The 4 Mountains Test:a short test of spatial memory with high sensitivity for the diagnosis of pre-dementia Alzheimer’s disease

SHORT ABSTRACT: This article describes the 4 Mountains Test (4MT), a hippocampus-dependent test of working allocentric spatial memory. The hippocampus is affected early in Alzheimer’s disease (AD) and this article outlines the 4MT methodology and results of patient testing, which demonstrates the value of the 4MT in the diagnosis of pre-dementia AD. LONG 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 pre-dementia AD, which manifests clinically as mild cognitive impairment (MCI). The 4MT was applied to patients with mild cognitive impairment (MCI), stratified further based on cerebrospinal fluid 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. pre-dementia 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 pre-dementia AD.