Retinal capillary perfusion in autosomal dominant Alzheimer's disease: Biomarkers: Searching for Alzheimer's through the eyes. (7th December 2020) - Singer, Maxwell
Abstract: Background: Alterations of perfusion in small blood vessels may be early events during Alzheimer's disease (AD) development and such differences may be visible in the retina. The purpose of the current study is to quantify retinal capillary density and blood flow in subjects with autosomal dominant Alzheimer's Disease (ADAD)‐causing mutations during the preclinical and clinical disease stages using optical coherence tomography angiography (OCTA). Method: This is a cross‐sectional study of subjects with PSEN1 or APP mutations (n = 12) and age‐matched controls (n = 21). Mutation carriers were split into early‐stage (ES) and late‐stage (LS) groups based on an age‐adjusted cutoff of ‐4 (four years before predicted age of dementia onset based on mutation variant). Each subject underwent OCTA imaging of the central 3x3mm macula. Capillary density was measured using previously validated custom software and quantified as vessel skeleton density or VSD. Capillary blood flow was measured using a novel metric called flux which is derived from non‐binarized OCTA images and represents total number of red blood cells passing through the voxel per unit time. Statistical analysis was performed using generalized estimating equations adjusting for gender and correlation of two eyes from the same subject. Result: ES carriers (n = 4, 3 w/CDR = 1, 1 w/CDR = 0.5) had a significantly greater flux (0.161 ± 0.006) than controls (n = 21, 0.144 ± 0.01, p = 0.02) and LS carriers (n = 12, CDR scores 0.5 – 3, 0.144 ± 0.008, p<0.0001, Figure 1). In contrast, there was no difference between flux of LS carriers and controls. ES carriers also had significantly greater capillary density (VSD) than controls (0.157 ± 0.006 vs 0.153 ± 0.005; p = 0.017). Conclusion: ES carriers of PSEN1 or APP mutations demonstrate increased retinal capillary blood flow when compared to controls that was not present in LS carriers. Our data suggests that there is increased retinal perfusion in ES carriers, possibly resulting from increased blood flow in perfused capillary segments and recruitment of dormant capillary segments. These findings are consistent with studies showing cerebral hyperperfusion in pre‐symptomatic individuals with ADAD and indicate this may extend to the retina.