Alzheimer's Disease

There are over 55 million people worldwide living with dementia in 2020. This number will almost double every 20 years, reaching 78 million in 2030 and 139 million in 2050².  Eye tracking can help to make a non-invasive cognitive assessment and prediction of disease progression with Alzheimer’s Disease (AD) patients³. 

Oculomotor deficits in AD include saccade, fixation, and smooth pursuit⁴. Increased large intrusive saccades and less accurate saccadic movements of AD patients were found in saccadic tasks⁵. In fixation tasks, AD patients required a longer amount of time to fixate the target but had shorter fixation duration.

Studies have also shown that quantitative pupillometry may be able to detect Pupillary Light Reflex (PLR) changes in early Alzheimer’s disease^6,7,8. The majority of the studies have reported a faster pupillary redilation phase in AD patients compared to controls, making it the most consistent PLR feature in AD patients⁹. 

AD affects the cholinergic Edinger Westphal nucleus (EWN), which is the central brainstem sub-nucleus of the oculomotor complex, involved in the control of the pupil constriction. It has been suggested that pathological changes of the EWN may be an early and specific feature of AD and they may result in decreased cholinergic control of pupillary responses⁹.

Neuronal loss in the locus coeruleus of patients with AD may lead to decreased sympathetic supply to the iris and reduce the baseline pupil size⁹.

In AD, there is an increased latency of pupillary constriction to light, decreased constriction amplitude, reduced mean constriction velocity and faster redilation after light offset. Patients with AD typically display decreased maximum velocity of constriction (MCV) and maximum constriction acceleration (MCA) compared to controls, suggesting a parasympathetic deficiency. Amongst all pupillometric features, MCA and MCV have been reported as the most accurate parameters to differentiate AD patients from healthy controls⁹.

The use of PLR, as a measure of melanopsin Retinal Ganglion Cell function could also be of particular relevance for neurodegenerative disorders for which there is already evidence of circadian and sleep dysfunction¹⁰. Thus, PLR could be a promising biomarker for neurodegenerative diseases¹⁰.

1. Javaid FZ, Brenton J, Guo L, Cordeiro MF. Visual and Ocular Manifestations of Alzheimer's Disease and Their Use as Biomarkers for Diagnosis and Progression. Front Neurol. 2016;7:55. Published 2016 Apr 19. doi:10.3389/fneur.2016.00055

2. World Health Organization; 2021. Fact sheets of dementia. Available from: www.who.int/news-room/fact-sheets/detail/dementia. 

3. Tokushige SI, Matsumoto H, Matsuda SI, et al. Early detection of cognitive decline in Alzheimer's disease using eye tracking. Front Aging Neurosci. 2023;15:1123456. Published 2023 Mar 21. doi:10.3389/fnagi.2023.1123456
   
   
4. Tao L, Wang Q, Liu D, Wang J, Zhu Z, Feng L. Eye tracking metrics to screen and assess cognitive impairment in patients with neurological disorders. Neurol Sci Off J Ital Neurol Soc Ital Soc Clin Neurophysiol. 2020;41(7):1697-1704. doi:10.1007/s10072-020-04310-y
   
   
5. Noiret N, Carvalho N, Laurent É, et al. Saccadic Eye Movements and Attentional Control in Alzheimer's Disease. Arch Clin Neuropsychol. 2018;33(1):1-13. doi:10.1093/arclin/acx044
   
   
6. Bower MM, Sweidan AJ, Xu JC, Stern-Neze S, Yu W, Groysman LI. Quantitative Pupillometry in the Intensive Care Unit. J Intensive Care Med. 2021;36(4):383-391. doi:10.1177/0885066619881124
   
   
7. Granholm EL, Panizzon MS, Elman JA, et al. Pupillary Responses as a Biomarker of Early Risk for Alzheimer’s Disease. J Alzheimers Dis JAD. 2017;56(4):1419-1428. doi:10.3233/JAD-161078
   
   
8. Frost S, Robinson L, Rowe CC, et al. Evaluation of Cholinergic Deficiency in Preclinical Alzheimer’s Disease Using Pupillometry. J Ophthalmol. 2017;2017:7935406. doi:10.1155/2017/7935406
   
   
9. Chougule PS, Najjar RP, Finkelstein MT, Kandiah N, Milea D. Light-Induced Pupillary Responses in Alzheimer’s Disease. Front Neurol. 2019;10:360. doi:10.3389/fneur.2019.00360 
   
   
10. La Morgia C, Carelli V, Carbonelli M. Melanopsin Retinal Ganglion Cells and Pupil: Clinical Implications for Neuro-Ophthalmology. Front Neurol. 2018;9:1047. doi:10.3389/fneur.2018.01047