Neurobiology of Aging最新文献_第4页

Independent associations of sleep and physical activity with cognition are mediated by hippocampal microstructure in middle-aged and older adults 中老年人海马微结构介导了睡眠和体力活动与认知的独立关联。

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2024-12-05 DOI: 10.1016/j.neurobiolaging.2024.11.011

Daniel D. Callow , Adam P. Spira , Vadim Zipunnikov , Corinne Pettigrew , Andreia Faria , Sarah K. Wanigatunga , Marilyn Albert , Arnold Bakker , Anja Soldan , the BIOCARD Research Team

Sleep and physical activity levels are both associated with cognitive performance among older adults; however, the brain mechanisms underlying these beneficial relationships remain poorly understood. This study investigated cross-sectional associations of actigraphic estimates of physical activity and sleep with cognition and diffusion imaging-based measures of medial temporal lobe (MTL) gray matter microstructural integrity in adults free of dementia. Participants were 132 older adults from the Biomarkers of Cognitive Decline Among Normal Individuals (BIOCARD) cohort study (119 cognitively unimpaired and 13 with mild cognitive impairment; mean age=70.8 years). Multiple linear regression analyses assessed the relationships between total volume of physical activity (TVPA), total sleep time (TST), and sleep efficiency (SE) with cognitive performance and MTL microstructural integrity. Results indicated that greater TVPA and SE were both independently associated with higher hippocampal and parahippocampal microstructure integrity (indicated by lower mean diffusivity) and better visuospatial processing abilities, independent of the volume of these structures and of amyloid burden, measured by positron emission tomography. Additionally, higher hippocampal microstructure statistically mediated the independent associations of physical activity and sleep with visuospatial abilities, independent of MTL volume and Aβ load. These findings suggest that physical activity and sleep are independently associated with cognitive performance, and that hippocampal microstructural integrity may be an underlying mechanism supporting these associations.

老年人的睡眠和体力活动水平都与认知能力有关；然而，这些有益关系背后的大脑机制仍然知之甚少。本研究调查了身体活动和睡眠的活动图估计与基于认知和弥散成像的内侧颞叶灰质微结构完整性测量在无痴呆成年人中的横断面关联。参与者是来自正常个体认知衰退生物标志物（BIOCARD）队列研究的132名老年人(119名认知未受损，13名轻度认知障碍；平均年龄=70.8岁)。多元线性回归分析评估了身体活动总量（TVPA）、总睡眠时间（TST）和睡眠效率（SE）与认知表现和MTL微观结构完整性之间的关系。结果表明，较高的TVPA和SE与较高的海马和海马旁微观结构完整性（通过较低的平均扩散率表示）和较好的视觉空间处理能力独立相关，与正电子发射断层扫描测量的这些结构和淀粉样蛋白负荷的体积无关。此外，较高的海马微结构在统计学上介导了身体活动和睡眠与视觉空间能力的独立关联，而与MTL体积和Aβ负荷无关。这些发现表明，身体活动和睡眠与认知表现独立相关，海马体微结构完整性可能是支持这些关联的潜在机制。

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引用次数: 0

Mismatch negativity predicts age-related declines in memory precision 错配消极预示着与年龄相关的记忆精度下降。

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2024-12-04 DOI: 10.1016/j.neurobiolaging.2024.11.012

Ricky Chow , Stevenson Baker , Shimin Mo , Jennifer A. Bugos , Claude Alain , R. Shayna Rosenbaum

Does precision in auditory perception predict precision in subsequent memory (i.e., mnemonic discrimination) in aging? This study examined if the mismatch negativity (MMN), an electrophysiological marker of change detection and encoding, relates to age differences in mnemonic discrimination. The MMN was recorded in 92 adults (18–86 years, 47 females) in a passive oddball paradigm using tone sequences. Participants then completed a surprise recognition test for presented sequences (i.e., old targets) against novel sequences (i.e., similar lures and dissimilar foils). Across the adult lifespan, MMN amplitudes showed attenuation with increasing age, accompanied by worse performance discriminating targets from lures and foils. Across participants, smaller MMN amplitude predicted worse recognition performance. Notably, MMN amplitude partially explained age-related declines in target-lure discriminability, but not target-foil discriminability. Findings reinforce the MMN as a marker of mnemonic discrimination, and clarify how age-related declines in memory precision at retrieval may be explained by age differences at encoding.

