Retinal Nerve Fiber Layer Thinning in Alzheimer's Disease: A Case-Control Study in Comparison to Normal Aging, Parkinson's Disease, and Non-Alzheimer's Dementia (original) (raw)
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Clinical Ophthalmology
Objective: To evaluate the feasibility of using optical coherence tomography (OCT) for the detection of Alzheimer's disease (AD), by measuring the thickness of the retinal nerve fiber layer (RNFL) and the ganglion cell layer and inner plexiform layer (GCL-IPL). Material and Methods: This was a single-center, cross-sectional study. The study included 29 patients with AD (mean age ± standard deviation: 75.61 ± 6.24 years) and 29 healthy age-and sex-matched controls. All participants underwent cognitive evaluations using the Montreal Cognitive Assessment test. Measurements of the RNFL thickness, as well as GCL-IPL thickness, were obtained for all participants using OCT. Both RNFL and GCL-IPL parameters were adjusted for best-corrected visual acuity, hypertension, diabetes and dyslipidemia. Results: The mean RNFL thickness was significantly thinner in the AD group than in the control group (85.24 and 90.68 µm, respectively, adjusted P=0.014). The superior quadrant was thinner in the AD group (adjusted P=0.033). The thicknesses did not differ significantly between groups for the other quadrants. The mean GCL-IPL thickness in the AD (68.81 µm) was significantly thinner than that in the controls (76.42 µm) (adjusted P=0.014). Overall, there was a negative correlation between age and mean RNFL; and between age and GCL-IPL thickness (r=−0.338, P=0.010 and r=−0.346, P=0.008, respectively). Conclusion: The mean RNFL and GCL-IPL thicknesses were thinner in the AD group than in the control group. These findings suggest that RNFL and GCL-IPL thickness may be biological markers for AD.
Scientific reports, 2018
The use of optical coherence tomography (OCT) has been suggested as a potential biomarker for Alzheimer's Disease based on previously reported thinning of the retinal nerve fiber layer (RNFL) in Alzheimer's disease's (AD) and Mild Cognitive Impairment (MCI). However, other studies have not shown such results. 930 individuals (414 cognitively healthy individuals, 192 probable amnestic MCI and 324 probable AD) attending a memory clinic were consecutively included and underwent spectral domain OCT (Maestro, Topcon) examinations to assess differences in peripapillary RNFL thickness, using a design of high ecological validity. Adjustment by age, education, sex and OCT image quality was performed. We found a non-significant decrease in mean RNFL thickness as follows: control group: 100,20 ± 14,60 µm, MCI group: 98,54 ± 14,43 µm and AD group: 96,61 ± 15,27 µm. The multivariate adjusted analysis revealed no significant differences in mean overall (p = 0.352), temporal (p = 0,119...
Acta Ophthalmologica, 2012
the retina is an attractive source of biomarkers since it shares many features with the brain. thickness differences in 10 retinal layers between 19 patients with mild Alzheimer's disease (AD) and a control group of 24 volunteers were investigated. Retinal layers were automatically segmented and their thickness at each scanned point was measured, corrected for tilt and spatially normalized. When the mean thickness of entire layers was compared between patients and controls, only the outer segment layer of patients showed statistically significant thinning. However, when the layers were compared point-by point, patients showed statistically significant thinning in irregular regions of total retina and nerve fiber, ganglion cell, inner plexiform, inner nuclear and outer segment layers. Our method, based on random field theory, provides a precise delimitation of regions where total retina and each of its layers show a statistically significant thinning in AD patients. All layers, except inner nuclear and outer segments, showed thickened regions. new analytic methods have shown that thinned regions are interspersed with thickened ones in all layers, except inner nuclear and outer segments. Across different layers we found a statistically significant trend of the thinned regions to overlap and of the thickened ones to avoid overlapping. Alzheimer's disease (AD) is an increasing health issue for elderly people and healthcare services in developed countries. There is wide agreement about the relevance of its early detection, leading to interest in early, convenient and affordable biomarkers. The brain is the main tissue affected in AD, and the retina is the only neuronal tissue that can be analyzed non-invasively in AD. Increasing evidence suggests that retinal analysis can provide insights into brain pathology. In a sample of 2,124 patients with mild AD, Mutlu et al. found that a thinner ganglion cell layer (GCL), nerve fiber layer (NFL) and inner plexiform layer (IPL) are associated with smaller grey matter, white matter and hippocampal volume 1. Ong et al. found that thinner total retinal thickness is associated with smaller grey matter volume only in the temporal lobe, whereas thinner GC-IPL complex is associated with smaller grey matter and white matter volumes in the temporal lobe, as well as smaller grey matter volume in the occipital lobe 2. Casaletto et al. found thinner retinal thickness and GCL to be related to medial temporal lobe atrophy 3. In a homogeneous sample of patients with early-stage AD, Salobrar-Garcia et al. 4 found that peripapillary total retinal thinning accompanies AD development. More recently, our group has found that retinal thinning in the macular area appears at a very early stage of AD 5 , together with a 40% decrease in contrast sensitivity 6. All these findings converge to demonstrate that the volume of brain structures involved in AD is related to retinal thickness and visual function. This suggests that AD-associated neuronal damage and deposits may occur in the retina before they occur in the brain, implying that retinal analyses could allow AD detection during the asymptomatic preclinical period 7,8. Ten retinal layers were segmented and studied: nerve fiber layer (NFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), inner
The Retinal Nerve Fiber Layer Thickness in Patients with Alzheimer’s Dissease
Saudi Journal of Medicine
Aim: To investigate the retinal nerve fiber layer (RNFL) thickness in patients with Alzheimer disease (AD) without visual impairment using optical coherence tomography (OCT) and to compare the results with healthy control. Study Design: Case Control, Quantities, non-randomized study. Methods and materials: This study was conducted in the neurology and ophthalmology department, King Faisal Specialized hospital, Riyadh, Saudi Arabia from January 2015 to April 2015. Sample: This study was included 22 participants, 11 Alzheimer's patients and 11 healthy controls between the age of 50-75 years old female and male. Examinations: After sinning the informed consent, a number of examinations in the ophthalmology performed and the retinal nerve fiber layer thickness was measured by 3D OCT-2000 Spectral Domain OCT. Statistical Analysis: All statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS), version 21.0, for MacBook Pro. Data were expressed as mean ± standard deviation. All the data were analyzed and compared using Mann-Whitney U test. A P-value ≤ 0.05 was considered to indicate statistical significance. Results: Patients with AD showed a significant reduction in the total RNFLT compared to the control group (84.21 ± 12.68 μm versus 98.27 ± 16.25 μm; P = 0.006). Furthermore, the nasal and inferior RNFL thickness were significantly lower in patients with AD compared to the controls with a P = 0.007 and P = 0.010 in the nasal and the inferior quadrant, respectively. Also, no significant thinning in the temporal and the superior quadrant in AD retinal nerve fiber layer was detected. Conclusion: Patients with Alzheimer disease exhibit a thinner retinal nerve fiber layer (RNFL) than the healthy control subjects.
