Novel noninvasive biomarkers of prodromal Alzheimer disease: The role of optical coherence tomography and optical coherence tomography–angiography

Abstract

Background and purpose A reduction of retinal thickness and an alteration of retinal perfusion have been found in Alzheimer disease (AD). Nowadays, retinal layers and retinal perfusion can be evaluated by means of noninvasive imaging techniques, namely, optical coherence tomography (OCT) and OCT‐angiography (OCT‐A). Here, we have compared the retinal thickness and the perfusion index, measured by means of OCT and OCT‐A, in patients with mild cognitive impairment due to AD (MCI‐AD) and in age‐ and sex‐matched cognitively healthy controls. Methods Twenty‐four MCI‐AD patients and 13 control subjects were enrolled. MCI‐AD patients underwent lumbar puncture; all of them showed a cerebrospinal fluid (CSF) profile compatible with AD. OCT was used for evaluating retinal volumes and thicknesses, whereas with OCT‐A we measured fractal dimension (FD), vascular perfusion density (VPD), and vessel length density (VLD) of superficial capillary plexus (SCP), intermediate capillary plexus (ICP), deep capillary plexus (DCP), and choriocapillaris. The comparisons between groups were made after adjustment for age, diabetes, and hypertension. Results A significant reduction of SCP‐VLD (p = 0.012), ICP‐VPD (p = 0.015), ICP‐VLD (p = 0.004), DCP‐VPD (p = 0.012), and DCP‐VLD (p = 0.009) was found in MCI‐AD patients compared to controls. Conversely, FD was higher in MCI‐AD than in controls (p = 0.044). CSF Aβ42/total tau negatively correlated with FD (r = −0.51, p = 0.010). Conclusions OCT‐A might have a potential role in detecting new noninvasive biomarkers for early AD detection. Retinal VPD might identify amyloid angiopathy‐related chronic injury, and FD could show early vessel recruitment as a compensative mechanism at disease onset. Further studies will be needed to confirm these findings.

Differences in macular vessel density in the superficial plexus across cognitive impairment: the NORFACE cohort

“…First, van de Kreeke et al reported a significantly higher VD in both peripapillary and macular regions in 13 Aβ + compared to 111 Aβ- cognitively healthy twins, but no differences in the FAZ size 23 . Biscetti et al showed higher measures of fractal dimension in a group of 24 MCI with a CSF AD-profile compared to a group of 13 controls 24 .…”

“…Jiang et al showed similar results in a cohort of 12 ADD patients, 19 MCI patients and 21 controls 17 . Biscetti et al showed a significant reduction in both vascular perfusion density and vessel length density in a group of 24 MCI with a CSF AD-profile compared to a group of 13 controls 24 . Querques et al used dynamic vessel analyzer in a cohort of ADD, MCI and controls, and showed that the retinal neurovascular coupling was significantly impaired in ADD and MCI compared to controls 18 .…”

Cognitive Dysfunctions in Glaucoma: An Overview of Morpho-Functional Mechanisms and the Impact on Higher-Order Visual Function

“…The link between these two apparently different conditions is further reinforced by the common finding of RNFL/GCL thinning and visual gray and white matters morpho-functional impairments (Iseri et al, 2006;Tamura et al, 2006;Ascaso et al, 2014;Jones-Odeh and Hammond, 2015). The relationship between retinal and CNS alterations is strong and support the role of OCT-based technology for the early diagnosis of cognitive dysfunctions and neurodegenerative diseases (Biscetti et al, 2021). A well-known glaucoma-related finding is the thinning of the lamina cribrosa, a complex tissue surrounding the ONH and providing structural and functional supports to the ganglion cells.…”

Macular vessel density in the superficial plexus is not associated to cerebrospinal fluid core biomarkers for Alzheimer’s disease in individuals with mild cognitive impairment: The NORFACE cohort

“…In particular, the retina is considered a "window into the brain" and can be accessed noninvasively through optical coherence tomography (OCT), which is a fast, inexpensive, non-invasive and widely accessible tool used for the diagnosis and monitoring of common ocular pathologies (Jaffe and Caprioli, 2004). The study of retinal biomarkers for AD started with the analysis of structural parameters (e.g., thickness and volume of the different retinal layers in the peripapillary and macular regions) and more recently, investigators have focused on the study of the retinal microvasculature [e.g., vessel density (VD) and size of the foveal avascular zone, mainly] (Jiang et al, 2018;Querques et al, 2019;Wu et al, 2020;Biscetti et al, 2021). Besides, the retinal microvascular network can be directly assessed in vivo using high-resolution OCT-angiography (OCT-A), while this cannot be done for cerebrovascular disease with brain imaging techniques.…”

“…Thus, OCT-A measures in the retina could be used as a proxy of brain vascular changes. Several publications have demonstrated abnormalities in retinal vascular parameters in AD and MCI patients compared to healthy controls, such as increases in the foveal avascular zone (FAZ) and decreases in VD (Cheung et al, 2014;Grewal et al, 2018;Jiang et al, 2018;Querques et al, 2019;Zabel et al, 2019;Zhang et al, 2019;Wu et al, 2020;Biscetti et al, 2021;Chalkias et al, 2021;Rifai et al, 2021), pointing to retinal vascular loss. The majority of cohorts reported in the literature, though, were relatively small and the results have not been validated in larger studies.…”