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

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

The correlation of retinal neurodegeneration and brain degeneration in patients with Alzheimer’s disease using optical coherence tomography angiography and MRI

“…The MMSE assesses the overall cognitive function and has a higher sensitivity in identifying patients with dementia ( Carpinelli Mazzi et al, 2020 ). Some studies demonstrated that retinal thickness was associated with MMSE score in AD patients ( Kim and Kang, 2019 ; Mei et al, 2021 ), while other researchers didn’t find such associations which are consistent with our results ( Cipollini et al, 2020 ; Zhao et al, 2020 ). However, Li et al (2018) reported that the Mini-Cog was superior to MMSE in identifying Chinese outpatients with mild cognitive impairment, which was less affected by age and education level than MMSE.…”

Optical coherence tomography and angiography in Alzheimer's disease and other cognitive disorders

“…Recent OCT studies have indicated that macular GCL + was reduced in AD patients compared with age-matched controls, 10,40,42,48,51 further implicating retinal neurodegeneration mechanism in AD.…”

“…Most studies did not find a significant difference between MMSE score and OCT parameters. 65,71 However, some studies reported a significant correlation between MMSE score and RNFL; 40,51,62,72,75 GCL 40,51,52,74,76 and CT. 53 Therefore, the correlation between the clinical severity of AD and the thickness of the retinal layers is not well established. In our study, after adjustment of the MMSE score with the duration of disease progression, we found a significant correlation with GCL + + and GCL + , in AD group.…”

“…Measurement of RNFL thickness using OCT has attracted considerable interest with several studies reporting a significant decrease in overall mean RNFL thickness in AD patients compared with controls. 10,35,40 RNFL thickness appeared to have potential utility in the diagnosis of AD. 35,41 Indeed, we noted a significant difference in mRNFL thickness between AD patients and other types of dementia group in our study.…”

Development of a Novel Retina−Based Diagnostic Score for Early Detection of Major Depressive Disorder: An Interdisciplinary View

“…The retina is the only visualized neurovascular tissue in the body, providing an easy-to-see window for monitoring systemic neurovascular conditions ( 30 , 31 ). OCTA is a novel, non-invasive and quantitative retinal imaging tool of which use has been extended from early screening and monitoring of fundus diseases to systemic diseases ( 32 – 35 ). OCTA-base retinal parameters, such as retinal vessel density and thickness, are expected to be one of the most promising and competitive non-invasive indicators in clinical practice.…”