Perceptual-phase eye-tracking during figure copying is associated with amyloid-β PET positivity in mild cognitive impairment

Abstract

Background

Amyloid-β (Aβ) pathology is a core feature of Alzheimer's disease (AD) and may be present in mild cognitive impairment (MCI). Accessible, non-invasive markers of early Aβ-related cognitive change are needed.

Objective

To investigate whether perceptual-phase eye-tracking metrics during figure copying are associated with Aβ-PET positivity in MCI.

Methods

In this cross-sectional study, 59 patients with MCI underwent ¹⁸F-flutemetamol PET and were classified as Aβ-PET positive (n = 34) or Aβ-PET negative (n = 25). Participants completed a simplified Rey-Osterrieth Complex Figure Test while wearing eye-tracking glasses. The display was then divided into perceptual and working areas of interest (AOIs), and metrics were extracted for each AOI. A matched-pair sensitivity analysis (n = 28) was performed to reduce differences in age, education, and Mini-Mental State Examination scores. Binary logistic regression was used to examine the association between Aβ-PET positivity and fixation duration in the perceptual AOI.

Results

The Aβ-PET positive group showed significantly longer fixation duration in the perceptual AOI (p = 0.027, r = 0.296), whereas no significant group differences were observed in the working AOI. Exploratory analyses showed higher fixation count, visit duration, visit count, and saccade count in the perceptual AOI of the Aβ-PET-positive group. Longer fixation duration in the perceptual AOI was independently associated with Aβ positivity (OR per second = 1.18, 95% CI 1.03–1.36, p = 0.021).

Conclusions

Aβ-PET positivity in MCI was associated with greater perceptual-phase gaze inefficiency during figure copying. Perceptual-phase eye-tracking metrics may serve as potential markers of amyloid-related visuospatial alteration in MCI.