NeuroTrax Science Team and Glen M. Doniger, PhD

The eyes have long been described as a window to the brain, but advances in neurometrics are elucidating the linkage between ocular health and cognitive function. Structural and functional measurements of the visual system can provide valuable insights into brain integrity, particularly when paired with objective cognitive assessment. Research using NeuroTrax digital cognitive assessment demonstrates that combining cognitive performance with ocular biomarkers offers clinicians a more complete understanding of neurological health and factors affecting everyday mental acuity (1,2).

Among the best examples comes from optical coherence tomography (OCT), a non-invasive imaging technique that measures retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness. Because retinal neurons are a direct extension of the central nervous system, changes within these structures often mirror neurodegenerative processes occurring in the brain (1).

Studies have shown significant associations between NeuroTrax global cognitive scores and RNFL thickness in people with multiple sclerosis (PwMS). Thinner RNFL measurements were tied to lower performance in attention and motor skills, and GCIPL thickness was strongly related to executive function, attention, and information processing speed (1). These findings suggest that retinal imaging is an early biomarker of cognitive decline that provides clinicians with objective structural evidence to complement cognitive assessment.

Beyond anatomy, efficiency of neural communication can be evaluated with visual evoked potentials (VEPs), which measure the time required for visual signals to travel from the retina to the visual cortex. Prolonged VEP latency reflects slower neural conduction and has been consistently associated with poorer performance in multiple NeuroTrax cognitive domains, including information processing speed, executive function, attention, and motor skills (3). Notably, VEP latency has been shown to predict cognitive performance better than visual acuity alone, highlighting its value as a key indicator of brain health (3).

Research has also demonstrated a relationship between delayed VEP latency and subjective cognitive fatigue. As neural communication efficiency declines, the brain appears to expend greater resources to maintain cognitive performance, contributing to the mental fatigue commonly experienced by individuals with neurological disease (4).

Clinical value is maximized when structural and functional ocular measures are interpreted alongside objective cognitive metrics. Combining OCT-derived retinal biomarkers with VEP latency and NeuroTrax cognitive indices explains substantially more variance in cognitive functioning than any single measure alone (2). This multimodal approach gives a comprehensive picture of nervous system health by capturing both structural integrity, neural conduction efficiency and cognitive profile.

Longitudinal studies demonstrate the predictive value of these biomarkers. Baseline VEP latency and inter-ocular latency have been shown to predict future changes in information processing speed over a two-year period, offering clinicians an opportunity to identify patients with heightened risk of cognitive decline before significant functional impairment develops (5).

Taken together, these findings reflect the concept of the "Mind's Eye." NeuroTrax objective cognitive assessment opens a window on the brain for OCT and VEP measurements, enabling a paradigm shift as clinicians move beyond isolated biomarkers toward an integrated picture of brain function. By evaluating how structural changes, neural signaling, and cognitive metrics interact, healthcare providers can improve monitoring, identify early neurological changes, and ultimately support more informed clinical decision-making.

References

[1] Dreyer-Alster, S., Gal, A., and Achiron, A. (2022). Optical coherence tomography is associated with cognitive impairment in multiple sclerosis. Journal of Neuro-Ophthalmology, 42(1), e14–e21. DOI: 10.1097/WNO.0000000000001326

[2] Covey, T.J., Golan, D., Sergott, R., Wilken, J., Zarif, M., Bumstead, B., Buhse, M., Kaczmarek, O., Doniger, G.M., Penner, I.K., Hancock, L.M., Bogaardt, H., Barrera, M.A., Morrow, S.A., Galetta, S., and Gudesblatt, M. (2024). Peering further into the mind’s eye: Combining visual evoked potential and optical coherence tomography measures enhances insight into the variance in cognitive functioning in multiple sclerosis. Journal of Neurology, 271(2), 658–673. DOI: 10.1007/s00415-023-12075-5

[3] Covey, T.J., Golan, D., Doniger, G.M., Sergott, R., Zarif, M., Srinivasan, J., Bumstead, B., Wilken, J., Buhse, M., Mebrahtu, S., and Gudesblatt, M. (2021). Visual evoked potential latency predicts cognitive function in people with multiple sclerosis. Journal of Neurology, 268(11), 4311–4320. DOI: 10.1007/s00415-021-10561-2

[4] Covey, T.J., Golan, D., Doniger, G.M., Sergott, R., Zarif, M., Bumstead, B., Buhse, M., Kaczmarek, O., Mebrahtu, S., Bergmann, C., Wilken, J., and Gudesblatt, M. (2022). The relationship between cognitive impairment, cognitive fatigue, and visual evoked potential latency in people with multiple sclerosis. Multiple Sclerosis and Related Disorders, 57:103349. DOI: 10.1016/j.msard.2021.103349

[5] Covey, T.J., Golan, D., Doniger, G.M., Sergott, R., Zarif, M., Bumstead, B., Buhse, M., Kaczmarek, O., Mebrahtu, S., Bergmann, C., Wilken, J., and Gudesblatt, M. (2022). Longitudinal assessment of the relationship between evoked potentials and cognitive performance in multiple sclerosis. Clinical Neurophysiology, 137, 66–74. DOI: 10.1016/j.clinph.2022.02.013