Abstract
Purpose :
Retinal degeneration occurs in Alzheimer's disease (AD), but its temporal association with intracranial pathology is unknown. This study investigated the association between OCT-derived retinal layer thickness and intracranial diffusion tensor imaging (DTI) measures of optic tracts among subjects with an Autosomal Dominantly inherited form of AD (ADAD).
Methods :
Carriers of ADAD mutations (A431E_PSEN1 or V171I_APP or F388S_PSEN1) or non-carriers of the mutation from the same family were recruited from an NIH funded longitudinal study of ADAD. Outer nuclear layer (ONL), Ganglion Cell Layer (GCL), Inner Plexiform Layer (IPL) and GCIPL thickness were obtained using SD-OCT (Heidelberg Spectralis). The retinotopically mapped white matter tract integrity was measured along the optic tracts using previously described DTI measures including fractional anisotropy (FA), radial diffusivity (RD), mean diffusivity (MD), axial diffusivity (AD). The correlation between the retinal layer thickness and the DTI measures was assessed using generalized estimating equations to adjust for correlation between retinal measurements from two eyes of the same subject.
Results :
Fifteen subjects with ADAD mutations (9 males, mean age 36yrs) and 4 non-carriers (1 male, mean age 37yrs) were recruited into the study. Six subjects with ADAD mutations were asymptomatic. FA was positively correlated with GCL (β=0.0017, P=0.01) and GCIPL complex (β=0.0008, P=0.03) thickness. RD was negatively correlated with GCL (β=-0.0105, P=0.002) and GCIPL complex (β=-0.0071, P=0.001) thickness. MD was negatively correlated with GCIPL complex (P=0.001) thickness. AD was positively correlated with GCL and GCIPL complex but not significant (P>0.05). The correlations between ONL thickness and DTI measures (FA, MD, AD and RD) were not significant (P>0.05).
Conclusions :
GCIPL thickness was significantly associated with DTI measures of optic tract integrity. These findings support the hypothesis that the degeneration of ganglion cells in the retina is concurrent with a decrease in white matter integrity of the optic tracts in ADAD. The causal chain of events is a topic of further investigation.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.