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.

Multimodal investigation of melanopsin retinal ganglion cells in Alzheimer's disease / La Morgia, C.; Mitolo, M.; Romagnoli, M.; Stanzani Maserati, M.; Evangelisti, S.; De Matteis, M.; Capellari, S.; Bianchini, C.; Testa, C.; Vandewalle, G.; Santoro, A.; Carbonelli, M.; D'Agati, P.; Filardi, M.; Avanzini, P.; Barboni, P.; Zenesini, C.; Baccari, F.; Liguori, R.; Tonon, C.; Lodi, R.; Carelli, V.. - In: ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY. - ISSN 2328-9503. - 10:6(2023), pp. 918-932. [10.1002/acn3.51773]

Multimodal investigation of melanopsin retinal ganglion cells in Alzheimer's disease

Mitolo M.;Romagnoli M.;Testa C.;
2023-01-01

Abstract

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.
2023
Multimodal investigation of melanopsin retinal ganglion cells in Alzheimer's disease / La Morgia, C.; Mitolo, M.; Romagnoli, M.; Stanzani Maserati, M.; Evangelisti, S.; De Matteis, M.; Capellari, S.; Bianchini, C.; Testa, C.; Vandewalle, G.; Santoro, A.; Carbonelli, M.; D'Agati, P.; Filardi, M.; Avanzini, P.; Barboni, P.; Zenesini, C.; Baccari, F.; Liguori, R.; Tonon, C.; Lodi, R.; Carelli, V.. - In: ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY. - ISSN 2328-9503. - 10:6(2023), pp. 918-932. [10.1002/acn3.51773]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2953232
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 2
  • ???jsp.display-item.citation.isi??? 2
social impact