Retinal tissue hypoperfusion in patients with clinical Alzheimer’s disease

Abstract

Background: It remains unknow whether retinal tissue perfusion occurs in patients with Alzheimer’s disease. The goal was to determine retinal tissue perfusion in patients with clinical Alzheimer’s disease (CAD). Methods: Twenty-four CAD patients and 19 cognitively normal (CN) age-matched controls were recruited. A retinal function imager (RFI, Optical Imaging Ltd., Rehovot, Israel) was used to measure the retinal blood flow supplying the macular area of a diameter of 2.5 mm centered on the fovea. Blood flow volumes of arterioles (entering the macular region) and venules (exiting the macular region) of the supplied area were calculated. Macular blood flow was calculated as the average of arteriolar and venular flow volumes. Custom ultra-high-resolution optical coherence tomography (UHR–OCT) was used to calculate macular tissue volume. Automated segmentation software (Orion, Voxeleron LLC, Pleasanton, CA) was used to segment six intra-retinal layers in the 2.5 mm (diameter) area centered on the fovea. The inner retina (containing vessel network), including retinal nerve fiber layer (RNFL), ganglion cell-inner plexiform layer (GCIPL), inner nuclear layer (INL) and outer plexiform layer (OPL), was segmented and tissue volume was calculated. Perfusion was calculated as the flow divided by the tissue volume. Results: The tissue perfusion in CAD patients was 2.58 ± 0.79 nl/s/mm3 (mean ± standard deviation) and was significantly lower than in CN subjects (3.62 ± 0.44 nl/s/mm3, P < 0.01), reflecting a decrease of 29%. The flow volume was 2.82 ± 0.92 nl/s in CAD patients, which was 31% lower than in CN subjects (4.09 ± 0.46 nl/s, P < 0.01). GCIPL tissue volume was 0.47 ± 0.04 mm3 in CAD patients and 6% lower than CN subjects (0.50 ± 0.05 mm3, P < 0.05). No other significant alterations were found in the intra-retinal layers between CAD and CN participants. Conclusions: This study is the first to show decreased retinal tissue perfusion that may be indicative of diminished tissue metabolic activity in patients with clinical Alzheimer’s disease.