ELECTRORETINOGRAPHY IN PRE-CLINICAL ALZHEIMER’S DISEASE: AN ELECTROPHYSIOLOGIC ASSESSMENT OF THE RETINA AS AN EARLY DETECTION OCULAR BIOMARKER IN VIVO

Preclinical Alzheimer's Disease (AD) describes cognitively healthy adults with positive AD pathology on cerebrospinal fluid (CSF). Previous studies have shown retinal ganglion cell (RGC) abnormalities in the early stages of AD using electroretinography (ERG). The present study uses electroretinography in preclinical AD to detect RGC function prior to the onset of dementia. We prospectively enrolled 15 adult participants (30 eyes) with preclinical AD (mean age: 75.2 ± 8.4 years) and 15 control participants (30 eyes) (mean age: 74.1 ± 7.9 years; p=0.5), classified after medical, neuropsychological, ophthalmic and CSF Ab42/pTau ratio examination. Standard Pattern Electroretinogram (PERG), standard full-field ERG (ffERG), and photopic negative response (PhNR) were performed. The corresponding wave amplitudes were measured and compared to normal healthy controls. Recorded data were statistically analyzed using Welch's t-test. PERG and PhNR detected RGC dysfunction in preclinical AD relative to controls. In PERG examination, an overall 21% N95 amplitude reduction were observed in preclinical AD (-4.90±1.80) relative to controls (-6.05±0.943, p < 0.04). Mean full-field PhNR amplitudes were significantly attenuated by 47% in preclinical AD (-23.9±14.7) compared to controls (-38.8±17.7, p < 0.03). Scotopic and photopic standard ffERG showed no significant difference between preclinical AD and controls (p > 0.05). The present study demonstrated RGC dysfunction in patients with preclinical AD as measured by PERG and PhNR. Our findings suggest that electroretinography may serve as a feasible and non-invasive means of assessing AD prior to the onset of cognitive deficits, which may be used in conjunction with other validated retinal and neurological biomarkers as outcome measures for candidate treatments.