melanopsin; Rod Opsins; Humans; Retina; Retinal Ganglion Cells; Alzheimer Disease/diagnostic imaging; Neuroscience (all); Neurology (clinical); General Neuroscience
Abstract :
[en] [en] OBJECTIVE: In Alzheimer's disease (AD), the presence of circadian dysfunction is well-known and may occur early in the disease course. The melanopsin retinal ganglion cell (mRGC) system may play a relevant role in contributing to circadian dysfunction. In this study, we aimed at evaluating, through a multimodal approach, the mRGC system in AD at an early stage of disease.
METHODS: We included 29 mild-moderate AD (70.9 ± 11 years) and 26 (70.5 ± 8 years) control subjects. We performed an extensive neurophtalmological evaluation including optical coherence tomography with ganglion cell layer segmentation, actigraphic evaluation of the rest-activity rhythm, chromatic pupillometry analyzed with a new data-fitting approach, and brain functional MRI combined with light stimuli assessing the mRGC system.
RESULTS: We demonstrated a significant thinning of the infero-temporal sector of the ganglion cell layer in AD compared to controls. Moreover, we documented by actigraphy the presence of a circadian-impaired AD subgroup. Overall, circadian measurements worsened by age. Chromatic pupillometry evaluation highlighted the presence of a pupil-light response reduction in the rod condition pointing to mRGC dendropathy. Finally, brain fMRI showed a reduced occipital cortex activation with blue light particularly for the sustained responses.
INTERPRETATION: Overall, the results of this multimodal innovative approach clearly document a dysfunctional mRGC system at early stages of disease as a relevant contributing factor for circadian impairment in AD providing also support to the use of light therapy in AD.
Research center :
CRC - Centre de Recherches du Cyclotron - ULiège [BE]
Disciplines :
Neurology
Author, co-author :
La Morgia, Chiara ; IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica, Bologna, Italy ; Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy ; IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy
Mitolo, Micaela; IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma Neuroimmagini Funzionali e Molecolari, Bologna, Italy ; Dipartimento di Medicina e Chirurgia, Università di Parma, Parma, Italy
Romagnoli, Martina ; IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy
Stanzani Maserati, Michelangelo; IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica, Bologna, Italy
Evangelisti, Stefania ; Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy
De Matteis, Maddalena; IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica, Bologna, Italy
Capellari, Sabina; IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica, Bologna, Italy ; Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy
Bianchini, Claudio; Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy
Testa, Claudia; IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma Neuroimmagini Funzionali e Molecolari, Bologna, Italy ; Dipartimento di Fisica ed Astronomia, Università di Bologna, Bologna, Italy
Vandewalle, Gilles ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Santoro, Aurelia; Dipartimento di Medicina Specialistica Diagnostica e Sperimentale, Università di Bologna, Bologna, Italy ; Alma Mater Research Institute on Global Challenges and Climate Change (Alma Climate), Università di Bologna, Bologna, Italy
Carbonelli, Michele; Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy
D'Agati, Pietro; IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica, Bologna, Italy
Filardi, Marco; Dipartimento di Medicina di Base, Neuroscienze e degli Organi di Senso, Università di Bari Aldo Moro, Bari, Italy ; Centro per le Malattie Neurodegenerative e l'Invecchiamento Cerebrale, Università di Bari Aldo Moro- A.O. Pia Fondazione Cardinale G. Panico, Tricase, Italy
Avanzini, Pietro; CNR, Istituto di Neuroscienze, Parma, Italy
Barboni, Piero; IRCCS San Raffaele, Milan, Italy
Zenesini, Corrado; IRCCS Istituto delle Scienze Neurologiche di Bologna, Unità di Epidemiologia e Statistica, Bologna, Italy
Baccari, Flavia; IRCCS Istituto delle Scienze Neurologiche di Bologna, Unità di Epidemiologia e Statistica, Bologna, Italy
Liguori, Rocco ; IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica, Bologna, Italy ; Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy
Tonon, Caterina; Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy ; IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma Neuroimmagini Funzionali e Molecolari, Bologna, Italy
Lodi, Raffaele; Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy ; IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma Neuroimmagini Funzionali e Molecolari, Bologna, Italy
Carelli, Valerio; Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy ; IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy
This work has been supported by the Italian Ministry of Health Young Researcher Project Grant (GR-2013-02358026 to CL). We are deeply grateful to patients and their caregivers for participating to the study. We also thank Prof. Piero Parchi for performing the CSF examination of the AD subjects included, Dr. Lidia Di Vito and Dr. Giulia Amore for their support in the initial evaluation of the patients, Prof. Gaetano Cantalupo and Dr. Jason Park for support in developing and setting the chromatic pupillometry protocol, Dr. Vincenzo Allegri for performing amyloid PET in AD patients, Prof. Claudio Franceschi for his support in the recruitment of centenarians, Dr. Maria Lunardelli and Dr. Maria Macchiarulo for the support in the recruitment of AD patients and Prof. Alfredo Sadun for his advice and fruitful discussions. This work has been also supported by Bibliosan. Open access funding provided by BIBLIOSAN.This work has been supported by the Italian Ministry of Health Young Researcher Project Grant (GR‐2013‐02358026 to CL). We are deeply grateful to patients and their caregivers for participating to the study. We also thank Prof. Piero Parchi for performing the CSF examination of the AD subjects included, Dr. Lidia Di Vito and Dr. Giulia Amore for their support in the initial evaluation of the patients, Prof. Gaetano Cantalupo and Dr. Jason Park for support in developing and setting the chromatic pupillometry protocol, Dr. Vincenzo Allegri for performing amyloid PET in AD patients, Prof. Claudio Franceschi for his support in the recruitment of centenarians, Dr. Maria Lunardelli and Dr. Maria Macchiarulo for the support in the recruitment of AD patients and Prof. Alfredo Sadun for his advice and fruitful discussions. This work has been also supported by Bibliosan. Open access funding provided by BIBLIOSAN.
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