Impaired retinal microcirculation in patients with Alzheimer's disease

Hong Jiang, Yi Liu, Yantao Wei, Yingying Shi, Clinton B Wright, Xiaoyan Sun, Tatjana Rundek, Bernard S Baumel, Jonathan Landman, Jianhua Wang, Hong Jiang, Yi Liu, Yantao Wei, Yingying Shi, Clinton B Wright, Xiaoyan Sun, Tatjana Rundek, Bernard S Baumel, Jonathan Landman, Jianhua Wang

Abstract

The goal of this study was to determine the retinal blood flow rate (BFR) and blood flow velocity (BFV) of pre-capillary arterioles and post-capillary venules in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Forty patients (20 AD and 20 MCI) and 21 cognitively normal (CN) controls with a similar age range (± 5 yrs) were recruited. A retinal function imager (RFI) was used to measure BFRs and BFVs of arterioles and venules in the macular region. The thickness of the ganglion cell-inner plexiform layer (GCIPL) was measured using Zeiss Cirrus optical coherence tomography. Macular BFRs in AD group were 2.64 ± 0.20 nl/s (mean ± standard deviation) in arterioles and 2.23 ± 0.19 nl/s in venules, which were significantly lower than in MCI and CN groups (P < 0.05). In addition, BFRs in MCI were lower than in CN in both arterioles and venules (P < 0.05). The BFV of the arterioles was 3.20 ± 1.07 mm/s in AD patients, which was significantly lower than in CN controls (3.91 ± 0.77 mm/s, P = 0.01). The thicknesses of GCIPL in patients with AD and MCI were significantly lower than in CN controls (P < 0.05). Neither BFV nor BFR in arterioles and venules was related to age, GCIPL thickness, mini mental state examination (MMSE) score and disease duration in patients with AD and MCI (P > 0.05). The lower BFR in both arterioles and venules in AD and MCI patients together with the loss of GCIPL were evident, indicating the impairment of the two components in the neurovascular-hemodynamic system, which may play a role in disease progression.

Conflict of interest statement

Competing Interests: Dr. Jianhua Wang is a member of scientific advisory board of Optical Imaging Ltd. All other authors have no proprietary interest in any materials or methods. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Quantitative retinal blood flow velocity…
Fig 1. Quantitative retinal blood flow velocity map and macular blood flow.
(A) The retina of a healthy subject imaged using the RFI device with a field of view of 20-degrees (4.3 × 4.3 mm2) centered on the fovea (dark area in the center) is shown. The arterioles are marked in red and overlaid with the measured blood flow velocities (mm/s); the venules and their respective velocities are marked in pink. The measured vessels cover the second, third and fourth branches of the retinal vessels. A negative value indicates blood flow away from the heart. In this case, the arteriolar flow moved towards to the fovea. A positive value indicates blood flow towards to the heart. In this case, the vessels are venules. (B) To analyze the macular blood flow, supplying the macular region including the vascular zone of the fovea, a 2.3 mm circle (blue) centered on the fovea was drawn and vessel diameters were measured in vessels at the locations (yell and green dots) crossing the circle. The diameter of the vessels which crossed the circle was determined. Blood flow of the vessel segment was calculated using the measured velocity and diameter for each arteriole (yellow dot) or venule (green dot). The total macular flow was the sum of all flow rates in the arterioles (all yellow dots) and venules (all green dots) which crossed the circle. The total macular flow rate of this healthy subject was 3.7 nl/s in the arterioles and 3.5 nl/s in the venules. Bar = 500 μm.
Fig 2. Retinal blood flow, velocity and…
Fig 2. Retinal blood flow, velocity and vessel diameter in AD and MCI patients compared with CN controls.
(A) Total arteriolar and venular blood flow rates were calculated in the macula. Macular blood flow rates in AD group were significantly lower than MCI and CN groups (P 0.05). There were no significant differences of BFVs in arterioles and venules between AD and MCI (P > 0.05). (C) Vessel diameters were measured in the vessel segments crossing a circle (diameter 2.3 mm centered on the fovea) and there were no significant differences in both arterioles and venules among the three groups. Bars = standard error.
Fig 3. Representative thickness maps, sectoral thicknesses…
Fig 3. Representative thickness maps, sectoral thicknesses and two dimensional retinal images of ganglion cell-inner plexiform layer.
The retina was imaged using Zeiss Cirrus optical coherence tomography. AD: Alzheimer’s disease; MCI: Mild cognitive impairment; CN, cognitive normal.
Fig 4. The thickness of GCIPL.
Fig 4. The thickness of GCIPL.
(A) The thicknesses of GCIPL in the annulus of AD and MCI groups were significantly lower than the corresponding regions in CN group (P 0.05). Bars = standard error.
Fig 5. Relations between GCIPL thickness and…
Fig 5. Relations between GCIPL thickness and macular blood flow.
Annular GCIPL thickness and macular blood flow in both arterioles and venules were analyzed. There were no significant relations between GCIPL and blood flow rates in AD (A) and MCI (B). In contrast, GCIPL thickness was possibly related to blood flow rates in both arterioles and venules (C). Note both blood flow and GCIPL thickness spread out across the scales in AD and MCI groups, compared to CN group.

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