Circadian rhythms in neurodegenerative disorders

Nature Reviews Neurology, Journal Year: 2021, Volume and Issue: 18(1), P. 7 - 24

Published: Nov. 10, 2021

Language: Английский

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Defining circadian disruption in neurodegenerative disorders

Journal of Clinical Investigation, Journal Year: 2021, Volume and Issue: 131(19)

Published: Sept. 30, 2021

Neurodegenerative diseases encompass a large group of conditions that are clinically and pathologically diverse yet linked by shared pathology misfolded proteins. The accumulation insoluble aggregates is accompanied progressive loss vulnerable neurons. For some patients, the symptoms motor focused (ataxias), while others experience cognitive psychiatric (dementias). Among neurodegenerative disruption sleep/wake cycle occurs early in trajectory disease may be risk factor for development. In many cases, timing sleep other rhythmic physiological markers immediately raises possibility neurodegeneration-driven circadian system. aim this Review to summarize evidence supporting hypothesis core symptom within diseases, including Alzheimer's disease, Huntington's Parkinson's discuss latest progress field. discusses processes disrupt structure function system describes circadian-based interventions as well timed drug treatments improve wide range associated with disorders. It also identifies key gaps our knowledge.

Language: Английский

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Genetic variants affecting NQO1 protein levels impact the efficacy of idebenone treatment in Leber hereditary optic neuropathy

Cell Reports Medicine, Journal Year: 2024, Volume and Issue: 5(2), P. 101383 - 101383

Published: Jan. 24, 2024

Idebenone, the only approved treatment for Leber hereditary optic neuropathy (LHON), promotes recovery of visual function in up to 50% patients, but we can neither predict nor understand non-responders. Idebenone is reduced by cytosolic NAD(P)H oxidoreductase I (NQO1) and directly shuttles electrons respiratory complex III, bypassing affected LHON. We show here that two polymorphic variants drastically reduce NQO1 protein levels when homozygous or compound heterozygous. This hampers idebenone reduction. In its oxidized form, inhibits I, decreasing cells. By retrospectively analyzing a large cohort idebenone-treated LHON classified their response therapy, patients with heterozygous have poorest therapy response, particularly if carrying m.3460G>A/MT-ND1 mutation. These results suggest consideration patient genotype mitochondrial DNA mutation context therapy.

Language: Английский

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Chromatic pupillometry for evaluating melanopsin retinal ganglion cell function in Alzheimer’s disease and other neurodegenerative disorders: a review

Frontiers in Psychology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 8, 2024

The evaluation of pupillary light reflex (PLR) by chromatic pupillometry may provide a unique insight into specific photoreceptor functions. Chromatic refers to evaluating PLR different wavelengths and intensities in order differentiate outer/inner retinal contributions the PLR. Different protocols have been tested are now established assess in-vivo contribution mediated melanopsin ganglion cells (mRGCs). These intrinsically photosensitive photoreceptors modulate non-image-forming functions eye, which mainly circadian photoentrainment PLR, via projections hypothalamic suprachiasmatic olivary pretectal nucleus, respectively. In this context, has used as an alternative non-invasive tool evaluate mRGC system several clinical settings, including hereditary optic neuropathies, glaucoma, neurodegenerative disorders such Parkinson’s disease (PD), idiopathic/isolated rapid eye movement sleep behavior disorder (iRBD), Alzheimer’s (AD). purpose article is review key steps for studying mRGC-system functionality main findings technique research setting on neurodegeneration. mRGC-dependent responses short-wavelength sensitive, higher threshold activation, much slower sustained compared with rod- cone-mediated responses, driving tonic component during exposure high-irradiance continuous stimulus. Thus, mRGCs contribute post-illumination pupil response (PIPR) bright blue flash that persists after stimulation switched off. Given role photoentrainment, use perform functional mRGcs be proposed early biomarker mRGC-dysfunction characterized and/or dysfunction AD, PD, its prodromal phase iRBD. lay groundwork new, easily accessible can exploited also starting point future longitudinal cohort studies aimed at stratifying risk conversion these disorders.

Language: Английский

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Investigation of Pupillary Responses in Healthy Eyes and Eyes Implanted with Multifocal or Monofocal Intraocular Lenses

Current Eye Research, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 8

Published: Feb. 28, 2025

Purpose Comparison of dynamic pupillary parameters (DPPs) between healthy volunteers and multi- or monofocal intraocular lens (IOL) implanted eyes, examination the correlation postoperative visual acuity (VA), contrast sensitivity (CS), dysphotopsias (VD), these in IOL-implanted eyes.

