Retinal vascular and structural changes are associated with amyloid burden in the elderly: ophthalmic biomarkers of preclinical Alzheimer’s disease

Abstract

BackgroundRetinal imaging may serve as an alternative approach to monitor brain pathology in Alzheimer’s disease (AD). In this study, we investigated the association between retinal vascular and structural changes and cerebral amyloid-β (Aβ) plaque load in an elderly cohort.MethodsWe studied a total of 101 participants, including 73 elderly subjects (79 ± 5 years, 22 male) with no clinical diagnosis of AD but reporting some subjective memory change and an additional 28 subjects (70 ± 9 years, 16 male) with clinically established AD. Following a complete dilated ocular examination, the amplitude of retinal vascular pulsations and dynamic response, retinal nerve fibre layer thickness and retinal ganglion cell layer (RGCL) thickness were determined in all patients. Systemic blood pressure and carotid-to-femoral pulse wave velocity were measured. The elderly cohort also underwent magnetic resonance imaging and 18F-florbetaben (FBB)-positron emission tomographic amyloid imaging to measure neocortical Aβ standardised uptake value ratio (SUVR), and this was used to characterise a ‘preclinical’ group (SUVR >1.4).ResultsThe mean FBB neocortical SUVR was 1.35 ± 0.3. The amplitude of retinal venous pulsations correlated negatively with the neocortical Aβ scores (p < 0.001), whereas the amplitude of retinal arterial pulsations correlated positively with neocortical Aβ scores (p < 0.01). RGCL thickness was significantly lower in the clinical AD group (p < 0.05).ConclusionsThe correlation between retinal vascular changes and Aβ plaque load supports the possibility of a vascular component to AD. Dynamic retinal vascular parameters may provide an additional inexpensive tool to aid in the preclinical assessment of AD.

Retinal analysis of a mouse model of Alzheimer’s disease with multicontrast optical coherence tomography

“…However the question still remains whether the retina can hold the key to early AD diagnosis as there are few studies which directly correlate findings in the retina to those in the brain. Those studies which have been done before have found a correlation between the amplitude of retinal vascular pulsatility and neocortical Aβ scores (measured using florbetaben positron emission tomography), 6 and also between fluorescent components (measured using fluorescence lifetime imaging ophthalmoscopy) and both p-tau181-protein concentration in the cerebral spine fluid and the mini-mental state examination score. 7 Recent studies have also focused on the identification of extracellular Aβ accumulations in the retina of AD patients, however there are conflicting reports on this topic.…”

Microglia control vascular architecture via a TGFβ1 dependent paracrine mechanism linked to tissue mechanics

“…While the role of these interactions has been demonstrated in cell differentiation and malignancies, very little is known about it in the central nervous system (CNS) because of its complex cellular composition and mechanical heterogeneity 2,3 . Thinning of retinal layers in Alzheimer's patients 4 alters retinal stiffness and correlates with the changes in microvasculature that mirror pathological processes in the brain 5 ; CNS scarring and neurodegeneration are accompanied by similar changes [6][7][8] . Compared with other tissues, the retina seems to be particularly affected by a plethora of mechanical stimuli arising from eye movements and changes in intraocular pressure.…”

Comparison of Retinal Microvasculature in Patients With Alzheimer's Disease and Primary Open-Angle Glaucoma by Optical Coherence Tomography Angiography

“…11 A potential relationship between deposition of abnormal Ab in the vicinity of vessels and the disturbance of the blood flow, as well as the diameter of retinal vessels, has been identified in AD patients. [12][13][14] The pathologic mechanism underlying primary open-angle glaucoma (POAG) involves apoptosis of retinal ganglion cells (RGCs) and gradual decrease in thicknesses of both pRNFL and the retinal ganglion cell layer (GCL). 15 In addition to increased intraocular pressure (IOP), vascular mechanisms play an important role in this process.…”