Abstract

Evidence is accumulating that cognitive function, and visual impairment may be related. In this pilot study, we investigated whether multifractal dimension and lacunarity analyses performed in sectoral regions of the retina may reveal changes in patients with cognitive impairment (CI) that may be masked in the study considering the whole retinal branching pattern. Prospective age-matched subjects (n = 69) with and with no CI and without the presence of any ophthalmic history were recruited (age > 55+ years). The Montreal Cognitive Assessment (MoCA) was used to measure CI, and full-field electroretinogram (ERG) was performed. Also, visual performance exams were conducted using the Rabin cone contrast test (CCT). Quantification of the retinal structure was performed in retinal fundus images [45o field of view (FOV), optic disk centered] with excellent quality for all individuals [19 healthy controls (HC) and 20 patients with CI] after evaluating the inclusion and exclusion criteria in all study participants recruited (n = 69). The skeletonized vasculature network that comprised the whole branching pattern observable in the full 45° FOV was obtained for each image and divided into nine equal regions (superotemporal, superior, superonasal, macular, optic disk, nasal, inferotemporal, inferior, and inferonasal). The multifractal behavior was analyzed by calculating the generalized dimension Dq (Do, D1, and D2), the lacunarity parameter (Λ), and singularity spectrum f(α) in the nine sectoral skeletonized images as well as in the skeletons that comprised the whole branching pattern observable in the full 45° FOV. The analyses were performed using the ImageJ program together with the FracLac plug-in. Independent sample t-tests or Mann Whitney U test and Pearson correlation coefficient were used to find associations between all parameters in both groups. The effect size (Cohen’s d) of the difference between both groups was also assessed. A p-value < 0.05 was considered statistically significant. Significant correlations between multifractal and Λ parameters with the MoCA and implicit time ERG-parameter were observed in the regional analysis. In contrast, no trend was found when considering the whole retinal branching pattern. Analysis of combined structural-functional parameters in sectoral regions of the retina, instead of individual retinal biomarkers, may provide a useful clinical marker of CI.

Highlights

  • The impending growth in the number of people living with dementia will place significantly higher demands on both national and international healthcare (Hampel et al, 2018)

  • Potential subjects with cognitive impairment (CI) were identified from the clinic or recruited from a population attending adult care centers and community clinics using available medical records [e.g., Clinical Dementia Rating scale (CDR), mini-mental state examination (MMSE), and neuropsychological tests] (McKhann et al, 2011)

  • We conducted the Montreal Cognitive Assessment (MoCA) test at the time of recruitment to (1) eliminate any potential time gap between cognitive and ocular assessments and (2) facilitate a standard screening metric for the cognition status that could be used in the analysis independently of the subjects’ CI causation or duration

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Summary

Introduction

The impending growth in the number of people living with dementia will place significantly higher demands on both national and international healthcare (Hampel et al, 2018). A significant undertaking to prevent AD expression in individuals at high risk is identifying such persons who will eventually show the disease long before the early symptoms appear (Hampel et al, 2018). Current procedures such as magnetic resonance imaging (MRI), positron emission tomography (PET), and protein levels (e.g., tau and β amyloid) derived from cerebrospinal fluid (CSF) sampling tests are very costly and very invasive. There is a pressing need to identify early cognitive function changes that may precede symptom onset and predict eventual cognitive decline

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