Eye movement abnormalities as early biomarkers of Alzheimer’s disease

The diagnosis of Alzheimer's disease (AD) typically occurs after the onset of cognitive symptoms. Consequently, the global challenge around the world is to identify early and easily accessible biomarkers. Intriguingly, certain brainstem structures, such as the Superior Colliculus (SC), which plays a pivotal role in fixation maintenance and saccade programming, exhibit neurofibrillary changes sooner than cortical regions (Uematsu et al., 2018) and is susceptible to tau pathology and neuronal loss in AD patients. Accordingly, eye movement abnormalities associated with AD are often observed during structured laboratory tasks (Anderson and MacAskill, 2013). We hypothesized that subtle abnormalities may potentially be detectable even in the early stages of dementia (e.g., Mild Cognitive Impairment, MCI) during free-viewing tasks. We asked participants (N=90 AD, N=95 MCI patients and N=60 age-matched healthy controls) to freely explore a series of 20 real-world images presented on a computer screen while recording eye movements.

Free-viewing in AD was characterized by weaker gaze control, shorter saccades an hypersimplified visual exploration pattern. Alterations were also visible in MCI patients and

some oculomotor abnormalities were sensitive to amyloid-Beta positivity, thus suggesting the possibility to identify patients in the Alzheimer’s continuum.

In conclusion, spontaneous eye movement behavior can reveal subtle alterations in MCI and AD patients. Further research is needed to strengthen the link between oculomotor and standard biomarkers.