodegeneration severity","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 S2","pages":""},"PeriodicalIF":11.1,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz70856_106409","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145955161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carolina Soares, Emma Ruppert, Pamela C.L. Ferreira, Marina Scop Madeiros, Andreia Rocha, Matheus Scarpatto Rodrigues, Bruna Bellaver, Markley Silva Oliveira Jr., Guilherme Povala, Livia Amaral, Firoza Z Lussier, Joseph C. Masdeu, Dana L Tudorascu, Thomas K Karikari, David N. Soleimani-Meigooni, Juan Fortea, Val J Lowe, Hwamee Oh, Belen Pascual, Brian A. Gordon, Pedro Rosa-Neto, Suzanne L. Baker, Tharick A Pascoal
<div> <section> <h3> Background</h3> <p>Older adults with brain tau pathology but no evident amyloid-beta (A) pathology can be referred to as primary age-related tauopathy (PART). However, in vivo characterization of PART using biomarkers remains unclear, varying based on the method used to define tau pathology (e.g. different tau-PET tracers). Here, we conducted a head-to-head characterization of PART using two different tau-PET tracers.</p> </section> <section> <h3> Method</h3> <p>We studied 433 individuals from the HEAD cohort (244 CU, 138 MCI, and 51 with dementia). Participants underwent clinical assessments, MRI, A-PET, both MK-6240 and Flortaucipir scans, and a subset with plasma biomarkers (<i>n</i> = 332). A-PET positivity was defined as Centiloid>24. Tau-positivity(T) was determined by MK-6240 and Flortaucipir SUVR values exceeding the mean+2SD in at least one Braak region anchored in CU A- individuals followed by visual confirmation in A-/T+ cases. Concordance across biomarkers was assessed among PART (A-/T+), A-/T- and A+/T+ groups. Plasma GFAP, <i>p</i>-tau217, NFL levels, and Centiloids were compared across A/T groups using linear regression.</p> </section> <section> <h3> Result</h3> <p>We found a total of 25 (5.8 %) cases classified as A-/T+ defined by at least one tau tracer (74±6.3 years, 52% females, 17 CU, 3 MCI, 5 with dementia). Detection of A-/T+ cases varied by tracer: MK-6240(<i>n</i> = 20), Flortaucipir(<i>n</i> = 16) (Figure 1A). Among A-/T+ individuals, MK-6240 identified 13 CU, 4 MCI, and 3 dementia cases, while Flortaucipir identified 11 CU, 3 MCI, and 2 dementia cases(Figure 1B). Concordance between MK-6240 and Flortaucipir in A-/T+ cases was low (<i>n</i> = 11, 44%)(Figure 1C). A-/T+ individuals showed no significant biomarker differences from A-/T- but had lower biomarker levels than A+/T+: Centiloids (MK-6240: T=15.08, <i>p</i> <0.001; Flortaucipir: T=14.36, <i>p</i> <0.001), GFAP (MK-6240: T=5.04, <i>p</i> < 0.01; Flortaucipir: T=2.92, <i>p</i> <0.001), <i>p</i>-tau217 (MK-6240: T=7.77, <i>p</i> <0.001; Flortaucipir: T=6.34, <i>p</i> <0.001), except for NFL (MK-6240: T=1.35, <i>p</i> = 0.18; Flortaucipir: T=1.14, <i>p</i> = 0.25)(Figure 2). Representative A and tau biomarker cases (Figure 3A), along with discordant cases classified as T+ by only one tracer (Figure 3B), are illustrated.</p> </section> <section> <h3> Conclusion</h3> <p>Our preliminary analysis revealed a higher prevalence of A-/T+ cases with MK-6240 than Flortaucipir, low concordance between tracers and consistently lower biomark
