Greater Attenuation of Retinal Nerve Fiber Layer Thickness in Alzheimer's Disease Patients

Abstract

Thinning of retinal nerve fiber layer (RNFL) may reflect neurodegeneration of the central nervous system, which has been reported as part of the neuropathogenesis of Alzheimer's disease (AD). Specifically, AD patients have thinner RNFL as compared to age-matched normal controls. However, whether reduction of RNFL over time can predict those at higher risk to develop cognitive deterioration remains unknown. We therefore set out a prospective clinical investigation to determine both the reduction of RNFL thickness and the deterioration of cognitive function over a period of 25 months in 78 participants (mean age 72.31 ± 3.98 years, 52% men). The participants were categorized as stable participants whose cognitive status remained unchanged (n = 60) and converted participants whose cognitive status deteriorated, which was diagnosed by DSM-VI (for AD) and Petersen's definition (for mild cognitive impairment) (n = 18). Here we show for the first time that the converted participants had greater reduction of RNFL thickness than the stable participants. Specifically, the reduction in the thickness of the inferior quadrant RNFL in the converted participants was greater than that in stable participants [-11.0 ± 12.8 (mean ± standard deviation) μm versus 0.4 ± 15.7 μm, p = 0.009]. These data showed that greater reduction in the inferior quadrant of RNFL thickness might indicate a higher risk for the old adults to develop cognitive deterioration. These findings have established a system to embark on a larger scale study to further test whether changes in RNFL thickness can serve as a biomarker of AD.

Retinal nerve fiber layer and macular thickness in patients with schizophrenia: Influence of recent illness episodes

“…We cannot provide an explanation regarding differential effects on the quadrants, or on possible differences between the two eyes. However, previous studies in schizophrenia (Chu et al, 2012;Lee et al, 2013) as well as other neuropsychiatric disorders (Motchos et al, 2011;Kirbas et al, 2013;Shi et al, 2014) have also found differences between quadrants. In these studies several hypotheses were proposed in order to explain these differential effects, but none of them has been proven to date.…”

Retinal amyloid pathology and proof-of-concept imaging trial in Alzheimer’s disease

“…In addition to afflicting the brain, AD also affects the retina, a developmental outgrowth of the brain (12)(13)(14), possibly causing these symptoms. The retinas of AD patients display pathologies such as nerve fiber layer (NFL) thinning, retinal ganglion cell (RGC) degeneration, reduction of blood flow and vascular alterations, astrogliosis, and abnormal electroretinogram patterns (11,(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). Among the many characteristics it shares with the brain, the retina contains neurons, astroglia, microglia, microvasculature with similar morphological and physiological properties, and a blood barrier (12-14, 34, 35).…”

Glia-Mediated Retinal Neuroinflammation as a Biomarker in Alzheimer's Disease

“…There were reports demonstrating a decrease in the thickness of RNFL in AD patients [5,70,71,72,73,74,75,76], while other studies found no differences in the RNFL thickness of AD patients [77,78]. These inconsistent results might be due to the distinct evaluation techniques, as well as the evaluation criteria, such as the retinal region [73].…”