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

The overall goal of this experiment is to determine whether the 4 Mountains Test is sensitive and specific for the earliest stages of Alzheimer's disease, prior to the onset of dementia, when patients have mild cognitive impairment. The hippocampal formation is a crucial part of the brain for memory. Decades of neuroscience research have shown that it represents the layout of the environment around us and our location within it.

We designed the 4 Mountains Test to assess this capability for using conditions that effect this part of the brain. The hippocampal formation is one of the first brain regions effected in Alzheimer's disease, and the aim of this study therefore was to determine whether the 4 Mountains Test is sensitive and specific for the earliest stages of Alzheimer's disease when patients present with mild cognitive impairment. The test is quick to administer, and performance is impaired in cases of hippocampal damage, even though each scene is tested after only a couple of seconds.

The test has been developed in paper form, as well as an iPad app, in which the self-contained instructions, and the use of a touch screen to record responses reduces test time. The paper version of this procedure will be demonstrated by myself, and the app version will be demonstrated by a PhD student, David Howett. Begin by seating a participant, who is not colorblind and has normal vision, in a quiet testing room.

Ensure that the participant wears glasses if required to correct their vision. Inform the participant that they will be shown a picture of a mountain landscape. Then, tell the participant about their response choices.

One of the four landscapes represents the same place as in the first image, however, this has been taken under a different viewpoint, and under different conditions of lighting and weather. The task for the participant is to determine which landscape represents the same place as in the first image. Then, have the participant complete the practice test, consisting of three examples.

Allow the participant to ask for clarification if they are unsure about any aspect of the task. Provide verbal feedback by drawing the participant's attention to relevant features within the picture. Once the participant has completed the practice examples, tell them that the next step is to complete the main test, which is consists of 15 total questions.

Inform the participant that they will see the stimulus image for eight seconds, and to have 20 seconds to choose each answer. Then, show the test items one at a time. Start timing once the first sample image is presented.

First, show the sample image for eight seconds. Turn to a blank page, and then show the response images for up to 20 seconds, or until the participant indicates their selection. The page turning allows a 2-second gap between the presentation of stimulus and response images.

Ask the participant to indicate their response by pointing to the selected image. Stop timing when the participant has made the selection. Record the participants response, and the time taken to make that response on the corresponding response sheet, giving no feedback on whether the response is correct or not.

Finally, calculate the score for the number of correct responses as a sum total. The app version of the 4 Mountains Test runs automatically once the 4 Mountains Test icon is touched. After the first few images are shown, show the participant three trial slides, and allow them to make responses by touching the screen.

As with the hard copy version, highlight any errors, and show the correct answer. Then, after the completion of the trial, have the participant begin the test. Finally, after the test has been completed, download the text file listing the final score, total test time, and the type of incorrect errors made.

There were significant differences in 4MT performance between the healthy controls and the MCI biomarker positive group, as well as between controls, and the group with mild AD dementia. Crucially, the 4MT is able to significantly differentiate between biomarker positive and the biomarker negative MCI patients with AD pathology. The MCI biomarker negative group had similar scores to the age-matched control group.

4MT place memory score correlated significantly with total hippocampal volume, and cortical thickness of the precuneus. Once mastered, this test can be applied in around 10 to 15 minutes for the hard copy version, and in around 10 minutes for the app version. While attempting this procedure, it's important to ensure that the instructions are understood fully by the participant.

Across different ages and cultures the task is easy to understand, because it simply involves asking the participant to judge whether they're looking at the same place. However, it's also challenging because each scene is comprised of the same elements seen from different points of view and under different lighting conditions. As a result of this work, the 4 Mountains Test is now being applied to thousands of asymptomatic older individuals who are at risk of developing Alzheimer's disease in order to determine whether spatial memory is impaired prior to the onset of symptoms.

The 4 Mountains Test can also be used as an outcome measure in clinical trials aimed at delaying progression for mild cognitive impairment to dementia, and also as a test for early Alzheimer's disease in different cultural settings.