Retinal vascular changes are associated with PET-based biomarkers of Alzheimer's disease: A pilot study

Retina is a non-invasive channel for assessing changes in brain microvasculature, which has been implicated in the pathophysiology of Alzheimer's disease (AD). Previous studies revealed significant relationship between clinically diagnosed AD and retinal vasculature. However, clinical diagnosis has limited sensitivity and specificity, and those investigations were conducted from traditional retinal fundus photographs which only captured a narrow section of the fundus.

Determining changes in retinal vasculature from larger area of retina between subjects with positron emission tomography (PET) biomarker-confirmed AD compared to controls.

Participants were recruited from the community and cognitive disorder clinics. Diagnosis of AD was confirmed by significant amyloid-β (Aβ) and tau uptake on PET scan. Retinal vasculature was imaged with ultra-widefield (UWF) scanning laser ophthalmoscopy and a series of vessel parameters were quantified using the semi-automated Singapore I Vessel Assessment (SIVA) software. Statistical analyses were adjusted for age, gender and systolic blood pressure. In addition, arteriole parameters were adjusted against the same measurements in venules, and vice versa.

Out of the 39 patients, 18 had radiologically confirmed AD. These individuals with AD showed significantly smaller arteriolar fractal dimension (p = 0.032) in UWF images and greater venular tortuosity (p = 0.011) in standard fundus images compared with controls. Presence of significant Aβ and tau burden was associated with lower arteriolar caliber (OR 3.857; 95% CI 1.014-14.67; p = 0.048).

Reduction of fractal dimension in retinal arterioles observed in UWF imaging is associated with cerebral Aβ and tau burden in people with biomarker-confirmed AD. Wide field retinal imaging provides an alternative perspective in demonstrating microvascular alterations related to AD in this pilot study.