Hippocampal disconnection contributes to memory dysfunction in individuals at risk for Alzheimer's disease
Hippocampal disconnection contributes to memory dysfunction in individuals at risk for Alzheimer's disease
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DOI：
10.1073/pnas.0603414103
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发表时间：
2006-06-27
影响因子：
11.1
通讯作者：
Shah, Raj C.
中科院分区：
文献类型：
--
作者：
Stoub, Travis R.;deToledo-Morrell, Leyla;Shah, Raj C.
遗忘性轻度认知障碍（MCI）的概念描述了主要表现为记忆功能下降，但不符合痴呆症标准的老年人。因为这些人患阿尔茨海默病的风险很高，他们对了解疾病过程的前驱阶段非常感兴趣。MCI患者记忆功能障碍的机制尚不完全清楚。本研究采用定量、高分辨率结构MRI技术，在体内研究与轻度认知损伤相关的记忆功能障碍的解剖学基础。通过两种成像技术评估脑结构的变化：(i)全脑，基于体素的形态测定法，以确定白质体积减少的区域；(h)对内嗅皮层和海马的敏感体积分割，对记忆功能至关重要的灰质区域。在患有遗忘性轻度认知障碍的参与者中，与年龄匹配的对照组相比，结果显示海马旁回（包括穿孔路径）区域的白质体积显著减少。内嗅皮层和海马体也有明显萎缩。回归模型显示海马体积和海马旁白质体积是陈述性记忆表现的显著预测因子。这些结果表明，除了海马萎缩外，海马旁白质纤维的破坏还会部分切断海马与传入感觉信息的联系，从而导致老年MCI患者的记忆力下降。
The concept of amnestic mild cognitive impairment (MCI) describes older people who show a decline predominantly in memory function, but who do not meet criteria for dementia. Because such individuals are at high risk for developing Alzheimer's disease, they are of great interest for understanding the prodromal stages of the disease process. The mechanism underlying memory dysfunction in people with MCI is not fully understood. The present study uses quantitative, high-resolution structural MRI techniques to investigate, in vivo, the anatomical substrate of memory dysfunction associated with MCI. Changes in brain structures were assessed with two imaging techniques: (i) whole-brain, voxel-based morphometry to determine regions of reduced white matter volume and (h) sensitive volumetric segmentation of the entorhinal cortex and hippocampus, gray matter regions that are critically important for memory function. In participants with amnestic MCI, compared with age-matched controls, results showed a significant decrease in white matter volume in the region of the parahippocampal gyrus that includes the perforant path. There was also significant atrophy in both the entorhinal cortex and the hippocampus. Regression models demonstrated that both hippocampal volume and parahippocampal white matter volume were significant predictors of declarative memory performance. These results suggest that, in addition to hippocampal atrophy, disruption of parahippocampal white matter fibers contributes to memory decline in elderly individuals with MCI by partially disconnecting the hippocampus from incoming sensory information.