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

Abstract

Optical coherence tomography angiography (OCT-A) allows the detection of retinal vessel density (VD) loss, which is a reflection of brain vascular pathology. We aimed to investigate differences in macular VD in the superficial plexus in a large cohort of individuals cognitively unimpaired (CU), with mild cognitive impairment due to Alzheimer´s disease (MCI-AD), MCI due to cerebrovascular pathology (MCI-Va), probable Alzheimer´s disease dementia (ADD) and Vascular Dementia (VaD). Clinical, demographical, ophthalmological and OCT-A data from the Neuro-ophthalmology Research at Fundació ACE (NORFACE) project were analyzed. Differences of macular VD in four quadrants (superior, nasal, inferior and temporal) among the five diagnostic groups were assessed in a multivariate regression model, adjusted by age, sex, education, hypertension, diabetes mellitus, heart disease and stroke. The study cohort comprised 672 participants: 128 CU, 120 MCI-AD, 111 MCI-Va, 257 ADD and 56 VaD. Regression analysis showed a significantly higher VD in the temporal quadrant in MCI-AD compared to CU participants (49.05 ± 4.91 vs 47.27 ± 4.17, p = 0.02, d = 0.40), and a significantly lower VD in the inferior quadrant in MCI-Va compared to CU participants (48.70 ± 6.57 vs 51.27 ± 6.39, p = 0.02, d = 0.40). Individuals with heart disease presented significantly lower VD in the inferior quadrant than those without (p = 0.01). The interaction of sex and diagnosis had no effect in differentiating VD. Mini-Mental State Examination (MMSE) scores were not correlated to VD (all r < 0.16; p > 0.07). In conclusion, our study showed that the MCI-AD and MCI-Va groups had significant differences in macular VD in opposite directions in the temporal and inferior quadrants, respectively, compared to CU participants, suggesting that macular VD might be able to differentiate two pathogenic pathways (AD- and cerebrovascular-related) in early stages of cognitive decline.

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

“…The majority of cohorts reported in the literature, though, were relatively small and the results have not been validated in larger studies. A recent publication from our group, using data from a large clinical cohort, detected higher macular VD in the superficial plexus in MCI due to AD patients compared to cognitively healthy individuals (Marquié et al, 2022), contrary to previous literature results. Importantly, the inclusion of AD biomarkers in OCT-A studies in order to further validate this technique is warranted for the development of the field.…”

“…In particular, we investigated the association of macular VD in the superficial plexus quantified by OCT-A with the AT(N) classification based on cerebrospinal fluid (CSF) Aβ1-42, p181-tau and t-tau measurements. Our hypothesis was that MCI participants with an AD CSF profile (reduced Aβ and elevated tau) would show 10.3389/fnins.2023.1076177 higher macular VD measures than those participants with a normal CSF profile, in line with the results of a recent publication from our group (Marquié et al, 2022).…”

“…In a recent publication by our group, also analyzing macular VD measures from the NORFACE cohort (n = 672), patients clinically defined as MCI-Alzheimer (MCI-AD) and MCI-Vascular (MCI-Va) presented significant differences in macular VD, in opposite directions, in the temporal and inferior quadrants, respectively, compared to cognitively unimpaired (CU) individuals (Marquié et al, 2022). These results suggested that macular VD might be able to differentiate two pathogenic pathways (AD-and cerebrovascular-related) in the early stages of cognitive decline.…”

“…The evaluation comprised: (1) a review of past ophthalmological diseases, treatments and surgeries, (2) monocular visual acuity assessment with the participants wearing their habitual correction for refractive error using a pinhole occluder and the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart (Chew et al, 2009;Bokinni et al, 2015), (3) intraocular pressure (IOP) measurement by Icare tonometry (Pakrou et al, 2008), and (4) swept source (SS) OCT scan. More details can be found elsewhere (Marquié et al, 2022). The ophthalmologist and neurologists were blind to each other's diagnosis.…”

“…The parafoveal area, defined by two concentrical rings measuring 1 and 3 mm in diameter, respectively, was subdivided into four quadrants: nasal, superior, temporal and inferior. More details can be found in a recent publication from the NORFACE cohort (Marquié et al, 2022). The retinal vascular network consists of two separate beds: the superficial vascular plexus, at the level of the ganglion cell layer, and the deep vascular plexus, at the level of the outer plexiform layer (Toussaint et al, 1961).…”