背景：有脑tau病理但没有明显淀粉样蛋白(A)病理的老年人可被称为原发性年龄相关性tau病（PART）。然而，使用生物标志物对PART的体内表征仍然不清楚，根据用于定义tau病理学的方法（例如不同的tau‐PET示踪剂）而有所不同。在这里，我们使用两种不同的tau - PET示踪剂对PART进行了头部对头部的表征。方法我们研究了来自HEAD队列的433名个体（244名CU， 138名MCI和51名痴呆患者）。参与者接受了临床评估、MRI、A‐PET、MK‐6240和Flortaucipir扫描，以及血浆生物标志物亚组（n = 332）。A‐PET阳性定义为Centiloid>；24。Tau阳性(T)是通过MK - 6240和Flortaucipir SUVR值在CU A‐个体锚定的至少一个Braak区域超过平均值+2SD来确定的，然后在A‐/T+病例中进行视觉确认。在PART （A‐/T+）组、A‐/T‐组和A+/T+组之间评估生物标志物的一致性。采用线性回归比较A/T组血浆GFAP、p - tau217、NFL水平和Centiloids。结果共发现25例（5.8%）患者被至少一种tau示踪剂定义为a‐/T+（74±6.3岁，52%女性，17例CU， 3例MCI， 5例痴呆）。A‐/T+病例的检测因示踪剂不同而不同：MK‐6240(n = 20), Flortaucipir(n = 16)（图1A）。在A‐/T+个体中，MK‐6240鉴定出13例CU、4例MCI和3例痴呆病例，而Flortaucipir鉴定出11例CU、3例MCI和2例痴呆病例（图1B）。在A‐/T+病例中，MK‐6240和Flortaucipir的一致性较低（n = 11,44%）（图1C）。A‐/T+个体与A‐/T‐没有显著的生物标志物差异，但生物标志物水平低于A‐/T+: Centiloids （MK‐6240:T=15.08, p <0.001; Flortaucipir: T=14.36, p <0.001）、GFAP （MK‐6240:T=5.04, p < 0.01; Flortaucipir: T=2.92, p <0.001）、p‐tau217 (MK‐6240:T=7.77, p <0.001; Flortaucipir: T=6.34, p <0.001)，但NFL （MK‐6240:T=1.35, p = 0.18; Flortaucipir: T=1.14, p = 0.25）除外（图2）。具有代表性的A和tau生物标志物病例（图3A），以及仅通过一种示踪剂分类为T+的不一致病例（图3B）。我们的初步分析显示，MK - 6240的a‐/T+病例发生率高于Flortaucipir，示踪剂之间的一致性较低，与a‐/T+相比，a‐/T+的生物标志物水平始终较低。需要更大规模的研究和纵向分析来确定具有不同tau生物标志物谱的A‐/T+个体的病理轨迹。
{"title":"PART characterization using MK-6240 and Flortaucipir","authors":"Carolina Soares, Emma Ruppert, Pamela C.L. Ferreira, Marina Scop Madeiros, Andreia Rocha, Matheus Scarpatto Rodrigues, Bruna Bellaver, Markley Silva Oliveira Jr., Guilherme Povala, Livia Amaral, Firoza Z Lussier, Joseph C. Masdeu, Dana L Tudorascu, Thomas K Karikari, David N. Soleimani-Meigooni, Juan Fortea, Val J Lowe, Hwamee Oh, Belen Pascual, Brian A. Gordon, Pedro Rosa-Neto, Suzanne L. Baker, Tharick A Pascoal","doi":"10.1002/alz70856_106723","DOIUrl":"10.1002/alz70856_106723","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Older adults with brain tau pathology but no evident amyloid-beta (A) pathology can be referred to as primary age-related tauopathy (PART). However, in vivo characterization of PART using biomarkers remains unclear, varying based on the method used to define tau pathology (e.g. different tau-PET tracers). Here, we conducted a head-to-head characterization of PART using two different tau-PET tracers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>We studied 433 individuals from the HEAD cohort (244 CU, 138 MCI, and 51 with dementia). Participants underwent clinical assessments, MRI, A-PET, both MK-6240 and Flortaucipir scans, and a subset with plasma biomarkers (<i>n</i> = 332). A-PET positivity was defined as Centiloid>24. Tau-positivity(T) was determined by MK-6240 and Flortaucipir SUVR values exceeding the mean+2SD in at least one Braak region anchored in CU A- individuals followed by visual confirmation in A-/T+ cases. Concordance across biomarkers was assessed among PART (A-/T+), A-/T- and A+/T+ groups. Plasma GFAP, <i>p</i>-tau217, NFL levels, and Centiloids were compared across A/T groups using linear regression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>We found a total of 25 (5.8 %) cases classified as A-/T+ defined by at least one tau tracer (74±6.3 years, 52% females, 17 CU, 3 MCI, 5 with dementia). Detection of A-/T+ cases varied by tracer: MK-6240(<i>n</i> = 20), Flortaucipir(<i>n</i> = 16) (Figure 1A). Among A-/T+ individuals, MK-6240 identified 13 CU, 4 MCI, and 3 dementia cases, while Flortaucipir identified 11 CU, 3 MCI, and 2 dementia cases(Figure 1B). Concordance between MK-6240 and Flortaucipir in A-/T+ cases was low (<i>n</i> = 11, 44%)(Figure 1C). A-/T+ individuals showed no significant biomarker differences from A-/T- but had lower biomarker levels than