Reduced Retinal Perfusion With Preserved Microvascular Network Density in Early Alzheimer's Disease: A Multimodal Imaging Study.

PURPOSE: To characterize retinal neurovascular alterations in Alzheimer's disease (AD) and mild cognitive impairment (MCI) and examine structure-function relationships. METHODS: Eighty-two participants (28 with AD, 21 with MCI, and 33 cognitively normal controls) underwent retinal imaging. Retinal blood flow (RBF) was measured using a function imager. Retinal vessel density (RVD), retinal vessel length density (RVLD), vessel width, and capillary perfusion density (CPD) were quantified with optical coherence tomography (OCT) angiography and retinal tissue volume (RTV) with ultra-high-resolution OCT. Derived metrics included retinal tissue perfusion (RTP), retinal capillary flow index (RCF), and volumetric vessel density. Group comparisons and age-adjusted correlations were performed. RESULTS: Compared with controls, the combined AD + MCI group had significantly lower RBF (3.18 ± 1.02 vs. 4.22 ± 0.79 nL/s; P < 0.001), RCF (0.21 ± 0.07 vs. 0.26 ± 0.04 nL/s/mm; P < 0.001), and RTP (2.89 ± 0.94 vs. 3.86 ± 0.77 nL/s/mm3; P < 0.001). Morphometric indices of the perfused capillary network and retinal tissue volume (RVD, RVLD, CPD, vessel width, RTV) did not differ (all P > 0.05). In AD + MCI, RBF was not associated with structural or morphometric microvascular metrics, whereas controls exhibited age-adjusted correlations between RBF and vessel density and length density. CONCLUSIONS: AD and MCI are characterized by reduced retinal perfusion and capillary flow index despite preserved network density and retinal tissue volume, suggesting altered retinal hemodynamic-morphometric relationships. TRANSLATIONAL RELEVANCE: Hemodynamic retinal imaging detects early perfusion impairment in AD and MCI before changes in microvascular network density or retinal tissue volume, offering a noninvasive biomarker for detection and therapeutic monitoring.