Chan Dennis, Gallaher Laura Marie, Moodley Kuven, Minati Ludovico, Burgess Neil, Hartley Tom
Department of Clinical Neurosciences, University of Cambridge;
Clinical Imaging Sciences Centre, Brighton and Sussex Medical School.
J Vis Exp. 2016 Oct 13(116):54454. doi: 10.3791/54454.
This protocol describes the administration of the 4 Mountains Test (4MT), a short test of spatial memory, in which memory for the topographical layout of four mountains within a computer-generated landscape is tested using a delayed match-to-sample paradigm. Allocentric spatial memory is assessed by altering the viewpoint, colors and textures between the initially presented and target images. Allocentric spatial memory is a key function of the hippocampus, one of the earliest brain regions to be affected in Alzheimer's disease (AD) and impairment of hippocampal function predates the onset of dementia. It was hypothesized that performance on the 4MT would aid the diagnosis of predementia AD, which manifests clinically as Mild Cognitive Impairment (MCI). The 4MT was applied to patients with MCI, stratified further based on cerebrospinal fluid (CSF) AD biomarker status (10 MCI biomarker positive, 9 MCI biomarker negative), and with mild AD dementia, as well as healthy controls. Comparator tests included tests of episodic memory and attention widely accepted as sensitive measures of early AD. Behavioral data were correlated with quantitative MRI measures of the hippocampus, precuneus and posterior cingulate gyrus. 4MT scores were significantly different between the two MCI groups (p = 0.001), with a test score of ≤8/15 associated with 100% sensitivity and 78% specificity for the classification of MCI with positive AD biomarkers, i.e., predementia AD. 4MT test scores correlated with hippocampal volume (r = 0.42) and cortical thickness of the precuneus (r = 0.55). In conclusion, the 4MT is effective in identifying the early stages of AD. The short duration, easy application and scoring, and favorable psychometric properties of the 4MT fulfil the need for a simple but accurate diagnostic test for predementia AD.
本方案描述了四山测试（4MT）的实施方法，这是一种空间记忆的简短测试，其中使用延迟匹配样本范式测试对计算机生成景观中四座山的地形布局的记忆。通过改变最初呈现的图像和目标图像之间的视角、颜色和纹理来评估以自我为中心的空间记忆。以自我为中心的空间记忆是海马体的一项关键功能，海马体是阿尔茨海默病（AD）中最早受影响的脑区之一，海马体功能受损早于痴呆症发作。据推测，4MT的表现将有助于对临床症状为轻度认知障碍（MCI）的痴呆前期AD进行诊断。4MT应用于MCI患者，根据脑脊液（CSF）AD生物标志物状态进一步分层（10名MCI生物标志物阳性，9名MCI生物标志物阴性），以及轻度AD痴呆患者和健康对照者。对照测试包括广泛被认为是早期AD敏感指标的情景记忆和注意力测试。行为数据与海马体、楔前叶和后扣带回的定量MRI测量结果相关。两个MCI组之间的4MT分数有显著差异（p = 0.001），测试分数≤8/15对AD生物标志物阳性的MCI（即痴呆前期AD）分类的敏感性为100%，特异性为78%。4MT测试分数与海马体体积（r = 0.42）和楔前叶皮质厚度（r = 0.55）相关。总之，4MT在识别AD早期阶段有效。4MT的测试时间短、易于实施和评分，以及良好的心理测量特性满足了对痴呆前期AD进行简单而准确诊断测试的需求。
