Allocentric Spatial Memory Testing Predicts Conversion from Mild Cognitive Impairment to Dementia: An Initial Proof-of-Concept Study.
Allocentric Spatial Memory Testing Predicts Conversion from Mild Cognitive Impairment to Dementia: An Initial Proof-of-Concept Study.
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DOI：
10.3389/fneur.2016.00215
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发表时间：
2016
影响因子：
3.4
通讯作者：
Chan D
中科院分区：
文献类型：
--
作者：
Wood RA;Moodley KK;Lever C;Minati L;Chan D
海马是阿尔茨海默病（AD）中最先表现出神经退行性变的区域之一，因此了解其在异中心空间记忆中的作用可能有助于AD的早期诊断。4山测试（4 MT）是一种简短且易于管理的空间记忆测试，其基于源自啮齿动物单细胞和行为研究的海马功能的认知地图理论。在先前的横断面研究中，4 MT已被证明对AD引起的轻度认知障碍（MCI）具有敏感性和特异性。本报告描述了一项纵向研究的初步结果，该研究测试了一个假设，即非中心空间记忆是预测从MCI到痴呆症的转换。除了CSF淀粉样蛋白/tau生物标志物研究、体积MRI和神经心理学评估（包括Rey听觉语言学习测试（RAVLT）和连线测试“B”（TMT-B））外，15例MCI患者还接受了4 MT基线测试。在24个月时，9/15例患者转化为AD痴呆。4 MT预测转化为AD的准确率为93%（Cohen d = 2.52）。比较指标的预测准确性如下：CSF tau/β-淀粉样蛋白1 -42比值92%（d = 1.81），RAVLT 64%（d = 0.41），TMT-B 78%（d = 1.56）和海马体积77%（d = 0.65）。CSF tau水平与4 MT评分呈强负相关（r =-0.71）。这项概念验证研究为以下假设提供了初步支持：非中心空间记忆测试是痴呆前AD海马神经退行性变的预测性认知标志物。4 MT是一种简单、无创、直接的空间记忆测试，因此非常适合用于常规临床诊断实践。考虑到目前对早期AD的简单准确诊断测试的未满足需求以及潜在疾病改善治疗剂的持续开发，这一点特别重要，这些治疗剂在病程早期给药时可能更有效。通过将基于啮齿动物海马功能研究的测试应用于患者群体，这项工作代表了开发用于动物模型和人类受试者的早期AD海马参与的可翻译生物标志物的第一步。
The hippocampus is one of the first regions to exhibit neurodegeneration in Alzheimer’s disease (AD), and knowledge of its role in allocentric spatial memory may therefore aid early diagnosis of AD. The 4 Mountains Test (4MT) is a short and easily administered test of spatial memory based on the cognitive map theory of hippocampal function as derived from rodent single cell and behavioral studies. The 4MT has been shown in previous cross-sectional studies to be sensitive and specific for mild cognitive impairment (MCI) due to AD. This report describes the initial results of a longitudinal study testing the hypothesis that allocentric spatial memory is predictive of conversion from MCI to dementia. Fifteen patients with MCI underwent baseline testing on the 4MT in addition to CSF amyloid/tau biomarker studies, volumetric MRI and neuropsychological assessment including the Rey Auditory Verbal Learning Test (RAVLT) and Trail Making Test “B” (TMT-B). At 24 months, 9/15 patients had converted to AD dementia. The 4MT predicted conversion to AD with 93% accuracy (Cohen’s d = 2.52). The predictive accuracies of the comparator measures were as follows: CSF tau/β-amyloid1–42 ratio 92% (d = 1.81), RAVLT 64% (d = 0.41), TMT-B 78% (d = 1.56), and hippocampal volume 77% (d = 0.65). CSF tau levels were strongly negatively correlated with 4MT scores (r = −0.71). This proof-of-concept study provides initial support for the hypothesis that allocentric spatial memory testing is a predictive cognitive marker of hippocampal neurodegeneration in pre-dementia AD. The 4MT is a brief, non-invasive, straightforward spatial memory test and is therefore ideally suited for use in routine clinical diagnostic practice. This is of particular importance given the current unmet need for simple accurate diagnostic tests for early AD and the ongoing development of potential disease-modifying therapeutic agents, which may be more efficacious when given earlier in the disease course. By applying a test based on studies of hippocampal function in rodents to patient populations, this work represents the first step in the development of translatable biomarkers of hippocampal involvement in early AD for use in both animal models and human subjects.
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影响因子：
9.9
作者：
Deipolyi, A. R.;Rankin, K. P.;Gorno-Tempini, M. L.
通讯作者：
Gorno-Tempini, M. L.
影响因子：
29
作者：
Donohue, Michael C.;Sperling, Reisa A.;Salmon, David P.;Rentz, Dorene M.;Raman, Rema;Thomas, Ronald G.;Weiner, Michael;Aisen, Paul S.
通讯作者：
Aisen, Paul S.
DOI：
10.3233/jad-150855
发表时间：
2016-02-09
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Allison SL;Fagan AM;Morris JC;Head D
通讯作者：
Head D
影响因子：
4.2
作者：
Ewers M;Walsh C;Trojanowski JQ;Shaw LM;Petersen RC;Jack CR Jr;Feldman HH;Bokde AL;Alexander GE;Scheltens P;Vellas B;Dubois B;Weiner M;Hampel H;North American Alzheimer's Disease Neuroimaging Initiative (ADNI)
通讯作者：
North American Alzheimer's Disease Neuroimaging Initiative (ADNI)
影响因子：
--
作者：
Gomar, Jesus J.;Bobes-Bascaran, Maria T.;Goldberg, Terry E.
通讯作者：
Goldberg, Terry E.