Reduction of Basal Forebrain Cholinergic System Parallels Cognitive Impairment in Patients at High Risk of Developing Alzheimer's Disease
Reduction of Basal Forebrain Cholinergic System Parallels Cognitive Impairment in Patients at High Risk of Developing Alzheimer's Disease
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DOI：
10.1093/cercor/bhp232
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发表时间：
2010-07-01
期刊：
影响因子：
3.7
通讯作者：
Cantero, Jose L.
中科院分区：
文献类型：
--
作者：
Grothe, Michel;Zaborszky, Laszlo;Cantero, Jose L.
神经病理学研究表明，基底前脑胆碱能系统（BFCS）在阿尔茨海默病（AD）中受到影响，但没有体内证据表明该系统在AD高危受试者中的早期损伤。在这里，我们发现，轻度认知障碍（MCI）患者表现出显着的体积减少的核基底的Meynert（NbM）使用最近开发的概率地图的BFCS空间。此外，在已知受AD影响的区域中，不同大细胞区室的体积随着区域灰质萎缩而显著变化，并且被发现与MCI患者的认知能力下降相关。双侧Broca斜角带水平核（Ch3）和额叶减少（内侧额回、眶回、胼胝体下回、前扣带回和额中回）与认知状态的整体下降显著相关，而Ch4后室（NbM）和颞叶的体积减少（包括海马，内嗅皮层和杏仁核）与MCI患者延迟回忆受损相关。这些发现首次建立了BFCS特定胆碱能隔室变性与AD高危受试者认知相关缺陷之间的联系。
Neuropathological studies suggest that the basal forebrain cholinergic system (BFCS) is affected in Alzheimer's disease (AD), but there is no in vivo evidence of early damage to this system in subjects at high risk of developing AD. Here, we found that mild cognitive impairment (MCI) patients exhibited significant volume reduction of the nucleus basalis of Meynert (NbM) using recently developed probabilistic maps of the BFCS space. In addition, volumes of different magnocellular compartments varied significantly with regional gray matter atrophy in regions known to be affected by AD and were found to correlate with cognitive decline in MCI patients. Bilateral reductions of the horizontal nucleus of the diagonal band of Broca (Ch3) and frontal lobe (medial frontal, orbital, subcallosal gyrus, anterior cingulate, and middle frontal gyrus) were significantly associated with a global decline in cognitive status, whereas volume reduction of the posterior compartment of Ch4 (NbM) and temporal lobe (including hippocampus, entorhinal cortex, and amygdala) were associated with impaired delayed recall in MCI patients. These findings establish, for the first time, a link between degeneration of specific cholinergic compartments of the BFCS and cognitive-related deficits in subjects at high risk of developing AD.