Association found between laminar thinning and poor cognitive function

I learned in school that the eyes can be like water from the well with respect to systemic health. I think I was a third-year student when I had the “a-ha” moment that patients with diabetes and retinopathy don’t have vascular compromise just in their eyes. It is going on elsewhere, but the eyes are the only place doctors are able to see it noninvasively.

The same could be said for uveitis, arthritis, thyroid disease, and so on. With this in mind, it should come as no surprise that glaucoma, as a progressive neurodegenerative disease, has been seen as perhaps having an association with other progressive neurodegenerative diseases.

A paper recently published in Translational Vision Science and Technology explores this very possibility.¹ In the study, the authors set out to explore one aspect of glaucoma, lamina cribrosa thickness, and to determine if laminar thickness has any relationship to cognitive function.

Lamina cribrosa study

The study consisted of 105 participants with primary open-angle glaucoma (POAG) and 23 controls. The mean ages of the 2 study groups were 72.2 and 74.9, respectively. The relationship of females to males in the POAG group was 48 to 57. For the control group, it was 7 to 16.

High myopes and high hyperopes (>-8.00 D and +4.00 D, respectively) were excluded. Patients with astigmatism of >3.00 D were also excluded. Patients with potentially confounding eye disease were also excluded.

Of note, the definition of POAG for the purposes of this study was defined as open angles, optic nerve/retinal nerve fiber damage, and a visual field defect. So, glaucoma had to be perimetric for this study.

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Lamina cribrosa thickness was measured by spectral domain optical coherence tomography (SD-OCT) with enhanced depth imaging (EDI). It was defined at 3 different locations within the lamina cribrosa itself (superior midperipheral, mid-horizontal, and inferior midperipheral). A mean laminar thickness was also calculated.

As for neuropsychological assessments, a comprehensive battery of 15 tests, including the Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Assessment Battery (CERAD-K-N), was used in order to evaluate and grade cognitive function. The CERAD-K-N consists of 9 separate cognitive tests. The 15 tests administered gave cognitive function scores based on 8 different aspects of cognitive function: global cognition, attention/concentration, language, visuospatial function, verbal memory, visual memory, frontal function, and depression.

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Results

The results of the study were intriguing. Investigators found a significant association between laminar thinning and poorer quality of cognitive function. This relationship did not depend upon glaucoma severity, and it is suggestive of a possible common mechanism between glaucoma and impaired cognition. Therefore, thinning of the lamina cribrosa could be some sort of biomarker for cognitive impairment, or possibly the risk thereof.

If this is true, then why? The investigators point to a previous finding that is suggestive of an abnormal cerebrospinal fluid (CSF) protein which is associated with laminar thinning in patients with and without Alzheimer’s disease.²

The potential connection between glaucoma and impaired cognitive function, as determined by this study through the shared aspect of laminar thinning, could point to a common pathological change in the tissues of the brain and those of the lamina cribrosa. The investigators suggest astrocytes, which play a role in making up the scaffolding of the central nervous system, as a possible explanation of this supposed connection. These cells help to maintain the structural integrity of the lamina cribrosa. They also have a relationship with retinal vasculature, just as they do vasculature within the brain and therefore may play an important role in retinal and cerebral blood flow regulation.

Study limitations

This study did have several limitations. The sample size is relatively small, and further research with larger cohorts of patients is needed to validate the results of this study. As well, other aspects of the optic nerve head were not included in the study’s design—just the thickness of the lamina cribrosa at 3 different anatomical points. Participants in the glaucoma wing of the study were required to have visual field defects in order to be included. Could the inclusion of so-called “pre-perimetric” glaucoma patients (those with clear visual field studies) have perhaps shed more light on the possibility of a linear relationship between glaucoma and cognitive impairment?

Whatever the link may be, it is important for clinicians to not lose sight of the fact that the eyes are not separate from the central nervous system (or the rest of the body), but as hybrid organs in a sense, they contain a portion of the central nervous system by housing the terminal aspects of the optic nerve.

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References

1. Lee SH, Han JW, Lee EJ, Kim TW, Kim H, Kim KW. Cognitive Impairment and Lamina Cribrosa Thickness in Primary Open-Angle Glaucoma [published correction appears in Transl Vis Sci Technol. 2020 Sep 21;9(10):19]. Transl Vis Sci Technol. 2020;9(7):17.

2. Lee EJ, Kim TW, Lee DS, Kim H, Park YH, Kim J, Lee JW, Kim S. Increased CSF tau level is correlated with decreased lamina cribrosa thickness. Alzheimers Res Ther. 2016;8:6.