Changes in Retinal Multilayer Thickness and Vascular Network of Patients With Alzheimer’s Disease

Abstract Background: Retinal biomarkers of Alzheimer’s disease (AD) were largely investigated during last decades. Brain conditions could be reflected by retinal nervous and vascular parameters. It can be used to enhance the accuracy of early diagnosis of AD.Objective: Our study aimed to evaluate the difference of retinal neuro-layer thickness and vascular parameters between AD patients and health control (HC) subjects.Methods: Non-invasive technology of optical coherence tomography angiography (OCTA) were adopted to acquire the combination thickness of retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL), as well as the full retinal thickness (FRT). Vascular branch (VB), vascular curvature (VC), and vascular density (VD) were also collected in AD and HC groups. Mini-mental state examination (MMSE) was adopted to evaluate the cognitive levels of all subjects. After obtaining all the parameters, we used Mann-Whitney U test to compare the mean values of all retinal regions parameters between ADs and HCs. Pearson's correlation was used to test the association between retinal parameters and MMSE score, and vascular parameters.Results: Compared with HCs, the RNFL+GCL thickness of inferior quadrant, FRT of inferior and temporal quadrant, and retinal VD of patients with AD were significantly reduced (p < 0.05). The retinal thickness had significant correlations with MMSE scores (p < 0.05). Meanwhile, the retinal VD was significantly correlated with the average RNFL+GCL thickness (p < 0.05, r = 0.5956).Conclusion: In conclusion, our study suggested that AD patients had significant reduced RNFL+GCL thickness and vascular density compared with the age-matched HCs. Meanwhile, these reductions correlated with the cognitive level of the subjects. Trial registration number: ChiCTR2000035243Date of registration: Aug., 5, 2020URL of trial registry record: http://www.chictr.org.cn/index.aspx

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Changes in retinal multilayer thickness and vascular network of patients with Alzheimer’s disease

BioMedical Engineering OnLine ◽

10.1186/s12938-021-00931-2 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Xi Mei ◽

Conglong Qiu ◽

Qi Zhou ◽

Zhongming Chen ◽

Yang Chen ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Performance ◽

Retinal Thickness ◽

Vascular Density ◽

Fiber Layer ◽

Mean Values ◽

Registration Number ◽

Clinical Trail ◽

The Difference

Abstract Background Retinal biomarkers of Alzheimer’s disease (AD) have been extensively investigated in recent decades. Retinal nervous and vascular parameters can reflect brain conditions, and they can facilitate early diagnosis of AD. Objective Our study aimed to evaluate the difference in retinal neuro-layer thickness and vascular parameters of patients with AD and healthy controls (HCs). Methods Non-invasive optical coherence tomography angiography (OCTA) was used to determine the combined thickness of the retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL), as well as the full retinal thickness (FRT). The vascular branching (VB), vascular curvature (VC), and vascular density (VD) for AD and HC groups were also obtained. The Mini-Mental State Examination (MMSE) was used to evaluate the cognitive performance of all the participants. After obtaining all the parameters, two-way analysis of variance (ANOVA) was used to compare the mean values of all the retinal parameters of the patients with AD and the HCs. Pearson's correlation was used to test the association between retinal parameters, MMSE scores, and vascular parameters. Results Seventy-eight eyes from 39 participants (19 AD and 20 HC; male, 52.6% in AD and 45.0% in HC; mean [standard deviation] age of 73.79 [7.22] years in AD and 74.35 [6.07] years in HC) were included for the analysis. The average RNFL + GCL thickness (106.32 ± 7.34 μm), FRTs of the four quadrants (290.35 ± 13.05 μm of inferior quadrant, 294.68 ± 9.37 μm of superior quadrant, 302.97 ± 6.52 μm of nasal quadrant, 286.02 ± 13.74 μm of temporal quadrant), and retinal VD (0.0148 ± 0.003) of patients with AD, compared with the HCs, were significantly reduced (p < 0.05). Retinal thickness was significantly correlated with the MMSE scores (p < 0.05). Meanwhile, retinal VD was significantly correlated with the average RNFL + GCL thickness (r2 = 0.2146, p < 0.01). When the vascular parameters were considered, the sensitivity of the AD diagnosis was increased from 0.874 to 0.892. Conclusion Our study suggested that the patients with AD, compared with age-matched HCs, had significantly reduced RNFL + GCL thickness and vascular density. These reductions correlated with the cognitive performance of the participants. By combining nerve and vessel parameters, the diagnosis of AD can be improved using OCTA technology. Trail registration Name of the registry: Chinese Clinical Trail Registry, Trial registration number: ChiCTR2000035243, Date of registration: Aug. 5, 2020. URL of trial registry record: http://www.chictr.org.cn/index.aspx

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Ophthalmic Biomarkers for Alzheimer’s Disease: A Review

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.720167 ◽

2021 ◽

Vol 13 ◽

Author(s):