Journal of Neurology, 2014
Retinal nerve fiber layer thickness (RNFL) measured by means of Optical Coherence Tomography (OCT) has been used as a marker not only of ophthalmologic diseases but also of neurodegenerative diseases such as Alzheimer's disease (AD) and mild cognitive impairment (MCI). The purpose of this work was to demonstrate that patients with amnestic MCI show an intermediate RNFL thickness between normality and AD, and a macular volume and thickness as well. In a cross-sectional study we consecutively recruited 18 patients with AD, 21 with MCI, and 41 healthy controls. OCT was performed in all of them to measure circumpapillary RNFL thickness in lm, as well as macular volume and thickness. In the analysis of variance we saw that RNFL was thinner in MCI patients compared with controls, and it was also thinner in AD patients compared with MCI patients and controls. With regard to the macular measurements in mm 3 , MCI patients had the greatest macular volume in comparison with AD patients and controls. In turn the controls had greater macular volume than AD patients. The decreased RNFL thickness in MCI and AD patients suggests loss of retinal neurons and their axons. The increased thickness and macular volume have never been reported before in aMCI. This finding could be explained by inflammation and/or gliosis in early stages of AD. OCT could be a useful marker of AD for early detection and monitoring progression.
Abnormal retinal thickness in patients with mild cognitive impairment and Alzheimer's disease
Neuroscience Letters, 2007
In Alzheimer's disease (AD), brain lesions are marked by severe neuronal loss and retinal degeneration was previously mentioned in affected patients. Mild cognitive impairment (MCI) is a clinical syndrome that could be an early phase of AD. In this study, using optical coherence tomography (OCT), the retinal nerve fiber layer (RNFL) thickness was assessed in patients with mild AD, moderate to severe AD, amnestic MCI and control subjects. The results show that RNFL thickness is statistically reduced in patients with MCI, mild AD or moderate to severe AD compared to controls. In addition, no statistical difference was found between the results in MCI patients and mild AD patients. The RNFL seems to be involved early during the course of amnestic MCI and OCT tests could be carried out in patients with cognitive troubles.
Basic and Clinical Neuroscience (BCN), 2022
Alzheimer disease (AD) is the most common form of dementia worldwide. The modalities to diagnose AD are generally expensive and limited. Both the central nervous system (CNS) and the retina are derived from the cranial neural crest; therefore, changes in retinal layers may reflect changes in the CNS tissue. Optical coherence tomography (OCT) machine can show delicate retinal layers and is widely used for retinal disorders. This study aims to find a new biomarker to help clinicians diagnose AD via retinal OCT examination. Methods: After considering the inclusion and exclusion criteria, 25 patients with mild and moderate AD and 25 healthy subjects were enrolled in the study. OCT was done for all eyes. The central macular thickness (CMT) and the ganglion cell complex (GCC) thickness were calculated. The groups were compared using the SPSS software, v. 22. Results: Both GCC thickness and CMT were significantly decreased in patients with AD when compared to healthy age-and sex-matched individuals. Conclusion: Retinal changes, specifically CMT and GCC thickness, may reflect the AD process in the brain. OCT can be considered a non-invasive and inexpensive method to help diagnose AD.
PloS one, 2018
Inner retina in Alzheimer's Disease (AD) may experience neuroinflammation resulting in atrophy. The objective of our study was to determine whether retinal GCIPL (ganglion cell-inner plexiform layer) or nerve fiber layer (NFL) thickness may serve as noninvasive biomarkers to diagnose AD. This cross-sectional case-control study enrolled 15 mild cognitive impairment (MCI) patients, 15 mild-moderate AD patients, and 18 cognitively normal adults. NFL and GCIPL thicknesses on optical coherence tomography (OCT) were measured using Duke Optical Coherence Tomography Retinal Analysis Program (DOCTRAP) and Spectralis software. We demonstrated that regional thicknesses of NFL or GCIPL on macular or nerve OCTs did not differ between groups. However, a multi-variate regression analysis identified macular areas with a significant thickening or thinning in NFL and GCIPL in MCI and AD patients. Our primary findings controvert previous reports of thinner NFL in moderate-to-severe AD. The areas o...