A+/T+: Centiloids (MK-6240: T=15.08, <i>p</i> <0.001; Flortaucipir: T=14.36, <i>p</i> <0.001), GFAP (MK-6240: T=5.04, <i>p</i> < 0.01; Flortaucipir: T=2.92, <i>p</i> <0.001), <i>p</i>-tau217 (MK-6240: T=7.77, <i>p</i> <0.001; Flortaucipir: T=6.34, <i>p</i> <0.001), except for NFL (MK-6240: T=1.35, <i>p</i> = 0.18; Flortaucipir: T=1.14, <i>p</i> = 0.25)(Figure 2). Representative A and tau biomarker cases (Figure 3A), along with discordant cases classified as T+ by only one tracer (Figure 3B), are illustrated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our preliminary analysis revealed a higher prevalence of A-/T+ cases with MK-6240 than Flortaucipir, low concordance between tracers and consistently lower biomark","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 S2","pages":""},"PeriodicalIF":11.1,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz70856_106723","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145955242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jakub Vávra, Wiebke Traichel, Andrea Benedet, Hanna Huber, Kaj Blennow, Laia Montoliu-Gaya, Nicholas Ashton, Henrik Zetterberg
<div> <section> <h3> Background</h3> <p>Conventional blood sampling for the testing of Alzheimer's disease (AD) biomarkers depends on stringent, time-sensitive, and temperature-dependent protocols for processing, shipping, and storage. Dry plasma spots (DPS) present a simpler, more scalable alternative for the collection, storage, and transport of blood samples and may offer an alternative sampling when access to blood volume is limited. Notably, neurodegenerative biomarkers such as <i>p</i>-tau, NfL, and GFAP from DPS have demonstrated a strong correlation with paired plasma on other platforms. In this pilot study, we aimed to expand on these findings by exploring a broader panel of central nervous system (CNS) biomarkers using DPS, assessing their potential for reliable and accurate detection.</p> </section> <section> <h3> Method</h3> <p>We used the NULISA™ platform to test multiplex detection of a CNS biomarker panel (127 proteins) in DPS and matched plasma, examining plasma–DPS correlations. A discovery cohort (<i>n</i> = 14; mean age 71.1 ± 12.8 years; 8 females [57%]) was selected from the Clinical Neurochemistry Laboratory in Mölndal, Sweden. DPS (Telimmune™ Plasma Separation Card) spiked with venous blood, were analysed with their paired EDTA plasma collected by traditional venipuncture. Pearson correlation was used to compare protein quantification across sample types.</p> </section> <section> <h3> Result</h3> <p>We demonstrated several biomarker associations between DPS and plasma with a correlation coefficient >0.99 and <i>p</i> <0.0001 (Figure 1), including APOe4 (<i>r</i> = 0.996), IL6 (<i>r</i> = 0.995), and FABP3 (<i>r</i> = 0.994). Notably, AD-related biomarkers like <i>p</i>-tau181 (r=0.89), <i>p</i>-tau231 (r=0.86), GFAP (r=0.8), NPTX2 (r=0.92), NFL (r=0.95), SMOC1 (r=0.91), and total Tau (r=0.93) all showed strong correlations and <i>p</i> <0.0001. DOPA decarboxylase, relevant for LBD and atypical Parkinsonian disorders, also correlated strongly (r=0.98, <i>p</i> <0.0001). VGF, a biomarker of synaptic plasticity altered in AD and Major Depressive Disorder showed a strong correlation (<i>r</i> = 0.95, <i>p</i> <0.0001). Among 16 interleukins, 11 had r>0.8 (<i>p</i> <0.0003) and 4 had r>0.5 (<i>p</i> <0.05), with IL6 (r=0.995) and IL12 (r=0.994) correlating notably strong (<i>p</i> <0.0001). However, 25% of proteins have a weak correlation coefficient of r<0.5 with plasma.</p> </section> <section> <h3> Conclusion</h3> <p>Our findings highlight the potential of DPS as a practical and scalable tool fo
