Pupillary light response and sleep-wake activity in preclinical Alzheimer’s disease

Abstract

Purpose : Patients with Alzheimer’s disease (AD) demonstrate a significant loss of melanopsin-expressing retinal ganglion cells (mRGCs), which may contribute to sleep-wake disturbances. We performed a prospective case-control study in preclinical AD patients and controls to measure changes in pupillary light response and circadian rhythm, to reflect mRGC function.

Methods : We compared 5 patients with preclinical AD (identified with abnormal Ab 42 or Tau proteins on cerebrospinal fluid analysis) versus 5 normal aging controls (n = 10). Pupillary light response (PLR), indicative of mRGC function, was examined using intensity matched red and blue stimuli after 10 minutes of dark adaptation. A subset of participants wore a non-invasive wrist actigraphy device to quantify sleep efficiency and motor activity. All participants had thorough neuro-ophthalmic and neuropsychiatric assessments, including standardized sleep questionnaires.

Results : Pupillary light constriction was observed with both the red and blue stimuli, suggesting cone contribution and preserved mRGC function, respectively. For all participants, the PLR response was more sustained in the blue condition, which selectively activates mRGCs, compared with the red condition. Preclinical AD patients demonstrated differences in response to the two stimuli that may be greater than responses in controls. Wrist actigraphy profiles showed variable sleep-wake patterns and no statistically significant difference in sleep efficiency or subjective sleepiness between groups.

Conclusions : Changes in pupillary function and circadian disruption in preclinical AD patients were not observed. Chromatic pupillometry using intense blue stimuli to measure mRGC function is a non-invasive test that can be paired with wrist actigraphy and may be used as a marker for pre-clinical AD.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.