期刊
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
卷 10, 期 6, 页码 918-932出版社
WILEY
DOI: 10.1002/acn3.51773
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This study aimed to evaluate the melanopsin retinal ganglion cell (mRGC) system in early stages of Alzheimer's disease (AD) using a multi-modal approach. The results showed dysfunction of the mRGC system in AD patients, which may contribute to circadian impairment.
Objective: In Alzheimer's disease (AD), the presence of circadian dysfunction is well-known and may occur early in the disease course. The melanopsin reti-nal ganglion cell (mRGC) system may play a relevant role in contributing to circadian dysfunction. In this study, we aimed at evaluating, through a multi-modal approach, the mRGC system in AD at an early stage of disease. Methods: We included 29 mild-moderate AD (70.9 111 years) and 26 (70.5 18 years) control subjects. We performed an extensive neurophtalmolo-gical 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 gan-glion cell layer in AD compared to controls. Moreover, we documented by acti-graphy 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. Interpreta-tion: Overall, the results of this multimodal innovative approach clearly docu-ment 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.
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