听觉感知的准确性是否预示着衰老过程中后续记忆（即助记辨别）的准确性？本研究考察了错配负性（MMN），一种变化检测和编码的电生理标记，是否与记忆辨别的年龄差异有关。在被动古怪模式下使用声调序列记录92名成年人（18-86岁，47名女性）的MMN。然后，参与者完成了对呈现序列（即旧目标）和新序列（即相似的诱饵和不同的箔）的惊喜识别测试。在整个成年期，MMN振幅随年龄的增长而衰减，同时区分诱饵和箔的目标性能变差。在所有参与者中，MMN振幅越小，识别能力越差。值得注意的是，MMN振幅部分解释了与年龄相关的目标-诱饵辨别能力下降，但不能解释目标-箔辨别能力下降。研究结果加强了MMN作为助记辨别的标志，并阐明了在检索时记忆精度的年龄相关下降如何可以用编码的年龄差异来解释。

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引用次数: 0

Relationships of functional connectivity of motor cortex, primary somatosensory cortex, and cerebellum to balance performance in middle-aged and older adults 中老年人运动皮质、初级体感皮质和小脑功能连通性与平衡表现的关系。

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2024-11-29 DOI: 10.1016/j.neurobiolaging.2024.11.009

Ashwini Sansare , Thamires N.C. Magalhaes , Jessica A. Bernard

Connectivity of somatosensory cortex (S1) and cerebellum with the motor cortex (M1) is critical for balance control. While both S1-M1 and cerebellar-M1 connections are affected with aging, the implications of altered connectivity for balance control are not known. We investigated the relationship between S1-M1 and cerebellar-M1 connectivity and standing balance in middle-aged and older adults. Our secondary objective was to investigate how cognition affected the relationship between connectivity and balance. Our results show that greater S1-M1 and cerebellar-M1 connectivity was related to greater postural sway during standing. This may be indicative of an increase in functional recruitment of additional brain networks to maintain upright balance despite differences in network connectivity. Also, cognition moderated the relationship between S1-M1 connectivity and balance, such that those with lower cognition had a stronger relationship between connectivity and balance performance. It may be that individuals with poor cognition need increased recruitment of brain regions (compensation for cognitive declines) and in turn, higher wiring costs, which would be associated with increased functional connectivity.

体感皮质（S1）和小脑与运动皮质（M1）的连通性对平衡控制至关重要。虽然S1-M1和小脑- m1连接都随着年龄的增长而受到影响，但连接改变对平衡控制的影响尚不清楚。我们研究了中老年人S1-M1与小脑- m1连通性和站立平衡之间的关系。我们的第二个目标是研究认知如何影响连通性和平衡之间的关系。我们的研究结果表明，更大的S1-M1和小脑- m1连接与站立时更大的姿势摇摆有关。这可能表明，尽管网络连接存在差异，但维持直立平衡的额外脑网络的功能招募有所增加。认知调节了S1-M1连通性与平衡之间的关系，认知水平较低的人连通性与平衡表现之间的关系较强。这可能是认知能力差的个体需要增加大脑区域的招募（对认知能力下降的补偿），反过来，更高的布线成本，这将与功能连接的增加有关。

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引用次数: 0

Locus coeruleus MRI contrast, cerebral perfusion, and plasma Alzheimer’s disease biomarkers in older adults 老年人蓝斑核磁共振对比、脑灌注和血浆阿尔茨海默病生物标志物

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2024-11-27 DOI: 10.1016/j.neurobiolaging.2024.11.008

