Left frontal hub connectivity delays cognitive impairment in autosomal-dominant and sporadic Alzheimer's disease.
Left frontal hub connectivity delays cognitive impairment in autosomal-dominant and sporadic Alzheimer's disease.
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DOI：
10.1093/brain/awy008
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发表时间：
2018-04-01
期刊：
影响因子：
--
通讯作者：
Ewers M
中科院分区：
文献类型：
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作者：
Franzmeier N;Düzel E;Jessen F;Buerger K;Levin J;Duering M;Dichgans M;Haass C;Suárez-Calvet M;Fagan AM;Paumier K;Benzinger T;Masters CL;Morris JC;Perneczky R;Janowitz D;Catak C;Wolfsgruber S;Wagner M;Teipel S;Kilimann I;Ramirez A;Rossor M;Jucker M;Chhatwal J;Spottke A;Boecker H;Brosseron F;Falkai P;Fliessbach K;Heneka MT;Laske C;Nestor P;Peters O;Fuentes M;Menne F;Priller J;Spruth EJ;Franke C;Schneider A;Kofler B;Westerteicher C;Speck O;Wiltfang J;Bartels C;Araque Caballero MÁ;Metzger C;Bittner D;Weiner M;Lee JH;Salloway S;Danek A;Goate A;Schofield PR;Bateman RJ;Ewers M
阿尔茨海默病中储备能力的神经基础尚未完全确定。Franzmeier等人表明，在常染色体显性显性和散发性阿尔茨海默病的早期阶段，额顶控制网络中更大的左额叶中枢连通性与更大的认知表现弹性有关。阿尔茨海默病患者在脑部病理存在的情况下维持认知能力的能力各不相同。一个主要的悬而未决的问题是，哪些大脑机制可能支持更高的储备能力，即在给定的阿尔茨海默病病理水平下相对较高的认知表现。高功能mri评估的左额叶皮质中枢的功能连接是潜在储备的核心候选脑机制，因为它与教育（即通常与高储备相关的保护因素）和减轻前驱阿尔茨海默病的认知障碍有关。然而，目前还没有研究评估左额叶皮层的这种中枢连通性是否支持阿尔茨海默病病理性大脑变化的整个进化过程，包括认知能力下降微妙的症状前阶段。为了解决这一研究空白，我们对74名常染色体显性阿尔茨海默病患者、55名显性遗传阿尔茨海默病网络的对照组、75名淀粉样蛋白阳性的老年受试者以及41名淀粉样蛋白阴性的认知正常老年受试者进行了横断静息状态功能MRI，这些受试者来自德国神经退行性疾病中心散发性阿尔茨海默病的生物标志物多中心研究。对于每个参与者，全局左额叶皮质连通性被计算为左额叶皮质（种子）和灰质中每个体素之间的平均静息状态功能连通性。作为疾病分期的标志，我们应用了常染色体显性遗传性阿尔茨海默病症状发作的估计年数和散发性阿尔茨海默病病例的脑脊液tau水平。在常染色体显性和散发性阿尔茨海默病患者中，较高水平的左额叶皮质连通性与较高的教育程度相关。对于常染色体显性阿尔茨海默病，发现了显著的左额叶皮质连通性×估计的发病相互作用年数，表明在高水平的连通性下，记忆和整体认知的下降速度较慢。同样，在散发性淀粉样蛋白阳性的老年受试者中，tau对认知的影响在左额叶皮层连接水平较高时减弱。多项式回归分析表明，认知能力下降的轨迹在阿尔茨海默病的晚期转移到左额叶皮质连接水平较高的患者。总之，我们的研究结果表明，在阿尔茨海默病的早期阶段，对认知障碍发展的抵抗力更高，至少部分归因于较高的左额叶皮质-中枢连通性。
The neural basis of reserve capacity in Alzheimer’s disease is yet to be fully determined. Franzmeier et al. show that greater left frontal hub connectivity within the fronto-parietal control network is associated with greater resilience of cognitive performance during the early stages of autosomal dominant and sporadic Alzheimer’s disease. Patients with Alzheimer’s disease vary in their ability to sustain cognitive abilities in the presence of brain pathology. A major open question is which brain mechanisms may support higher reserve capacity, i.e. relatively high cognitive performance at a given level of Alzheimer’s pathology. Higher functional MRI-assessed functional connectivity of a hub in the left frontal cortex is a core candidate brain mechanism underlying reserve as it is associated with education (i.e. a protective factor often associated with higher reserve) and attenuated cognitive impairment in prodromal Alzheimer’s disease. However, no study has yet assessed whether such hub connectivity of the left frontal cortex supports reserve throughout the evolution of pathological brain changes in Alzheimer’s disease, including the presymptomatic stage when cognitive decline is subtle. To address this research gap, we obtained cross-sectional resting state functional MRI in 74 participants with autosomal dominant Alzheimer’s disease, 55 controls from the Dominantly Inherited Alzheimer’s Network and 75 amyloid-positive elderly participants, as well as 41 amyloid-negative cognitively normal elderly subjects from the German Center of Neurodegenerative Diseases multicentre study on biomarkers in sporadic Alzheimer’s disease. For each participant, global left frontal cortex connectivity was computed as the average resting state functional connectivity between the left frontal cortex (seed) and each voxel in the grey matter. As a marker of disease stage, we applied estimated years from symptom onset in autosomal dominantly inherited Alzheimer’s disease and cerebrospinal fluid tau levels in sporadic Alzheimer’s disease cases. In both autosomal dominant and sporadic Alzheimer’s disease patients, higher levels of left frontal cortex connectivity were correlated with greater education. For autosomal dominant Alzheimer’s disease, a significant left frontal cortex connectivity × estimated years of onset interaction was found, indicating slower decline of memory and global cognition at higher levels of connectivity. Similarly, in sporadic amyloid-positive elderly subjects, the effect of tau on cognition was attenuated at higher levels of left frontal cortex connectivity. Polynomial regression analysis showed that the trajectory of cognitive decline was shifted towards a later stage of Alzheimer’s disease in patients with higher levels of left frontal cortex connectivity. Together, our findings suggest that higher resilience against the development of cognitive impairment throughout the early stages of Alzheimer’s disease is at least partially attributable to higher left frontal cortex-hub connectivity.
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影响因子：
5.3
作者：
Achard, S;Salvador, R;Bullmore, ET
通讯作者：
Bullmore, ET
影响因子：
9.9
作者：
Ewers, Michael;Insel, Philip S.;Weiner, Michael W.
通讯作者：
Weiner, Michael W.
DOI：
10.1093/brain/awu132
发表时间：
2014-08
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Crossley NA;Mechelli A;Scott J;Carletti F;Fox PT;McGuire P;Bullmore ET
通讯作者：
Bullmore ET
影响因子：
9.9
作者：
Chhatwal, Jasmeer P.;Schultz, Aaron P.;Sperling, Reisa A.
通讯作者：
Sperling, Reisa A.
影响因子：
4.8
作者：
Franzmeier N;Göttler J;Grimmer T;Drzezga A;Áraque-Caballero MA;Simon-Vermot L;Taylor ANW;Bürger K;Catak C;Janowitz D;Müller C;Duering M;Sorg C;Ewers M
通讯作者：
Ewers M