Ayesha Majeed ◽

Ben Marwick ◽

Haoqing Yu ◽

Hassan Fadavi ◽

Mitra Tavakoli

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Imaging Techniques ◽

Amyloid Β ◽

Neuronal Loss ◽

Fiber Layer ◽

Presenting Symptoms ◽

Non Invasive ◽

The Central Nervous System ◽

Review Current

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by neuronal loss, extracellular amyloid-β (Aβ) plaques, and intracellular neurofibrillary tau tangles. A diagnosis is currently made from the presenting symptoms, and the only definitive diagnosis can be done post-mortem. Over recent years, significant advances have been made in using ocular biomarkers to diagnose various neurodegenerative diseases, including AD. As the eye is an extension of the central nervous system (CNS), reviewing changes in the eye’s biology could lead to developing a series of non-invasive, differential diagnostic tests for AD that could be further applied to other diseases. Significant changes have been identified in the retinal nerve fiber layer (RNFL), cornea, ocular vasculature, and retina. In the present paper, we review current research and assess some ocular biomarkers’ accuracy and reliability that could potentially be used for diagnostic purposes. Additionally, we review the various imaging techniques used in the measurement of these biomarkers.

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Faculty Opinions recommendation of Towards non-invasive diagnostic imaging of early-stage Alzheimer's disease.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725287024.793504193 ◽

2015 ◽

Author(s):

Lawrence Wald

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Diagnostic Imaging ◽

Early Stage ◽

Non Invasive

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Proteins and microRNAs are differentially expressed in tear fluid from patients with Alzheimer’s disease

Scientific Reports ◽

10.1038/s41598-019-51837-y ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 6

Author(s):

Aidan Kenny ◽

Eva M. Jiménez-Mateos ◽

María Ascensión Zea-Sevilla ◽

Alberto Rábano ◽

Pablo Gili-Manzanaro ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Unmet Need ◽

Cost Effective ◽

Specific Protein ◽

Tear Fluid ◽

Initiation Factor ◽

Non Invasive ◽

A Genome ◽

Potential Biomarker

Abstract Alzheimer’s disease (AD) is characterized by a progressive loss of neurons and cognitive functions. Therefore, early diagnosis of AD is critical. The development of practical and non-invasive diagnostic tests for AD remains, however, an unmet need. In the present proof-of-concept study we investigated tear fluid as a novel source of disease-specific protein and microRNA-based biomarkers for AD development using samples from patients with mild cognitive impairment (MCI) and AD. Tear protein content was evaluated via liquid chromatography-mass spectrometry and microRNA content was profiled using a genome-wide high-throughput PCR-based platform. These complementary approaches identified enrichment of specific proteins and microRNAs in tear fluid of AD patients. In particular, we identified elongation initiation factor 4E (eIF4E) as a unique protein present only in AD samples. Total microRNA abundance was found to be higher in tears from AD patients. Among individual microRNAs, microRNA-200b-5p was identified as a potential biomarker for AD with elevated levels present in AD tear fluid samples compared to controls. Our study suggests that tears may be a useful novel source of biomarkers for AD and that the identification and verification of biomarkers within tears may allow for the development of a non-invasive and cost-effective diagnostic test for AD.

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A 36-week multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 clinical trial of sodium oligomannate for mild-to-moderate Alzheimer’s dementia

Alzheimer s Research & Therapy ◽

10.1186/s13195-021-00795-7 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Shifu Xiao ◽

Piu Chan ◽

Tao Wang ◽

Zhen Hong ◽

Shuzhen Wang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Clinical Trial ◽

Controlled Trial ◽

Drug Effects ◽

Disease Assessment ◽

Phase 3 ◽

Double Blind ◽

Double Blind Placebo ◽

The Difference

Abstract Background New therapies are urgently needed for Alzheimer’s disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide with a novel proposed mechanism of action. The first phase 3 clinical trial of GV-971 has been completed in China. Methods We conducted a phase 3, double-blind, placebo-controlled trial in participants with mild-to-moderate AD to assess GV-971 efficacy and safety. Participants were randomized to placebo or GV-971 (900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician’s Interview-Based Impression of Change with caregiver input (CIBIC+), Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). Safety and tolerability were monitored. Results A total of 818 participants were randomized: 408 to GV-971 and 410 to placebo. A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time point, measurable at the week 4 visit and continuing throughout the trial. The difference between the groups in change from baseline was − 2.15 points (95% confidence interval, − 3.07 to − 1.23; p < 0.0001; effect size 0.531) after 36 weeks of treatment. Treatment-emergent adverse event incidence was comparable between active treatment and placebo (73.9%, 75.4%). Two deaths determined to be unrelated to drug effects occurred in the GV-971 group. Conclusions GV-971 demonstrated significant efficacy in improving cognition with sustained improvement across all observation periods of a 36-week trial. GV-971 was safe and well-tolerated. Trial registration ClinicalTrials.gov, NCT02293915. Registered on November 19, 2014

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