Choriocapillaris and Retinal Vascular Alterations in Presymptomatic Alzheimer's Disease

Abstract

Purpose To compare optical coherence tomography angiography (OCTA) retina metrics between cognitively healthy subjects with pathological versus normal cerebrospinal fluid (CSF) Aβ 42 /tau ratios. Methods Swept-source OCTA scans were collected using the Zeiss PLEX Elite 9000 and analyzed on 23 cognitively healthy (CH) subjects who had previously undergone CSF analysis. Thirteen subjects had a pathological Aβ 42 /tau (PAT) ratio of <2.7132, indicative of presymptomatic Alzheimer's disease (AD), and 10 had a normal Aβ 42 /tau (NAT) ratio of ≥2.7132. OCTA en face images of the superficial vascular complex (SVC) and deep vascular complex were binarized and skeletonized to quantify the perfusion density (PD), vessel length density (VLD), and fractal dimension (FrD). The foveal avascular zone (FAZ) area was calculated using the SVC slab. Choriocapillaris flow deficits (CCFDs) were computed from the en face OCTA slab of the CC. The above parameters were compared between CH-PATs and CH-NATs. Results Compared to CH-NATs, CH-PATs showed significantly decreased PD, VLD, and FrD in the SVC, with a significantly increased FAZ area and CCFDs. Conclusions Swept-source OCTA analysis of the SVC and CC suggests a significant vascular loss at the CH stage of pre-AD that might be an indicator of a neurodegenerative process initiated by the impaired clearance of Aβ 42 in the blood vessel wall and by phosphorylated tau accumulation in the perivascular spaces, a process that most likely mirrors that in the brain. If confirmed in larger longitudinal studies, OCTA retinal and inner choroidal metrics may be important biomarkers for assessing presymptomatic AD.

Choriocapillaris reduction accurately discriminates against early‐onset Alzheimer's disease

“…Moreover, a wide range of retinal microvascular and choriocapillaris changes in AD patients such as lower densities, sparser vasculature, increased tortuosity, and lower fractal dimensions have been shown in OCTA studies. 8 , 49 , 50 , 51 , 52 , 53 Here we showed that EOAD patients had lower retinal microvascular and choriocapillaris densities and sparser retinal microvascular and choriocapillaris compared to controls. These findings are in line with previous OCTA analyses.…”

Association between retinopathy and risk of dementia in a general Japanese population: the Hisayama Study

“…The exact mechanisms underlying this association remain unclear, but the cerebral neurodegenerative changes leading to AD may result in similar pathological changes in the retinal microvasculature. Decreased retinal circulation has been reported in studies of patients with AD 41 . Neurotoxicity due to the accumulation of amyloid-β in the retinal vasculature may also cause damage to vascular epithelial cells, leading to retinal microvascular damage 42 .…”