The 4 Mountains Test: A Short Test of Spatial Memory with High Sensitivity for the Diagnosis of Pre-dementia Alzheimer's Disease

Abstract

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.

Refining understanding of working memory buffers through the construct of binding: Evidence from a single case informs theory and clinical practise

“…Interestingly, the score of patient KA at the “4 mountains test” (8/15) exactly replicated an earlier finding with that task in patient Jon, and also fits with the cut-off score of 8 or below for differentiating between Mild Cognitive Impairment patients with or without positive CSF biomarkers for AD pathology (i.e., levels of β-amyloid 1-42 and phosphorylated tau) (Chan et al., 2016). This confirms that WM relational binding function is very sensitive to hippocampal damage, either arising from early hypoxia as in patient KA, or from AD-related pathology at the hippocampal stage, or simply from ageing.…”

Neurochemical correlates of scene processing in the precuneus/posterior cingulate cortex: a multimodal fMRI and 1H-MRS study

“…Much of our knowledge of the role of PCu/PCC in scene-related cognition is based on measurements tied to neuronal activity, including blood-oxygenation-level dependent (BOLD) functional magnetic resonance imaging (fMRI) in humans [Bzdok et al, 2015;Spreng et al, 2009] and single unit recording studies in both humans [Fox et al, 2018] and non-human primates [Dean, 2006;Sato et al, 2010]. Further evidence comes from neuropsychological investigations of scene-based processing following brain lesions [Futamura et al, 2018;Suzuki et al, 1998], including Alzheimer disease-linked neurodegeneration [Chan et al, 2016;Irish et al, 2015]. One avenue that remains substantially unexplored is the neuro-biochemical factors underpinning PCu/PCC activity during 4 complex scene cognition.…”

Allocentric Spatial Memory Testing Predicts Conversion from Mild Cognitive Impairment to Dementia: An Initial Proof-of-Concept Study

“…The 4MT is specifically designed to be resistant to non-spatial strategies (30). The 4MT can be applied in paper form, with or as an iPad app, and requires little in the way of tester training or instructions (a video example of test administration is viewable via the open access article by Chan et al (31)). The brevity of the test (around 10 minutes for the paper version and around 8 minutes for the app) is comparable to the MMSE (Mini Mental State Examination Test) (5), which is widely used worldwide as a short screening test for cognitive impairment but a poor predictor of progression from MCI to dementia (6).…”