{"title":"Multiplex Biomarker Detection in Dried Plasma Spots: finding the best biomarker for remote blood collection","authors":"Jakub Vávra, Wiebke Traichel, Andrea Benedet, Hanna Huber, Kaj Blennow, Laia Montoliu-Gaya, Nicholas Ashton, Henrik Zetterberg","doi":"10.1002/alz70856_106925","DOIUrl":"10.1002/alz70856_106925","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Conventional blood sampling for the testing of Alzheimer's disease (AD) biomarkers depends on stringent, time-sensitive, and temperature-dependent protocols for processing, shipping, and storage. Dry plasma spots (DPS) present a simpler, more scalable alternative for the collection, storage, and transport of blood samples and may offer an alternative sampling when access to blood volume is limited. Notably, neurodegenerative biomarkers such as <i>p</i>-tau, NfL, and GFAP from DPS have demonstrated a strong correlation with paired plasma on other platforms. In this pilot study, we aimed to expand on these findings by exploring a broader panel of central nervous system (CNS) biomarkers using DPS, assessing their potential for reliable and accurate detection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>We used the NULISA™ platform to test multiplex detection of a CNS biomarker panel (127 proteins) in DPS and matched plasma, examining plasma–DPS correlations. A discovery cohort (<i>n</i> = 14; mean age 71.1 ± 12.8 years; 8 females [57%]) was selected from the Clinical Neurochemistry Laboratory in Mölndal, Sweden. DPS (Telimmune™ Plasma Separation Card) spiked with venous blood, were analysed with their paired EDTA plasma collected by traditional venipuncture. Pearson correlation was used to compare protein quantification across sample types.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>We demonstrated several biomarker associations between DPS and plasma with a correlation coefficient >0.99 and <i>p</i> <0.0001 (Figure 1), including APOe4 (<i>r</i> = 0.996), IL6 (<i>r</i> = 0.995), and FABP3 (<i>r</i> = 0.994). Notably, AD-related biomarkers like <i>p</i>-tau181 (r=0.89), <i>p</i>-tau231 (r=0.86), GFAP (r=0.8), NPTX2 (r=0.92), NFL (r=0.95), SMOC1 (r=0.91), and total Tau (r=0.93) all showed strong correlations and <i>p</i> <0.0001. DOPA decarboxylase, relevant for LBD and atypical Parkinsonian disorders, also correlated strongly (r=0.98, <i>p</i> <0.0001). VGF, a biomarker of synaptic plasticity altered in AD and Major Depressive Disorder showed a strong correlation (<i>r</i> = 0.95, <i>p</i> <0.0001). Among 16 interleukins, 11 had r>0.8 (<i>p</i> <0.0003) and 4 had r>0.5 (<i>p</i> <0.05), with IL6 (r=0.995) and IL12 (r=0.994) correlating notably strong (<i>p</i> <0.0001). However, 25% of proteins have a weak correlation coefficient of r<0.5 with plasma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings highlight the potential of DPS as a practical and scalable tool fo","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 S2","pages":""},"PeriodicalIF":11.1,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz70856_106925","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145955245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matteo Carpi, Enrico Michele Salamone, Claudio Del Percio, Roberta Lizio, Susanna Lopez, Giuseppe Noce, Mina De Bartolo, Veronica Henao Isaza, Antonio Pio Afragola, Burcu Bölükbaş, Lorenc Barjami, Bahar Güntekin, Görsev Yener, Claudio Babiloni