Language: Английский

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Imaging Alzheimer’s Retinopathy

Published: Jan. 1, 2025

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Melanopsin retinal ganglion cell function in Alzheimer's vs. Parkinson's disease an exploratory meta-analysis and review of pupillometry protocols

Parkinsonism & Related Disorders, Journal Year: 2024, Volume and Issue: 123, P. 106063 - 106063

Published: Feb. 27, 2024

Language: Английский

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The Crosstalk Between Amyloid-β, Retina, and Sleep for the Early Diagnosis of Alzheimer’s Disease: A Narrative Review

Journal of Alzheimer s Disease Reports, Journal Year: 2024, Volume and Issue: 8(1), P. 1009 - 1021

Published: June 25, 2024

Alzheimer’s disease (AD) is the most common type of dementia, which characterised by progressive memory loss and accumulation hallmark markers amyloid-β (Aβ) neurofibrillary tangles in diseased brain. The current gold standard diagnostic methods have limitations being invasive, costly, not easily accessible. Thus, there a need for new avenues, such as imaging retina early AD diagnosis. Sleep disruption symptomatically frequent across preclinical subjects. As circadian activity, sleep-wake cycle, linked to retina, analysis their association may be useful additions achieving predictive In this narrative review, we provide an overview human studies concerning deposition Aβ, role sleep AD, gather evidence associations between sleep. Understanding mechanisms behind could assist interpretation retinal changes accurately AD.

Language: Английский

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Machine learning for comprehensive prediction of high risk for Alzheimer’s disease based on chromatic pupilloperimetry

Scientific Reports, Journal Year: 2022, Volume and Issue: 12(1)

Published: June 15, 2022

Abstract Currently there are no reliable biomarkers for early detection of Alzheimer's disease (AD) at the preclinical stage. This study assessed pupil light reflex (PLR) focal red and blue stimuli in central peripheral retina 125 cognitively normal middle age subjects (45–71 years old) high risk AD due to a family history (FH+), 61 age-similar with (FH−) using Chromatic Pupilloperimetry coupled Machine Learning (ML). All had ophthalmic assessment, retinal optic nerve thickness by optical coherence tomography. No significant differences were observed between groups cognitive function volumetric brain MRI. pupilloperimetry-based ML models highly discriminative differentiating without history, transient PLR (primarily cone-mediated), dim rod-mediated) stimuli. Features associated response latency (PRL) achieved Area Under Curve Receiver Operating Characteristic (AUC-ROC) 0.90 ± 0.051 (left-eye) 0.87 0.048 (right-eye). Parameters contraction arm rod cone-mediated more compared parameters relaxation melanopsin-mediated PLR. Significantly shorter PRL was measured FH+ group two test targets temporal visual field right eye that highest relative weight algorithm (mean standard error, SE 0.449 s 0.007 vs. 0.478 0.010 s, p = 0.038). Taken together our suggests subtle changes may be detected develop AD, decades before onset clinical symptoms. The dendrites melanopsin containing ganglion cells affected very stages AD.

Language: Английский

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

Annals of Clinical and Translational Neurology, Journal Year: 2023, Volume and Issue: 10(6), P. 918 - 932

Published: April 23, 2023

In Alzheimer's disease (AD), the presence of circadian dysfunction is well-known and may occur early in course. The melanopsin retinal ganglion cell (mRGC) system play a relevant role contributing to dysfunction. this study, we aimed at evaluating, through multimodal approach, mRGC AD an stage disease.We included 29 mild-moderate (70.9 ± 11 years) 26 (70.5 8 control subjects. We performed extensive neurophtalmological evaluation including optical coherence tomography with layer segmentation, actigraphic rest-activity rhythm, chromatic pupillometry analyzed new data-fitting brain functional MRI combined light stimuli assessing system.We demonstrated significant thinning infero-temporal sector compared controls. Moreover, documented by actigraphy circadian-impaired subgroup. Overall, measurements worsened age. Chromatic highlighted pupil-light response reduction rod condition pointing dendropathy. Finally, fMRI showed reduced occipital cortex activation blue particularly for sustained responses.Overall, results innovative approach clearly document dysfunctional stages as factor impairment providing also support use therapy AD.

Language: Английский

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