Retinal Data Detect Alzheimer Disease Biomarker Before Cognitive Decline

Researchers discovered retinal data can predict which individuals have cerebrospinal fluid (CSF) biomarkers of Alzheimer disease (AD) pathology before cognitive decline is detectable, according to a study published in PLOS One.

Currently, more than 26 million people are affected by AD worldwide, while in 2019, the disease accounted for $290 billion in medical costs in the United States. It is estimated the prevalence of AD will quadruple by 2050. To diagnose early disease stages and allow therapy trials before symptomatic decline, widespread screening approaches are urgently needed, the authors argued.

Pathology of AD precedes symptom onset, researchers explained. “Since the retinal nerve fiber layer (RNFL) is depleted in established AD, we tested whether its thickness can predict whether cognitively healthy (CH) individuals have a normal or pathological CSF Aß₄₂ (A) and tau (T) ratio.” In addition, visual dysfunctions in AD have been associated with degeneration of the optic nerve and retina and developmental outgrowths of the brain.

Using a logistic regression model, investigators separated a CH group into 2 subgroups, normal (CH-NAT, n = 16) or pathological (CH-PAT, n = 27). Mean age of CH-PAT was 75.2 (SD 8.4) years while the cohort was 48% female. In comparison, mean age of CH-NAT was 74.1 (7.4) years, and the group was 56% female.

Both test groups were “cognitively healthy as defined after detailed neuropsychiatric testing and were biochemically differentiated based on cutoff levels that are established in AD for CSF Aß₄₂ and total tau biomarkers,” the authors noted.

To assess RNFL, ganglion cell-inner plexiform layer (GC-IPL), and macular thickness, researchers used spectral-domain optical coherence tomography (OCT).

Data revealed:

• Mean RNFL was thinner in the CH-PAT group by 9.8 (2.7) μm (P <.001)
• The difference between groups in mean RNFL thinning was significant at the nasal location
• The CSF Aß₄₂/ Tau ratio was more correlated with RNFL thinning compared to individual biomarkers
• The CSF total Tau levels correlate more with RNFL thinning than Aß₄₂
• RNFL thickness classified CH-NAT vs. CH-PAT with 87% sensitivity and 56.3% specificity

Overall, the researchers found “RNFL thickness measure by OCT was able to predict the biochemical class of CH-NAT vs. CH-PAT in cognitively healthy, older individuals with high sensitivity.” The study was the first of its kind to predict presymptomatic AD pathology using noninvasive technology with high sensitivity. It is also the largest study of RNFL measured by OCT in preclinical AD.

Future studies ought to include different populations to assess neurological and ophthalmological disease, physiological and cultural/ethnic specificity, the researchers noted. They are also in the process of developing a balanced cut-off to maximize sensitivity and specificity.

“OCT measurements have the immediate potential to allow rapid data acquisition in studies of AD patients or those at risk for AD with the objective of building a large database of RNFL thickness in different AD patient populations,” the authors concluded.

Reference:

Asanad S, Fantini M, Sultan W, et al. Retinal nerve fiber layer thickness predicts CSF amyloid/tau before cognitive decline. PLoS One. Published online May 29, 2020. doi:10.1371/journal.pone.0232785