Relation between retinal morphology, visual pathway integrity and plasmatic amyloid beta 42 peptide in old and young beagles

Sammanfattning: The spontaneously occurring behavioural syndrome referred to as canine cognitive dysfunction (CCD) is considered the canine counterpart of Alzheimer’s disease (AD). Changes in the retina such as nerve fibre layer (NFL) and ganglion cell complex (GCC) thinning have been observed in Alzheimer’s patients. There is also evidence that visual evoked potentials (VEPs) time-to-peaks are delayed in human patients, raising the question if those changes can also be observed in dogs. The aim of this study was to measure NFL and GCC using optical coherence tomography (OCT), as well as record VEPs in young and old dogs to investigate age related changes in those tests, as well as to stablish a correlation to their amyloid beta (Aβ) peptide levels, for in further studies add clinical, behavioural and necropsy information to evaluate the use of those tests in identifying cognitive impairment. Flash-VEP recordings and OCT scans of the foveal/parafoveal and peripapillary regions were conducted in a group of 12 beagles (6 young, 6 geriatric). An ELISA quantification of Aβ 42 was done with plasma samples from these dogs. No effect of age on Aβ 42 concentration was found in our samples (p=0.93) making identification of cognitively impaired individuals based only on Aβ 42 not possible. Age had a significant effect on GCC in the parafoveal and peripapillary regions (p=0.03 and p=0.04) and on NFL in the parafoveal region (p=0.02). Thinning of GCC and NFL in different parafoveal regions was associated with lower Aβ 42 values and thinning of foveal NFL with increased values. Age had a significant effect on most of the late VEP components. Delayed P2 and P4 time-to-peaks were associated with increased and decreased Aβ 42 respectively. We found that GCC thickness was a more straight-forward and robust measurement than the NFL and it has previously been reported to provide further information about synaptic density as it includes the inner plexiform layer and synapses between the ganglion and the bipolar cells. There was a considerable loss of peripapillary measurements for both GCC and NFL thickness and we consider that the distortion caused by vessels in this region in the dog makes it less suitable for measurements of layer thickness. The age-related changes previously described for OCTs and VEPs in dogs were observed also in this study. OCT-imaging and flash-VEP can readily be done in dogs and may provide additional information relevant for assessing of cognitive function in aging dogs. However, a multimodal approach seems to be unavoidable to determine if retinal morphology and functional testing of the visual pathways can be used as markers for CCD.