Changes in choroidal thickness quantified by Optical Coherence Tomography across cognitive impairment: data from the NORFACE cohort

Abstract

Background: Optical coherence tomography (OCT) enables high-resolution imaging of ocular structures in health and disease. Choroid thickness (CT) is a key vascular retinal parameter that can be assessed by OCT and might be relevant in the evaluation of the vascular component of cognitive decline. We aimed to investigate CT changes in a large cohort of individuals cognitive unimpaired (CU), with mild cognitive impairment due to Alzheimer's (MCI-AD), mild cognitive impairment due to cerebrovascular disease (MCI-Va), Alzheimer's disease dementia (ADD), and vascular dementia (VaD).

Methods: Clinical, demographical, ophthalmological and OCT data from the Neuro-ophthalmological Research at Fundació ACE (NORFACE) project were analyzed. CT was assessed in the macula across nine Early Treatment Diabetic Retinopathy Study (ETDRS) quadrants, average thickness, total volume, and subfoveal choroidal thickness. Differences of CT among the five diagnostic groups were assessed in a multivariate regression model, adjusting for demographic and cardiovascular risk factors and OCT image quality. A comparison between manual and automatic CT measurements in a subset of participants was also performed.

Results: The study cohort comprised 1,280 participants: 301 CU, 196 MCI-AD, 112 MCI-Va, 578 ADD, and 93 VaD. CT was significantly increased in individuals with cognitive impairment compared to those CU, particularly in the VaD and MCI-Va groups and in the peripheral ETDRS regions. No significant differences were found in inner superior, center and subfoveal choroidal thickness. The interaction of sex and diagnosis had no effect in differentiating CT. Mini-Mental State Examination (MMSE) scores were not correlated to CT. Manual and automated CT measurements showed good reliability.

Discussion: Our findings indicated that peripheral choroidal thickening, especially in patients with cerebrovascular disease, may serve as a potential choroidal biomarker for cognitive decline and suggest different pathogenic pathways in AD and VaD. Further research is required to explore CT as a reliable ocular biomarker for cognitive impairment.

Keywords: Alzheimer's disease; Biomarkers; Choroidal thickness; NORFACE cohort; Optical coherence tomography; Vascular dementia.

Fig. 1

OCT imaging protocol. a Limits of automated CT measurements focused on SFCT, which refers to the thickness of the choroid directly beneath the fovea. The measurement of SFCT is obtained from Bruch's membrane (upper boundary) to the choroid-scleral interface (CSI) (lower boundary). b The 3 measurement radii are shown: a 1 mm radius corresponding to the central region, a 3 mm radius corresponding to the inner measurements, and a 6 mm radius corresponding to the outer measurements. c The ETDRS grid in the macular region of the right eye represents the 9 ETDRS quadrants with the respective CT measurements. The scan range is 6 × 6 mm. d along with the assigned names and their respective ETDRS quadrants. Abbreviations: CT = choroidal thickness; CSI = choroid-scleral interface; ETDRS = Early Treatment Diabetic Retinopathy Study quadrants; OCT = optical coherence tomography; SFCT = subfoveal choroidal thickness

Fig. 2

Protocol for comparison of manual and automated CT measurements. a SFCT, which represents the thickness of the choroid directly beneath the fovea, was the first measurement performed. b Four additional CT measurement points were performed: two at 500 µm (Superior and Inferior) and two at 1500 µm (Superior and Inferior). These are measured manually using the “caliper tool,” visible at the top of the image. c Activation of the automated measurement software on the Triton DRI-OCT, using the CSI protocol, which measures CT from Bruch's membrane (upper boundary) to the choroid-scleral interface (CSI) (lower boundary) highlighting its defined boundaries. d Use of the “caliper tool” to perform automated measurements, facilitating comparison between manual and automated methods, detailed at the bottom of the image. Abbreviations: CT = choroidal thickness; CSI = choroid-scleral interface; DRI-OCT = Deep Range Image Optical Coherence Tomography; SFCT = subfoveal choroidal thickness

Fig. 3

Selection algorithm flowchart. Abbreviations: ADD = Alzheimer´s disease dementia; AMD = age-related macular degeneration; CT = choroidal thickness; CU = cognitively unimpaired; CV = cerebrovascular; IOP = intraocular pressure; MCI-AD = mild cognitive impairment due to Alzheimer´s disease; MCI-Va = mild cognitive impairment due to CV pathology; MMSE = Mini Mental State Examination; VaD = vascular dementia

Fig. 4

Differences in CT between diagnostic groups. The Y-axis represents adjusted CT (µm), while the X-axis denotes diagnostic groups. The names of each ETDRS region are displayed at the top of each panel: a Central; b Inner Temporal; c Inner Superior; d Inner Nasal; e Inner Inferior; f Outer Temporal; g Outer Superior; h Outer Nasal; i Outer Inferior; j Average thickness; k Subfoveal choroidal thickness; l Total volume. (*) Significance was corrected with Bonferroni for multiple comparisons (p < 0.004). Abbreviations: ADD = Alzheimer´s disease dementia; CT = choroidal thickness; CU = cognitively unimpaired; CV = cerebrovascular; MCI-AD = mild cognitive impairment due to Alzheimer´s disease; MCI-Va = mild cognitive impairment due to CV pathology; VaD = vascular dementia