Association of Retinal Nerve Fiber Layer Thinning With Current and Future Cognitive Decline

Abstract

Identifing potential screening tests for future cognitive decline is a priority for developing treatments for and the prevention of dementia. OBJECTIVE To examine the potential of retinal nerve fiber layer (RNFL) thickness measurement in identifying those at greater risk of cognitive decline in a large community cohort of healthy people. DESIGN, SETTING, AND PARTICIPANTS UK Biobank is a prospective, multicenter, community-based study of UK residents aged 40 to 69 years at enrollment who underwent baseline retinal optical coherence tomography imaging, a physical examination, and a questionnaire. The pilot study phase was conducted from March 2006 to June 2006, and the main cohort underwent examination for baseline measures from April 2007 to October 2010. Four basic cognitive tests were performed at baseline, which were then repeated in a subset of participants approximately 3 years later. We analyzed eyes with high-quality optical coherence tomography images, excluding those with eye disease or vision loss, a history of ocular or neurological disease, or diabetes. We explored associations between RNFL thickness and cognitive function using multivariable logistic regression modeling to control for demographic as well as physiologic and ocular variation. MAIN OUTCOMES AND MEASURES Odds ratios (ORs) for cognitive performance in the lowest fifth percentile in at least 2 of 4 cognitive tests at baseline, or worsening results on at least 1 cognitive test at follow-up. These analyses were adjusted for age, sex, race/ethnicity, height, refraction, intraocular pressure, education, and socioeconomic status. RESULTS A total of 32 038 people were included at baseline testing, for whom the mean age was 56.0 years and of whom 17 172 (53.6%) were women. A thinner RNFL was associated with worse cognitive performance on baseline assessment. A multivariable regression controlling for potential confounders showed that those in the thinnest quintile of RNFL were 11% more likely to fail at least 1 cognitive test (95% CI, 2.0%-2.1%; P = .01). Follow-up cognitive tests were performed for 1251 participants (3.9%). Participants with an RNFL thickness in the 2 thinnest quintiles were almost twice as likely to have at least 1 test score be worse at follow-up cognitive testing (quintile 1: OR, 1.92; 95% CI, 1.29-2.85; P < .001; quintile 2: OR, 2.08; 95% CI, 1.40-3.08; P < .001). CONCLUSIONS AND RELEVANCE A thinner RNFL is associated with worse cognitive function in individuals without a neurodegenerative disease as well as greater likelihood of future cognitive decline. This preclinical observation has implications for future research, prevention, and treatment of dementia.

Visual tests predict dementia risk in Parkinson disease

“…In the wider population, RNFL thinning is linked with higher rates of cognitive decline, 7 and another study found that GC-IPL thinning (but not RNFL) is linked with prevalent dementia. 8 Our finding of a link between retinal thinning and risk of dementia may not be wholly specific to Parkinson dementia and may also apply to other types of dementia.…”

“…Retinal structure can be imaged noninvasively using optical coherence tomography (OCT) 4 and shows thinning in Alzheimer disease 5 and as a population screen for dementia. [6][7][8] Retinal structural changes are seen in PD, but early studies of retinal nerve fiber layer (RNFL) thinning in PD were not replicated. 9 The location of dopaminergic amacrine cells in the inner plexiform layer (IPL) 10 in nonhuman studies, and postmortem findings of phosphorylated alpha-synuclein in the IPL, suggest that deeper layers are more likely to be affected in PD.…”

Retinal nerve fibre changes in sports‐related repetitive traumatic brain injury

“…Recent studies have demonstrated significant RNFL thinning in collision sport athletes and Olympic boxers, however, the former study by Leong et al failed to demonstrate statistically significant RNFL thinning in subgroup analysis of American Football players. Furthermore, studies have reported that RNFL thinning in individuals without a neurodegenerative disease is associated with reduced visual acuity and worse cognitive function . RNFL thinning has also been shown to predict a greater likelihood of future cognitive decline and dementia …”

“…Furthermore, studies have reported that RNFL thinning in individuals without a neurodegenerative disease is associated with reduced visual acuity 26 and worse cognitive function. 28 RNFL thinning has also been shown to predict a greater likelihood of future cognitive decline 28 and dementia. 29 Two recent studies have demonstrated a correlation between RNFL thinning and brain atrophy as assessed on MRI.…”

Amyloid precursor protein‐mediated mitochondrial regulation and Alzheimer's disease

“…The retina, the neural layer of the eye, is a developmental extension of the brain and is the only part of the CNS that can be optically imaged in vivo . The retina manifests features of CNS diseases, and methods to detect retinal biomarkers of Alzheimer's disease are in various stages of development (Hinton et al, ; Jentsch et al, ; Koronyo et al, ; van Wijngaarden et al, ; Ko et al, ). Several imaging approaches have been postulated to measure NADH and FAD autofluorescence in vivo (Elner et al, ; Jentsch et al, ).…”