<div> <section> <h3> Background</h3> <p>The periodic (e.g., EEG alpha power density) and aperiodic (offset and slope of EEG power density) components of resting-state EEG rhythms reflect different aspects of global neural dynamics and have been linked to excitatory/inhibitory balance. This study investigates these components across vigilance stages (wakefulness, flattening, ripples) in patients with mild cognitive impairment due to Alzheimer's disease (ADMCI) compared to healthy elderly (NOLD).</p> </section> <section> <h3> Method</h3> <p>Spectral analysis was performed on EEG data recorded from 19 scalp electrodes during a ∼30-minute session in age-, sex-, and education-matched ADMCI and NOLD participants (<i>n</i> = 17 vs. <i>n</i> = 11) showing transitions from quiet wakefulness (wakefulness stage, characterized by dominant posterior alpha activity at 8–12 Hz) to light sleep (flattening stage, marked by reduced EEG amplitude, and ripples stage, with diffuse theta activity at 4–7 Hz) based on a modified version of Hori's sleep onset classification. Periodic (spectral power in the 8–12 Hz alpha band for posterior electrodes) and aperiodic (offset and slope in the 3–40 Hz range) parameters were analyzed across vigilance stages. ANOVA was performed with Group, Stage, and Region of Interest (Frontal, Central, Temporal, Posterior) as factors.</p> </section> <section> <h3> Results</h3> <p>For the periodic EEG component, posterior alpha power density showed a significant Group effect, indicating reduced posterior alpha activity from quiet wakefulness to light sleep in ADMCI compared to NOLD (<i>p</i> < 0.01). In contrast, offset and exponent exhibited significant Condition effects, reflecting increased cortical inhibition (higher offset and exponent) across vigilance stages (<i>p</i> < 0.001) with no significant Group differences. Region of Interest effects showed greater inhibition across stages in parietal-occipital regions compared to anterior regions (<i>p</i> < 0.001).</p> </section> <section> <h3> Conclusion</h3> <p>In this study, periodic EEG alpha power was the most sensitive marker of vigilance dysfunctions in ADMCI, while aperiodic EEG parameters primarily captured a general increase in inhibition during transitions from wakefulness to light sleep, independent of disease. Vigilance-related changes in cortical inhibition do not appear to be a hallmark of prodromal Alzheimer's disease, which is instead characterized by altered oscillatory, frequency-specific activity. Future research should integrate both periodic and aperiodic EEG feat
静息状态脑电图节律的周期性（如脑电图α功率密度）和非周期性（脑电图功率密度偏移和斜率）成分反映了整体神经动力学的不同方面，并与兴奋/抑制平衡有关。本研究调查了由阿尔茨海默病（ADMCI）引起的轻度认知障碍患者与健康老年人（NOLD）在警觉性阶段（清醒、平坦、涟漪）的这些成分。方法对年龄、性别和教育程度相匹配的ADMCI和NOLD参与者（n = 17 vs. n = 11）在约30分钟的时段内从19个头皮电极记录的脑电图数据进行频谱分析，显示从安静清醒（清醒阶段，以8-12 Hz的主要后α活动为特征）到轻度睡眠（平坦阶段，以脑电图振幅降低为特征）和波纹阶段的转变。弥漫性θ波活动在4-7赫兹)，这是基于Hori睡眠开始分类的改进版本。周期性（后电极在8-12 Hz α波段的频谱功率）和非周期性（3-40 Hz范围内的偏移和斜率）参数在警戒阶段进行分析。以组、分期和感兴趣区域（额叶、中央、颞叶、后叶）为因素进行方差分析。结果对于周期性脑电成分，后路α功率密度呈现显著的组效应，表明与NOLD相比，ADMCI患者从安静清醒到浅睡眠的后路α活动减少（p < 0.01）。相比之下，抵消和指数表现出显著的条件效应，反映出皮层抑制在警觉性阶段增加（更高的抵消和指数）（p < 0.001），但组间差异不显著。与前区相比，兴趣区效应在顶枕区显示出更大的抑制作用（p < 0.001）。在这项研究中，周期性脑电图α功率是ADMCI中警觉性功能障碍最敏感的标志，而非周期性脑电图参数主要捕获了从清醒到浅睡眠过渡期间抑制的普遍增加，与疾病无关。警觉性相关的皮层抑制变化似乎不是前驱阿尔茨海默病的标志，相反，其特征是振荡性、频率特异性活动的改变。未来的研究应结合周期性和非周期性脑电图特征，以加强对阿尔茨海默病神经生理动力学的认识。
