Abstract
Purpose :
Retinal imaging provides a potential means to detect early cognitive decline noninvasively. In this study, we measure photoreceptor layer thicknesses using optical coherence tomography (OCT) to evaluate for associations between photoreceptor structure and cognitive function.
Methods :
We obtained macular OCT volume scans of eyes from adult rhesus macaques and performed image segmentation using a custom, graph-based segmentation software (DOCTRAP) to measure outer nuclear layer (ONL), inner segment (IS), and outer segment (OS) thicknesses within different circular regions (1mm fovea, 3mm parafovea, and 6mm macula) centered on the fovea of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid. Animals underwent a series of standardized biobehavioral assessments including “rational” decision-making, working memory, and sequence memory, as well as measurement of visual acuity at 2m, 1m, and 0.33m. Relations between cognitive tests and retinal layers were assessed by multiple stepwise regression, adjusted for age, testing condition, and visual acuity.
Results :
We evaluated 90 rhesus macaques (mean age of 19.86 years, standard deviation +/- 3.28) with OCT imaging and cognitive evaluations. Older age was associated with photoreceptor IS thinning within the central foveal and parafoveal region (-0.26 mm/year, p = 0.03) or macula (-0.36 mm/year, p = 0.009), while ONL and OS layers remained mostly unchanged. Animals with thinner macular IS layers showed more variability in decision-making reaction time across multiple trials (F(1,88) = 4.699, p =.035, adjusted R2 = .07) and poorer working memory, (F(1,88) = 4.567, p = .046, adjusted R2 = .151) when adjusted for age, testing condition, and visual acuity. Neither ONL nor OS layer thicknesses were associated with cognitive behavioral test performance.
Conclusions :
Photoreceptor layer thinning may be associated with cognitive decline in non-human primates and may serve as an imaging biomarker for cognitive function in preclinical research using non-human primates.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.