Shubir Dutt , Shelby L. Bachman , Martin J. Dahl , Yanrong Li , Belinda Yew , Jung Yun Jang , Jean K. Ho , Kaoru Nashiro , Jungwon Min , Hyun Joo Yoo , Aimée Gaubert , Amy Nguyen , Anna E. Blanken , Isabel J. Sible , Anisa J. Marshall , Arunima Kapoor , John Paul M. Alitin , Kim Hoang , Jeremy Rouanet , Lorena Sordo , Daniel A. Nation

The locus coeruleus (LC) is among the first brain structures impacted by Alzheimer’s disease (AD), and noradrenergic denervation may contribute to early neurovascular dysfunction in AD. Mechanistic links between the LC and cerebral perfusion have been demonstrated in rodents, but there have been no similar studies in aging humans. Community-dwelling older adults with no history of stroke or dementia (N=66) underwent structural (T1-MPRAGE; T1-FSE) and perfusion (resting pCASL) MRI. Plasma AD biomarkers levels were evaluated for Aβ42/40 ratio (n=56) and pTau181 (n=60). Higher rostral LC structural MRI contrast was associated with lower perfusion in entorhinal and limbic regions but higher perfusion in lateral and medial orbitofrontal cortices. Relationships between LC structure and regional cerebral perfusion were attenuated in older adults with higher plasma pTau levels and lower plasma Aβ42/40 ratios. Previously unstudied links between LC structure and cerebral perfusion are detectible in older adults using MRI and are attenuated in those showing greater AD pathophysiologic change, suggesting an uncoupling of LC-cerebral perfusion relationships in older adults with aggregating AD-related pathophysiology.

蓝斑（LC）是最早受阿尔茨海默病（AD）影响的脑结构之一，去甲肾上腺素能去神经支配可能有助于AD早期神经血管功能障碍。LC与脑灌注之间的机制联系已在啮齿动物中得到证实，但尚未在衰老的人类中进行类似的研究。无卒中或痴呆病史的社区老年人（N=66）接受了结构性(T1-MPRAGE；T1-FSE)和灌注（静息pCASL） MRI。测定血浆AD生物标志物Aβ42/40比值（n=56）和pTau181 （n=60）。高吻侧LC结构MRI对比与鼻内区和边缘区灌注较低相关，但眶额外侧和内侧皮质灌注较高。在血浆pTau水平较高、血浆Aβ42/40比值较低的老年人中，LC结构与局部脑灌注的关系减弱。以前未研究的LC结构和脑灌注之间的联系在老年人中可以通过MRI检测到，并且在表现出较大AD病理生理变化的老年人中被减弱，这表明老年人LC-脑灌注关系与AD相关病理生理的聚合不耦合。

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引用次数: 0

Hippocampal atrophy over two years in relation to tau, amyloid-β and memory in older adults 老年人两岁以上海马萎缩与tau蛋白、淀粉样蛋白β和记忆的关系

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2024-11-23 DOI: 10.1016/j.neurobiolaging.2024.11.007

Etienne Aumont , Marc-André Bedard , Aurélie Bussy , Jaime Fernandez Arias , Cecile Tissot , Brandon J. Hall , Joseph Therriault , Nesrine Rahmouni , Jenna Stevenson , Stijn Servaes , Arthur C. Macedo , Paolo Vitali , Nina Margherita Poltronetti , Olga Fliaguine , Lydia Trudel , Serge Gauthier , Mallar M. Chakravarty , Pedro Rosa-Neto

In this longitudinal brain imaging study, we aimed to characterize hippocampal tau accumulation and subfield atrophy relative to cortical amyloid-β and memory performance. We measured tau-PET in regions associated with Braak stages I to VI, global amyloid-PET burden, hippocampal subfield volumes and memory assessments from 173 participants aged 55–85. Eighty-six of these participants were tested again two years later. Tau-PET change in the Braak II region, corresponding to the hippocampus and the entorhinal cortex, was significantly associated with the cornu ammonis 1 (CA1) atrophy and memory score. This CA1 atrophy did not significantly mediate the association between tau and memory, nor did global amyloid-PET burden correlate with tau-PET changes in the Braak II region. Longitudinal hippocampal tau accumulation is amyloid-β-independent and co-localized with subfield atrophy. As tau-associated memory decline seems to be independent from hippocampal atrophy, other mechanisms could contribute to the deficit.

