Study Of The Correlation Of Fundus Changes And Cognition In Cerebral Small Vessel Disease And Neural Mechanisms

BackgroundCerebral small vessel disease(CSVD)is a syndrome of clinical,cognitive,neuroimaging and neuropathological changes resulting from lesions of the small vessels(small penetrating arteries and arterioles,capillaries and small veins)in the brain from a variety of etiologies.CSVD is the most important vascular contributor to dementia,causing not only vascular mild cognitive impairment that does not reach the severity of dementia,but can also account for 36% to 67% of vascular dementia.Currently commonly used neuroimaging,such as computed tomographic angiography or magnetic resonance angiography,may not detect many of the brain mechanisms underlying subclinical changes due to limitations in spatial resolution(<100-500μm resolution).Therefore,there is an urgent need for alternative clinical markers to quantify the subtle degeneration and microvascular changes associated with CSVD.Optical coherence tomography angiography(OCTA)is a novel and noninvasive technique for the quantitative assessment of retinal microvascular and institutional changes.Since the retinal and cerebral small vessels share similar embryological origins,anatomical features,and physiological properties,altered fundus of the eye might provide a new perspective on the mechanisms of CSVD.ObjectiveWe aimed to investigate whether there are differences in retinal thickness and vascular density between CSVD patients and healthy older adults using OCTA,and the relationship between fundus changes and cognitive function in CSVD patients,and to further explore the neural mechanisms involved.Methods40 CSVD patients and 33 healthy controls(HC)were recruited to participate in the study.All subjects underwent a detailed ophthalmic and neurological examination.Using OCTA to assess retinal microvascular perfusion in all subjects,the vessel density of the superficial capillary plexus(SCP),deep capillary plexus,and radial peripapillary capillary(RPC)in the retina was quantified,as well as the area of the foveal avascular zone.The thickness of the macular internal limiting membrane-inner plexiform layer and peripapillary retinal nerve fiber layer(RNFL)were also quantified.All subjects completed a standard set of neuropsychological tests to assess overall cognitive functioning and individual domain cognitive functioning,including Hamilton depression scale,Hamilton anxiety scale,Montreal cognitive assessment(Mo CA),auditory verbal learning test(AVLT),Stroop’s color word test(SCWT),color trail test(CTT),verbal fluency test and digital span(DS).All subjects underwent cerebral magnetic resonance imaging(MRI)scans,and the number of lacunar infarcts and the severity of periventricular and deep white matter hyperintensities(PWMHs/DWMHs)were assessed on the basis of MRI images.The grey matter volume and structural brain network topology properties of CSVD patients were analyzed using structural images and diffusion tensor images,respectively.ResultsRetinal vessel density was significantly lower in the CSVD patients than in the HC group,specifically in the temporal(P = 0.008),nasal(P = 0.023)and inferior quadrants(P = 0.032)of the retinal SCP and the nasal superior(P = 0.035)and superior nasal quadrants(P = 0.014)of the peripapillary RPC network.In addition,peripapillary RNFL thickness was significantly lower in the temporal inferior quadrant in CSVD patients compared to the HC group(P = 0.017).For cognitive function,CSVD patients had significantly lower overall cognitive function(Mo CA;P = 0.002),memory function(AVLT-immediate,AVLT-delayed,AVLT-recognition;P < 0.05),information processing speed(CTT-A,SCWT-word;P < 0.05)and executive function(CTT-B;P = 0.042)compared to the HC group.Multi-factor linear regression analysis showed that after correction for hypertension,diabetes and hyperlipidemia,vessel density in the temporal,nasal and inferior quadrants of retinal SCP in CSVD patients was significantly and negatively correlated with PWMHs(temporal: B =-1.577,95%CI =-3.059;-0.095,nasal:B =-2.089,95%CI =-3.645;-0.533,inferior: B =-2.580,95%CI =-4.802;-0.358)and DWMHs(temporal: B =-1.529,95%CI =-2.838;-0.220,nasal: B =-1.756,95%CI =-3.144;-0.367,inferior: B =-2.576,95%CI =-4.530;-0.622).In addition,vessel density in the temporal,nasal and inferior quadrants of retinal SCP in CSVD patients was significantly correlated with cognitive function(P < 0.05),particularly overall cognitive function(Mo CA),memory function(AVLT-immediate),information processing speed(SCWT-word),executive function(SCWT-color word,CTT-B)and attentional function(DS-forward/backward).Also,vessel density in the temporal quadrant of the retinal SCP in CSVD patients had a significant negative correlation with shortest path length(r =-0.265,P = 0.018)and significant positive correlations with global efficiency(r = 0.026,P = 0.144),rich club connections(r = 0.246,P = 0.029)and feeder connections(r = 0.255,P = 0.024).Vessel density in the nasal quadrant had a significant negative correlation with shortest path length(r =-0.242,P = 0.033).ConclusionCSVD patients have decreased retinal perfusion and thinning of RNFL thickness,and retinal hypoperfusion was significantly related to cognitive function and structural brain network,suggesting that these parameters could have potential utility as biomarkers of CSVD.