Changes in visual function and retinal structure in the progression of Alzheimer's disease

Abstract

Background Alzheimer’s Disease (AD) can cause degeneration in the retina and optic nerve either directly, as a result of amyloid beta deposits, or secondarily, as a result of the degradation of the visual cortex. These effects raise the possibility that tracking ophthalmologic changes in the retina can be used to assess neurodegeneration in AD. This study aimed to detect retinal changes and associated functional changes in three groups of patients consisting of AD patients with mild disease, AD patients with moderate disease and healthy controls by using non-invasive psychophysical ophthalmological tests and optical coherence tomography (OCT). Methods We included 39 patients with mild AD, 21 patients with moderate AD and 40 age-matched healthy controls. Both patients and controls were ophthalmologically healthy. Visual acuity, contrast sensitivity, colour perception, visual integration, and choroidal thicknesses were measured. In addition, OCT and OCT angiography (OCTA) were applied. Findings Visual acuity, contrast sensitivity, colour perception, and visual integration were significantly lower in AD patients than in healthy controls. Compared to healthy controls, macular thinning in the central region was significant in the mild AD patients, while macular thickening in the central region was found in the moderate AD group. The analysis of macular layers revealed significant thinning of the retinal nerve fibre layer, the ganglion cell layer and the outer plexiform layer in AD patients relative to controls. Conversely, significant thickening was observed in the outer nuclear layer of the patients. However, mild AD was associated with significant thinning of the subfovea and the nasal and inferior sectors of the choroid. Significant superonasal and inferotemporal peripapillary thinning was observed in patients with moderate disease. Conclusions The first changes in the mild AD patients appear in the psychophysical tests and in the central macula with a decrease in the central retinal thickness. When there was a disease progression to moderate AD, psychophysical tests remained stable with respect to the decrease in mild AD, but significant thinning in the peripapillary retina and thickening in the central retina appeared. The presence of AD is best indicated based on contrast sensitivity.

Microglial Activation in the Retina of a Triple-Transgenic Alzheimer’s Disease Mouse Model (3xTg-AD)

“…Cell displacement and process reorientation towards an injury site are early features of microglial activation [44,45]. The microglial soma displacement towards the nuclear layers could explain the thickening in some areas of the retinal nuclear layers and the parallel thinning in plexiform layers observed by OCT using a new method for the segmentation of retinal layers in patients with mild AD [11,46]. In addition, it has been postulated that the vertical arrangement of microglial cells, like that of Müller cells, could assist in the distribution of signaling between different microglial plexuses to communicate to the rest of the retina where damage has occurred [6,47].…”

Macular Thickness Decrease in Asymptomatic Subjects at High Genetic Risk of Developing Alzheimer’s Disease: An OCT Study

“…These changes, which were reported in previous studies, suggested that changes in the RNFL thickness could be used as an early marker of AD-related brain atrophy [ 27 , 36 ]. In addition, a decrease in pRNFL thickness has been correlated with impaired cognition during disease progression [ 37 , 38 , 39 , 40 ]. This pRNFL decrease was confirmed as a potential biomarker for predicting cognitive decline in older adults during preclinical dementia [ 36 ].…”

“…In patients with established AD, a reduction in mRNFL thickness has been demonstrated in different sectors [ 37 , 41 , 42 , 43 ]. The difference between the inclusion criteria of these patients, in relation to the MMSE, makes the classification of the different stages of AD not equivalent.…”

Characteristics of Normal-tension Glaucoma Patients with Temporal Retinal Nerve Fibre Defects

“…Previous studies have analysed that superior macular damage tends to combine the visual field defect closer to fixation 13,30 . Some studies have reported that Alzheimer's disease is related to the optic nerve and the inner layers of the central macular area damages [31][32][33] . However, we excluded patients with Alzheimer's disease and other neurodegenerative diseases like cognitive decline and sensorineural hearing loss from this study in order to eliminate potential bias.…”