在这项纵向脑成像研究中，我们旨在表征海马tau积累和亚场萎缩与皮层淀粉样蛋白-β和记忆表现的关系。我们测量了Braak期I至VI期相关区域的tau-PET，全球淀粉样蛋白- pet负荷，海马体亚区体积和173名55-85岁参与者的记忆评估。其中86名参与者在两年后再次接受了测试。海马和内嗅皮质对应的Braak II区Tau-PET变化与羊角氨1 （CA1）萎缩和记忆评分显著相关。这种CA1萎缩并没有显著介导tau蛋白和记忆之间的关联，也没有整体淀粉样蛋白- pet负荷与Braak II区tau- pet变化相关。海马纵向tau积累与淀粉样蛋白β无关，并与亚场萎缩共定位。由于tau相关的记忆衰退似乎与海马体萎缩无关，其他机制可能导致这种缺陷。

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引用次数: 0

Cerebral white matter hyperintensity volumes: Normative age- and sex-specific values from 15 population-based cohorts comprising 14,876 individuals 大脑白质高密度体积：来自 15 个人群队列（包括 14 876 人）的年龄和性别标准值

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2024-11-20 DOI: 10.1016/j.neurobiolaging.2024.11.006

Floor A.S. de Kort , Elisabeth J. Vinke , Ewoud J. van der Lelij , Devasuda Anblagan , Mark E. Bastin , Alexa Beiser , Henry Brodaty , Nishi Chaturvedi , Bastian Cheng , Simon R. Cox , Charles DeCarli , Christian Enzinger , Evan Fletcher , Richard Frayne , Marius de Groot , Felicia Huang , M. Arfan Ikram , Jiyang Jiang , Bonnie Y.K. Lam , Pauline Maillard , J. Matthijs Biesbroek

White matter hyperintensities (WMH) increase with age, with marked interindividual variation. There is a need for normative data by age and sex, to improve individualized WMH burden assessment. In this study, we pooled cross-sectional data from 15 population-based cohorts (14,876 nondemented individuals, age 18–97 years), through the Meta VCI Map consortium. Whole brain and tract-specific MRI-assessed WMH volumes were calculated in MNI-152 space. We used quantile regression to create centile curves of WMH volume versus age, stratified by sex. Total WMH volume and interindividual variance increased exponentially with age for both sexes, with females showing higher WMH volumes. WMH volume increase with aging was not uniform across the white matter, but instead followed one of three different patterns depending on location. Age- and sex-specific normative data for total and regional WMH volumes were created. Our study provides detailed information on the normal distribution of total and regional WMH volumes across adulthood. The normative data enable a quantitative approach to interpreting total and regional WMH volumes in clinical practice and research settings.

白质高密度（WMH）会随着年龄的增长而增加，但个体间差异明显。我们需要按年龄和性别划分的常模数据，以改进个体化的 WMH 负担评估。在这项研究中，我们通过 Meta VCI 地图联盟汇集了来自 15 个人群队列（14876 名非痴呆患者，年龄在 18-97 岁之间）的横断面数据。在 MNI-152 空间中计算了全脑和特定磁共振成像评估的 WMH 体积。我们使用量子回归法绘制了 WMH 体积与年龄的百分位曲线，并按性别进行了分层。男性和女性的WMH总体积和个体间差异均随年龄呈指数增长，女性的WMH体积更大。随着年龄的增长，白质中WMH体积的增加并不一致，而是根据位置的不同而呈现三种不同的模式。我们创建了总体积和区域 WMH 体积的年龄和性别特异性标准数据。我们的研究提供了成年期总体积和区域 WMH 体积正常分布的详细信息。有了这些标准数据，就可以在临床实践和研究环境中采用定量方法来解释总体积和区域 WMH 体积。