{"title":"Periodic and Aperiodic EEG Parameters During Transitions from Wakefulness to Light Sleep: Preliminary Results on Patients with Mild Cognitive Impairment Due to Alzheimer's Disease vs. Healthy Elderly","authors":"Matteo Carpi, Enrico Michele Salamone, Claudio Del Percio, Roberta Lizio, Susanna Lopez, Giuseppe Noce, Mina De Bartolo, Veronica Henao Isaza, Antonio Pio Afragola, Burcu Bölükbaş, Lorenc Barjami, Bahar Güntekin, Görsev Yener, Claudio Babiloni","doi":"10.1002/alz70856_106405","DOIUrl":"10.1002/alz70856_106405","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The periodic (e.g., EEG alpha power density) and aperiodic (offset and slope of EEG power density) components of resting-state EEG rhythms reflect different aspects of global neural dynamics and have been linked to excitatory/inhibitory balance. This study investigates these components across vigilance stages (wakefulness, flattening, ripples) in patients with mild cognitive impairment due to Alzheimer's disease (ADMCI) compared to healthy elderly (NOLD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>Spectral analysis was performed on EEG data recorded from 19 scalp electrodes during a ∼30-minute session in age-, sex-, and education-matched ADMCI and NOLD participants (<i>n</i> = 17 vs. <i>n</i> = 11) showing transitions from quiet wakefulness (wakefulness stage, characterized by dominant posterior alpha activity at 8–12 Hz) to light sleep (flattening stage, marked by reduced EEG amplitude, and ripples stage, with diffuse theta activity at 4–7 Hz) based on a modified version of Hori's sleep onset classification. Periodic (spectral power in the 8–12 Hz alpha band for posterior electrodes) and aperiodic (offset and slope in the 3–40 Hz range) parameters were analyzed across vigilance stages. ANOVA was performed with Group, Stage, and Region of Interest (Frontal, Central, Temporal, Posterior) as factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>For the periodic EEG component, posterior alpha power density showed a significant Group effect, indicating reduced posterior alpha activity from quiet wakefulness to light sleep in ADMCI compared to NOLD (<i>p</i> < 0.01). In contrast, offset and exponent exhibited significant Condition effects, reflecting increased cortical inhibition (higher offset and exponent) across vigilance stages (<i>p</i> < 0.001) with no significant Group differences. Region of Interest effects showed greater inhibition across stages in parietal-occipital regions compared to anterior regions (<i>p</i> < 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In this study, periodic EEG alpha power was the most sensitive marker of vigilance dysfunctions in ADMCI, while aperiodic EEG parameters primarily captured a general increase in inhibition during transitions from wakefulness to light sleep, independent of disease. Vigilance-related changes in cortical inhibition do not appear to be a hallmark of prodromal Alzheimer's disease, which is instead characterized by altered oscillatory, frequency-specific activity. Future research should integrate both periodic and aperiodic EEG feat","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 S2","pages":""},"PeriodicalIF":11.1,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz70856_106405","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145955178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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