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Multimodal evaluation of the melanopsin retinal ganglion cells system in relation to circadian rhythms in Alzheimer’s disease and aging
Author(s) -
La Morgia Chiara,
Mitolo Micaela,
Santoro Aurelia,
Romagnoli Martina,
Maserati Michelangelo Stanzani,
Evangelisti Stefania,
De Matteis Maddalena,
Palombo Flavia,
Bacalini Maria Giulia,
Capellari Sabina,
Carbonelli Michele,
Park Jason C.,
Liguori Rocco,
To Caterina,
Lodi Raffaele,
Carelli Valerio
Publication year - 2021
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.052286
Subject(s) - circadian rhythm , melanopsin , neurodegeneration , actigraphy , neuroscience , per1 , medicine , circadian clock , clock , endocrinology , biology , retina , disease , photopigment
Background Melanopsin retinal ganglion cells (mRGCs) are deputed to circadian photoentrainment and pupillary light reflex (PLR) regulations. Circadian dysfunction is reported in Alzheimer’s disease (AD) and contributes to dementia. Single‐Nucleotide‐Polymorphisms (SNPs) in clock genes have been associated to AD. Method We included 29 mild‐moderate AD and 26 matched controls performing neuroophthalmological evaluation including optical coherence tomography (OCT), actigraphic recordings of rest‐activity rhythms, chromatic pupillometry and brain functional MRI (fMRI) with light stimulation. 84 clock genes were analyzed by NGS and relevant SNPs validated in a larger cohort of AD (n=449) and controls (n=326). Result In AD disease duration was 3.9±2.8 years and MMSEc score 20.2±4.2. OCT showed a significant reduction of the infero‐temporal GCL thickness (p=0.036) in AD. Actigraphy did not disclose significant differences for circadian parameters (IS, IV, RA). However, a subgroup of “circadian‐impaired” AD was evident, and most of circadian parameters declined with aging. Pupillometry revealed a significant reduction of PLR peak amplitude in the rod protocol (p=0.006) significantly correlating with aging in AD. Brain fMRI documented the absence of significant responses in AD with sustained blue light stimulation at difference with controls. Genetic analysis in extended AD and control cohorts showed a significant association of the rs30127178 SNP in PER1 gene with AD. Conclusion These results demonstrate, by innovative multi‐modal approach, that mRGC system in AD is affected by neurodegeneration. This can be envisaged as a possible biomarker also for conversion from MCI to AD with potential implication for light therapy as a counteracting measure for dementia.