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引用次数: 0

Lifespan longitudinal changes in mesocortical thickness and executive function: Role of dopaminergic genetic predisposition 中皮层厚度和执行功能的寿命纵向变化：多巴胺能遗传易感性的作用

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2024-11-20 DOI: 10.1016/j.neurobiolaging.2024.11.005

Giuseppe G. Miranda, Chen Gonen, Jessica N. Kraft, Karen M. Rodrigue, Kristen M. Kennedy

Dopamine (DA) signaling is critical for optimal cognitive aging, especially in prefrontal-parietal and fronto-striatal networks. Single nucleotide polymorphisms associated with dopamine regulation, COMTVal158Met and DRD2C957T, stand to exert influence on executive function performance via neural properties. The current study investigated whether longitudinal thinning of mesocortical regions is related to COMT and DRD2 genetic predisposition and associated with decline in executive function over four-years. N=235 healthy adults aged 20–94 years were recruited, with n=124 returning 4-years later. Latent mixed effects modeling revealed dopamine-related thinning in several frontal, parietal, and cingulate regions as well as decline in verbal fluency category switching across 4-years. Mesocortical thinning was also related to switching performance. Greater cortical thinning interacted with DA-genotype risk for lower DA-availability to predict poorer switching performance in parietal and posterior cingulate cortex. These findings lend support to the notion that early-life factors, such as genetic influence on neurotransmitter function, play a role in cognitive and brain aging and their linked association.

多巴胺（DA）信号对于最佳认知衰老至关重要，特别是在前额叶-顶叶和额纹状体网络中。与多巴胺调控相关的单核苷酸多态性COMTVal158Met和DRD2C957T可能通过神经特性对执行功能表现产生影响。目前的研究调查了中皮质区域的纵向变薄是否与COMT和DRD2遗传易感性有关，并与四年来执行功能的下降有关。N=235名年龄在20-94岁的健康成年人被招募，N= 124名4年后返回。潜在混合效应模型显示，在4年的时间里，大脑额叶、顶叶和扣带区域的多巴胺相关变薄，以及语言流利程度类别转换的下降。中皮层变薄也与切换性能有关。更大的皮质变薄与低da可用性的da基因型风险相互作用，预测顶叶和后扣带皮层较差的转换性能。这些发现支持了这样一种观点，即早期生活因素，如遗传对神经递质功能的影响，在认知和大脑衰老及其相关关系中发挥作用。

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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

Neurobiology of Aging

Pub Date : 2024-11-19 DOI: 10.1016/S0197-4580(24)00190-8

引用次数: 0

Effects of age and dietary methionine restriction on cognitive and behavioural phenotypes in the rTg4510 mouse model of frontotemporal dementia 年龄和饮食蛋氨酸限制对 rTg4510 小鼠额颞叶痴呆模型认知和行为表型的影响。

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2024-11-14 DOI: 10.1016/j.neurobiolaging.2024.11.004

Marina Souza Matos , Annesha Sil , Gernot Riedel , Bettina Platt , Mirela Delibegovic

Metabolic disorders such as diabetes and obesity are linked to neurodegenerative diseases, with evidence of lower brain glucose metabolism and insulin resistance in dementia patients. Dietary methionine restriction (MR) is a nutritional intervention that enhances insulin sensitivity and delays ageing-associated metabolic alterations, however, its impact on neurodegenerative diseases is not fully understood. Here, we examined the behavioural and metabolic phenotypes of a murine tauopathy model (rTg4510), which overexpresses human P301L mutated tau, at 6 and 12 months of age, assessing the impact of an 8-week dietary MR in the older group. While rTg4510 mice displayed progressive behavioural and motor impairments at both ages, MR led to significant benefits in the 12-month-old cohort, improving motor coordination, short-term memory, and social recognition. These effects were accompanied by increased glycolysis markers and FGF21R1 levels in the hippocampus, alongside unaltered glucose metabolism/adiposity. Overall, our results reveal the impact of MR on an FTD-mouse model, suggesting this as a potential therapeutic intervention to delay and/or improve the progression of tau-related disease.

