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

Background: Retinal 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-beta (A beta) plaque load in an elderly cohort. Methods: We 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 F-18-florbetaben (FBB)-positron emission tomographic amyloid imaging to measure neocortical A beta standardised uptake value ratio (SUVR), and this was used to characterise a 'preclinical' group (SUVR > 1.4). Results: The mean FBB neocortical SUVR was 1.35 +/- 0.3. The amplitude of retinal venous pulsations correlated negatively with the neocortical A beta scores (p < 0.001), whereas the amplitude of retinal arterial pulsations correlated positively with neocortical A beta scores (p < 0.01). RGCL thickness was significantly lower in the clinical AD group (p < 0.05). Conclusions: The correlation between retinal vascular changes and A beta 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.