Evidence map›Paper›PMID 31821378›Full record

ArticlePloS one2019

Pupillometry evaluation of melanopsin retinal ganglion cell function and sleep-wake activity in pre-symptomatic Alzheimer's disease.

Angela J Oh, Giulia Amore, William Sultan, Samuel Asanad, Jason C Park, Martina Romagnoli, Chiara La Morgia, Rustum Karanjia, Michael G Harrington, Alfredo A Sadun

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
1.9field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Ocular changes as potential biomarkers for early diagnosis of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Review
  8. Alzheimer's disease pathophysiology in the Retina.Progress in retinal and eye research · 2024
    Review
  9. Review
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Circadian rhythms in neurodegenerative disorders.Nature reviews. Neurology · 2022
    Review
  20. Defining circadian disruption in neurodegenerative disorders.The Journal of clinical investigation · 2021
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 5 institutions in 3 countries.

Angela J OhDoheny Eye institute, UCLA Stein Eye Institute, University of California, Los Angeles, Department of Ophthalmology, Los Angeles, California, United States of America.ORCID 0000-0002-3835-6702
Giulia AmoreDoheny Eye institute, UCLA Stein Eye Institute, University of California, Los Angeles, Department of Ophthalmology, Los Angeles, California, United States of America.
William SultanDoheny Eye institute, UCLA Stein Eye Institute, University of California, Los Angeles, Department of Ophthalmology, Los Angeles, California, United States of America.
Samuel AsanadDoheny Eye institute, UCLA Stein Eye Institute, University of California, Los Angeles, Department of Ophthalmology, Los Angeles, California, United States of America.
Jason C ParkColumbia University, Department of Psychology, New York, New York, United States of America.
Martina RomagnoliIRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica, Bologna, Italy.ORCID 0000-0003-1995-558X
Chiara La MorgiaIRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica, Bologna, Italy.
Rustum KaranjiaDoheny Eye institute, UCLA Stein Eye Institute, University of California, Los Angeles, Department of Ophthalmology, Los Angeles, California, United States of America.
Michael G HarringtonThe Huntington Medical Research Institutes and Molecular Neurology Program, Pasadena, California, United States of America.
Alfredo A SadunDoheny Eye institute, UCLA Stein Eye Institute, University of California, Los Angeles, Department of Ophthalmology, Los Angeles, California, United States of America.
University of California, Los Angeles · USIstituto delle Scienze Neurologiche di Bologna · ITColumbia University · USThe Huntington Library, Art Museum, and Botanical Gardens · USUniversity of Ottawa · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMelanopsin-expressing retinal ganglion cells (mRGCs), intrinsically photosensitive RGCs, mediate the light-based pupil response and the light entrainment of the body's circadian rhythms through their connection to the pretectal nucleus and hypothalamus, respectively. Increased awareness of circadian rhythm dysfunction in neurological conditions including Alzheimer's disease (AD), has led to a wave of research focusing on the role of mRGCs in these diseases. Postmortem retinal analyses in AD patients demonstrated a significant loss of mRGCs, and in vivo measurements of mRGC function with chromatic pupillometry may be a potential biomarker for early diagnosis and progression of AD.

methodsWe performed a prospective case-control study in 20 cognitively healthy study participants: 10 individuals with pre-symptomatic AD pathology (pre-AD), identified by the presence of abnormal levels of amyloid β42 and total Tau proteins in the cerebrospinal fluid, and 10 age-matched controls with normal CSF amyloid β42 and Tau levels. To evaluate mRGC function, we used a standardized protocol of chromatic pupillometry on a Ganzfeld system using red (640 nm) and blue (450 nm) light stimuli and measured the pupillary light response (PLR). Non-invasive wrist actigraphy and standardized sleep questionnaires were also completed to evaluate rest-activity circadian rhythm.

resultsOur results did not demonstrate a significant difference of the PLR between pre-AD and controls but showed a variability of the PLR in the pre-AD group compared with controls on chromatic pupillometry. Wrist actigraphy showed variable sleep-wake patterns and irregular circadian rhythms in the pre-AD group compared with controls.

conclusionsThe variability seen in measurements of mRGC function and sleep-wake cycle in the pre-AD group suggests that mRGC dysfunction occurs in the pre-symptomatic AD stages, preceding cognitive decline. Future longitudinal studies following progression of these participants can help in elucidating the relationship between mRGCs and circadian rhythm dysfunction in AD.

Indexed as

Circadian RhythmRod OpsinsSleepActigraphyAgedAged, 80 and overAlzheimer DiseaseCase-Control StudiesFemaleHumansMaleMelanopsinProspective StudiesPupilReflex, PupillaryRetinal Ganglion CellsMelanopsinRod Opsins

Identifiers

PMID31821378
PMCPMC6903762
OpenAlexW2995208088

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.