Association found between macular retinal nerve fiber layer thickness, cognitive decline

Dilraj Grewal, MD, MBBS

The authors measured retinal nerve fiber layer (RNFL) thickness in the macula (compared with the conventionally measured peripapillary RNFL thickness) using OCT in 430 Korean participants aged 60 years or older and found that macular RNFL thickness correlates with decline in cognitive function scores, with thinner RNFL being associated with a larger cognitive decline. The study had a cross-sectional and longitudinal component over a mean follow-up of 5.4 years, and there was no correlation between RNFL thickness and cognitive function in the longitudinal study. In addition, when the study authors looked at data based on quartiles, the lowest quartile group showed a much higher rate of mild cognitive impairment and Alzheimer’s disease prevalence than the other quartiles.

This is an important study because we often do not use macular RNFL thickness in practice, and this may be an additional biomarker that is associated with neuropsychiatric test scores and may help predict cognitive decline. There is some thought that macular RNFL thinning may precede peripapillary RNFL thinning. The association that individuals with a thinner baseline macular RNFL were likely to experience a greater degree of cognitive decline leading to cognitive impairment is important, and the authors controlled for several covariates including age, sex, level of education, presence of APOE e4 allele, diabetes and hypertension. Due to the inherent challenges in validating biomarkers in diseases such as mild cognitive impairment and Alzheimer’s disease with such a wide phenotypic spectrum, this information does not affect clinical practice immediately but rather propels our efforts forward toward developing meaningful retinal imaging biomarkers to predict cognitive decline and dementia.

While this is promising data obtained from a community-based population, additional larger, more diverse studies across multiple racial and ethnic groups and over a longer follow-up of at least 10 years are required before retinal parameters such as macular RNFL thickness can be deployed to predict cognitive decline in the real world. The longer follow-up is critical due to the long continuum in the development of cognitive impairment in mild cognitive impairment and Alzheimer’s disease. It is also important to consider dropout in such long studies, with the retention rate in this study being 50% at 5 years. In addition, the true impact of factors such as age, sex, diabetes, hypertension and APOE e4 status needs to be further elucidated. Well-designed prospective clinical studies with biomarker-defined populations are key to achieve the goal of having a robust retinal imaging-based biomarker for neurodegenerative diseases.