VisMET: a passive, efficient, and sensitive assessment of visuospatial memory in healthy aging, mild cognitive impairment, and Alzheimer's disease

Abstract

The entorhinal-hippocampal circuit is one of the earliest sites of cortical pathology in Alzheimer's disease (AD). Visuospatial memory paradigms that are mediated by the entorhinal-hippocampal circuit may offer a means to detect memory impairment during the early stages of AD. In this study, we developed a 4-min visuospatial memory paradigm called VisMET (Visuospatial Memory Eye-Tracking Task) that passively assesses memory using eye movements rather than explicit memory judgements. We had 296 control or memory-impaired participants view a set of images followed by a modified version of the images with either an object removed, or a new object added. Healthy controls spent significantly more time viewing these manipulations compared to subjects with mild cognitive impairment and AD. Using a logistic regression model, the amount of time that individuals viewed these manipulations could predict cognitive impairment and disease status with an out of sample area under the receiver-operator characteristic curve of 0.85. Based on these results, VisMET offers a passive, sensitive, and efficient memory paradigm capable of detecting objective memory impairment and predicting cognitive and disease status.

Figure 1.

Visual exploration of later removed objects during the encoding phase. (A) Participants viewed images during the encoding phase containing an object that was removed in the future during the recognition phase as indicated by the yellow critical region. (B) Healthy controls, MCI, and AD participants fixated on ∼90% of the subsequently removed objects. The MCI group viewed the same percentage of critical regions as healthy controls (P > 0.05, unpaired t-test), whereas the AD group viewed slightly fewer critical regions than healthy controls (P < 0.001, unpaired t-test). (C) Healthy, MCI, and AD participants all spent roughly 30% of the time viewing the critical regions, with no significant differences across groups. (***) 0.001.

Figure 2.

Age-related changes in VisMET performance. (A) Younger participants (50–60) viewed more of the critical regions containing removed objects compared to older participants (60–70, 70+). (B) Younger participants (50–60) spent a greater percentage of viewing time in the critical regions containing the removed object compared to older participants (60–70, 70+). (C) For comparison, memory scores on the free recall portion of the FCSRT are shown. Asterisks in each panel indicate significant differences in performance as shown: (*) 0.05, (**) 0.01, (***) 0.001; unpaired t-test.

Figure 3.

Visuospatial Memory Eye-Tracking Test (VisMET). Participants were asked to view a set of images for 5 sec with a 1 sec interstimulus interval each during the encoding phase. During the recognition phase, participants viewed the same set of images with either one item removed (removed condition) or one item added (added condition). The manipulated regions used to quantify memory performance are indicated by the yellow box, which was not visible during viewing. The final test parameters consisted of the presentation of two sets of 10 original-manipulated pairs (seven with removed condition and three with added condition) with a delay of 1 min in between the original and manipulated presentations. The entire task took 4 min.

Figure 4.

VisMET performance in mild cognitive impairment and Alzheimer's disease. Participants viewed images with either an object removed (A) or added (D) as indicated by the yellow critical regions, which was invisible to the viewer. (B) Subjects with MCI and AD showed impaired visuospatial memory performance (removed condition) compared to controls. (C) Control subjects viewed a greater percentage of the critical regions compared to AD participants regardless of the extent of difficulty between the original and manipulated presentations. The less difficult images better distinguished healthy and MCI individuals. Asterisks indicate significant differences in performance between healthy controls and MCI: (*) 0.05, (**) 0.01, (***) 0.001, (****) 0.0001; unpaired t-test). (E) Memory performance for the added condition was impaired (i.e., less time viewing the added object) in the MCI and AD populations compared to controls. (F) Manipulated images with high difficulty showed the most significant differences in performance between healthy and MCI participants as indicated by the asterisks. Viewing times for any of the added objects did not exceed 50% and as a result, difficulty could not be measured at higher viewing times.

Figure 5.

VisMET performance predicts cognitive impairment and disease status. (A) Viewing of the removed and added objects during the recognition phase could accurately predict performance on the Montreal Cognitive Assessment (MoCA ≤ 23 or MoCA > 23), a standard measure of cognitive impairment. (B) Viewing of the removed and added objects could separate those clinically diagnosed with MCI/AD from healthy controls. (C) Memory performance was visualized on a two-dimensional plane representing performance. Most MCI/AD participants fell within the lower left quadrant of the plane indicating below average performance for both the added and removed condition. Healthy participants within this quadrant exhibited a memory profile indicative of AD.