BACKGROUD AND OBJECTIVE: To evaluate the relationship between retinal microvascular parameters on optical coherence tomography angiography (OCTA) and neurodegenerative changes assessed by measurement of brain volume on volumetric magnetic resonance imaging (MRI) in Alzheimer's disease (AD) and mild cognitive impairment (MCI). PATIENTS AND METHODS: Sixteen subjects with AD and MCI underwent OCTA imaging (3 mm × 3 mm and 6 mm × 6 mm scans) and volumetric brain MRI imaging with automated volumetric segmentation and quantification. Spearman's correlation (ρ) was performed between forebrain parenchyma, cortical gray matter, inferolateral ventricle (ILV), lateral ventricle (LV), and hippocampus (HP) MRI volumes and vessel density (VD), along with perfusion density (PD) for the 6-mm circle, 6-mm ring, 3-mm circle, and 3-mm ring Early Treatment Diabetic Retinopathy Study regions of the superficial capillary plexus. RESULTS: Thirty eyes of 16 patients (seven MCI and nine AD) with good-quality OCTA images were analyzed. ILV volume inversely correlated with the VD in the 6-mm circle (ρ = -0 .565, P = .028) and 3-mm ring (ρ = -0.569, P = .027) and PD in the 3-mm ring (ρ = -0.605, P = .0169). Forebrain, cortical gray matter, LV, and HP volumes did not significantly correlate with either VD or PD (P > .05). CONCLUSIONS: In this pilot investigation, the authors found a significant correlation between reduction in the superficial capillary plexus VD and PD on OCTA and expansion of the ILV in MCI and AD. This relationship between the retinal microvasculature and cerebral volumetric changes deserves further investigation. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:709-718.].