糖尿病和肥胖等代谢紊乱与神经退行性疾病有关，有证据表明痴呆症患者的脑葡萄糖代谢和胰岛素抵抗较低。膳食蛋氨酸限制（MR）是一种营养干预措施，可增强胰岛素敏感性并延缓衰老相关的代谢改变，但其对神经退行性疾病的影响尚未完全明了。在这里，我们研究了过度表达人类 P301L 突变 tau 的小鼠 tau 病模型（rTg4510）在 6 个月和 12 个月大时的行为和代谢表型，并评估了为期 8 周的饮食 MR 对年长组小鼠的影响。虽然 rTg4510 小鼠在两个年龄段都表现出进行性行为和运动障碍，但 MR 在 12 个月大的小鼠群中产生了显著的益处，改善了运动协调、短期记忆和社会识别能力。这些影响伴随着海马中糖酵解标记物和 FGF21R1 水平的增加，以及葡萄糖代谢/肥胖的改变。总之，我们的研究结果揭示了MR对FTD小鼠模型的影响，表明这是一种潜在的治疗干预措施，可以延缓和/或改善tau相关疾病的进展。

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引用次数: 0

Cross-sectional and longitudinal relationships among blood-brain barrier disruption, Alzheimer's disease biomarkers, and cognition in cognitively normal older adults 认知正常的老年人血脑屏障破坏、阿尔茨海默病生物标志物和认知之间的横向和纵向关系。

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2024-11-14 DOI: 10.1016/j.neurobiolaging.2024.11.002

Marisa Denkinger , Suzanne Baker , Theresa M. Harrison , Trevor Chadwick , William J. Jagust

Blood-brain barrier disruption (BBBd) occurs in aging, particularly in regions vulnerable to Alzheimer’s disease (AD) pathology. However, its relationship to pathological protein accumulation, neurodegeneration, and cognitive impairment in normal aging is unclear. We used dynamic contrast-enhanced MRI (DCE-MRI) and positron emission tomography (PET) imaging in cognitively normal older adults to explore how BBBd correlates with brain atrophy and cognitive function, and whether these relationships are influenced by Aβ or tau. We found that greater BBBd in the hippocampus (HC) and an averaged BBBd-susceptible ROI were linked to worse episodic memory, with interactions between BBBd and atrophy influencing this relationship, independent of Aβ and tau. However, there were no significant relationships between BBBd and non-memory cognitive performance. In participants with longitudinal AD biomarker and cognitive data acquired prior to DCE-MRI, faster longitudinal entorhinal cortex (EC) tau accumulation and episodic memory decline were associated with greater HC BBBd, independent of global Aβ changes and regional atrophy. These findings enhance our understanding of the complex relationships between AD biomarkers, cognitive decline, and BBBd.

衰老过程中会出现血脑屏障破坏（BBBd），尤其是在易受阿尔茨海默病（AD）病理影响的区域。然而，它与正常衰老过程中的病理蛋白积累、神经变性和认知障碍之间的关系尚不清楚。我们使用动态对比增强核磁共振成像（DCE-MRI）和正电子发射断层扫描（PET）成像技术对认知功能正常的老年人进行了研究，以探讨 BBBd 与脑萎缩和认知功能的相关性，以及这些关系是否受 Aβ 或 tau 的影响。我们发现，海马（HC）中更大的 BBBd 和平均 BBBd 易感 ROI 与更差的外显记忆有关，BBBd 和萎缩之间的相互作用影响了这种关系，而与 Aβ 和 tau 无关。但是，BBBd与非记忆认知表现之间没有明显的关系。在DCE-MRI之前获得纵向AD生物标志物和认知数据的参与者中，纵向内侧皮层（EC）tau积累速度加快和情节记忆衰退与HC BBBd增大有关，这与全局Aβ变化和区域萎缩无关。这些发现加深了我们对AD生物标志物、认知能力下降和BBBd之间复杂关系的理解。

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引用次数: 0