Pupillary response test as a potential early diagnosis biomarker of Alzheimer’s disease

Abstract

Psychometric tests as the gold-standard for diagnosing Alzheimer’s disease (AD) tend to be inefficient, nonreproducible, and are affected by many factors. Research on pupillary response in AD is not novel; however, there has not been a single study providing the diagnostic value of pupillary response parameters as a recommendation for their potential use for early AD diagnosis. Objective: To investigate pupillary response parameters as clinical biomarkers of AD that are dynamic, affordable, efficient, and objective (non-operator dependent). Methods: A cross-sectional study on pupillary response parameters was conducted, with comparative and correlation-analytical tests between pupillary response and the Mini-Mental State Examination cognitive score. The diagnostic value of pupillary response parameters was obtained by determining the cutoff point of each parameter by calculating the sensitivity, specificity, Youden’s maximum index, Area Under the Curve (AUC) value from the Receiver Operating Characteristic (ROC) curve, positive predictive value, and negative predictive value. Pupillary response parameters were classified into four types: size, response time, velocity, and acceleration. Results: There were 128 respondents in total, consisting of cognitively-unimpaired young adults, cognitively-unimpaired older adults, and cognitively-impaired older adults. The pupillary response values without involving acceleration parameters were reliable. The diagnostic value of change in pupil size, the maximum and the average constriction velocity parameters have normal cognitive cutoff scores of 1.77 mm (sensitivity: 61.3%; specificity: 80%; positive predictive value [PPV]: 47.76%; negative predictive value [NPV]: 86.88%), ≥4.43 mm/s (sensitivity: 70.4%; specificity: 58.5%; PPV: 46.93%; NPV: 78.48%), and 3.12 mm/s (sensitivity: 70.4%; specificity: 55.0%; PPV: 45.83%; NPV: 77.5%), respectively. Conclusions: Pupillary response, in particular changes in constriction and velocity, can be potentially used as an early diagnostic biomarker for AD.