Changes In Retinal Thickness And Microvasculature In Association With Cognitive Function And Apolipoprotein E4 Genotype In Alzheimer’s Disease And Mild Cognitive Impairment

Objective: The purpose of this study was to analyze the existence of possible changes in retinal thickness and vascular density in patients with Alzheimer’s disease(AD)and mild cognitive impairment(MCI)by optical coherence tomography(OCT)and optical coherence tomography angiography(OCTA),to investigate the correlation between those changes and cognitive functions,and to evaluate the diagnostic value of OCT and OCTA techniques for MCI and AD.Another aim of the present study was to analyze the effect on the retina of different ApoEε4 allele carriage status.We ventured to explore potential retinal biomarkers for both MCI and AD.Methods: Participants with MCI and AD,as well as cognitively normal healthy controls(HC)who were age,gender and education level matched were included in this cross-sectional study.Cognitive function evaluations were performed using the Mini-Mental State Examination(MMSE)and the Montreal Cognitive Assessment(Mo CA).Retinal thickness and vascular density were obtained by OCT and OCTA.For each participant,the right eye was first selected for analysis,and the left eye was used as a substitute if the image quality of the right eye was poor or with a combined retinal pathology.Statistical analysis was performed using SPSS26.0,a p value <0.05 was considered significant.One-way ANOVA was used to investigate the difference between MCI,AD and HC groups,Pearson correlation analysis was used to investigate the correlation between retinal thickness,vascular density and cognitive function.Independent Sample Student’s T-Test and Mann-Whitney U-Test were used to analyze whether there were differences in retinal structure and microvasculature between patients with different ApoEε4 carriage status.Results: 78 MCI,74 AD and 80 HC participants were recruited in our study.Characteristics like gender,age,visual acuity,intraocular pressure and education level were not statically different between the three groups.All participants underwent an OCT examination.40 MCI,47 AD and 40 HC participants underwent an OCTA examination.The ApoE genotype was evaluated in 50 participants including 21 MCI and 29 AD participants.1.Comparison of OCT parameters between MCI,AD and HC groupsMacular thickness and volume: Significant decreases in the GC-IPL(p<0.001),the average macular thickness(p<0.001),all sectors of the macular inner and outer ring thickness(p<0.05),and the MV(p<0.001)were observed in the MCI and AD groups compared to the HC group,no statistically significant difference was found in the central macular thickness.Retinal nerve fiber layer(RNFL): Significant decreases in the average(p<0.001),inferior sector(p<0.05),superior sector(p<0.05)and temporal sector(p<0.001)of RNFL were observed in the MCI and AD groups compared to the HC group.No statistically significant difference was found in the nasal sector of RNFL.2.Comparison of OCTA parameters between MCI,AD and HC groupsSuperficial capillary plexus(SCP): Significant decreases in the whole image area,parafovea area and perifovea area of SCP vascular density were observed in the MCI and AD groups compared to the HC group(p<0.05).No statistical significant difference of vascular density was found in the fovea area(p>0.05).Deep capillary plexus(DCP): Significant decreases in the fovea area of DCP vascular density were observed in the AD group compared to the HC and MCI groups(p<0.05).In the inferior sector of parafovea area,vascular density was significantly decreased in the AD group compared to the HC group(p<0.05),with no statistical difference between the three groups in the remaining areas(p>0.05).Parameters of the foveal avascular zone: Significant increased A-circularity index(AI)and decreased vascular density in the 300 μm area adjacent to the fovea(FD-300)in the MCI and AD groups were observed compared to the HC group(p<0.001).No statistical differences were observed between the three groups in the area and perimeter of the foveal avascular zone(p>0.05).Optic disc microvasculature: Significant decreases in the whole image vascular density,the inside disc vascular density,the peripapillary radial capillaries(RPC)vascular density in the average,IN sector,IT sector,TI sector,TS sector and ST sector were observed in the MCI and AD groups compared to the HC group(p < 0.05).3.The correlation between retinal thickness,vascular density and cognitive functionCorrelation between retinal thickness,vascular density and MMSE scores:FD-300,the whole image vascular density of optic disc,the RPC vascular density in the average,IT sector,TI sector,TS sector and ST sector had a significant positive correlation with the MMSE scores(p < 0.05).Correlations between retinal thickness,vascular density and Mo CA scores:average and temporal RNFL thickness,average and inner nasal macular thickness,the SCP parafovea vascular density in the average,tempo sector and superior,FD-300,the optical vascular density in the whole image and inside disc,the RPC vascular density in the TI sector,TS sector and ST sector had a significant positive correlation with the Mo CA scores(p < 0.05).AI had a negative correlation with the Mo CA scores(p < 0.05).4.Diagnostic ability of OCT,OCTA parameters in MCI and ADThe diagnostic efficacy of OCT and OCTA parameters for MCI and AD was evaluated by the area under the relative ROC curve(AUC).Average RNFL thickness,GC-IPL thickness,macular volume,average macular thickness,whole image,inside disc and RPC vascular density of the optic disc,whole image,parafovea and perifovea vascular density of the SCP,FD-300 and AI all have some value in the diagnosis of MCI and AD.FD-300 had the largest area under the curve in both MCI and AD(AUC:MCI=0.753,AD=0.797).5.Comparison of OCT and OCTA parameters between APOE-ε4 carriers and non-carriers in MCI and ADCompared to participants who did not carry ApoEε4,statistically significant decreases of the GC-IPL thickness,FD-300,the SCP parafovea vascular density in the superior and nasal sectors were observed in the ApoEε4 carriers(p<0.05).Conclusion:1.MCI and AD patients had decreased retinal thickness and vascular density compared to healthy controls.Retinal thickness and vascular density were positively correlated with cognitive function.Retinal neurodegenerative and microvascular changes may reflect the decline in cognitive function of the MCI and AD patient.2.Non-invasive OCT and OCTA techniques may contribute to the early identification of MCI and AD.Retinal thickness and vascular density have potential utility as diagnostic biomarkers of MCI and AD.3.Carrying ApoEε4 may aggravate retinal neurodegeneration and microvascular dysfunction in patients with MCI and AD.