Retinal Tissue Hypoperfusion in Patients with Clinical Alzheimer's Disease

Overview

Journal Eye Vis (Lond)

Publisher Biomed Central

Specialty Ophthalmology

Date 2018 Aug 25

PMID 30140712

Citations 12

Authors

Giovana Rosa Gameiro

Hong Jiang

Yi Liu

Yuqing Deng

Xiaoyan Sun

Bernardo Nascentes

Bernard Baumel

Tatjana Rundek

Jianhua Wang

Affiliations

Soon will be listed here.

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/mm (mean ± standard deviation) and was significantly lower than in CN subjects (3.62 ± 0.44 nl/s/mm, < 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 mm in CAD patients and 6% lower than CN subjects (0.50 ± 0.05 mm, < 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.

Citing Articles

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References

Landa G, Jangi A, Garcia P, Rosen R . Initial report of quantification of retinal blood flow velocity in normal human subjects using the Retinal Functional Imager (RFI). Int Ophthalmol. 2012; 32(3):211-5. DOI: 10.1007/s10792-012-9547-z. View

Landa G, Rosen R . New patterns of retinal collateral circulation are exposed by a retinal functional imager (RFI). Br J Ophthalmol. 2009; 94(1):54-8. DOI: 10.1136/bjo.2009.161257. View

Tan J, Yang Y, Jiang H, Liu C, Deng Z, Lam B . The measurement repeatability using different partition methods of intraretinal tomographic thickness maps in healthy human subjects. Clin Ophthalmol. 2016; 10:2403-2415. PMC: 5136365. DOI: 10.2147/OPTH.S117494. View

Burgansky-Eliash Z, Lowenstein A, Neuderfer M, Kesler A, Barash H, Nelson D . The correlation between retinal blood flow velocity measured by the retinal function imager and various physiological parameters. Ophthalmic Surg Lasers Imaging Retina. 2013; 44(1):51-8. DOI: 10.3928/23258160-20121221-13. View

Kur J, Newman E, Chan-Ling T . Cellular and physiological mechanisms underlying blood flow regulation in the retina and choroid in health and disease. Prog Retin Eye Res. 2012; 31(5):377-406. PMC: 3418965. DOI: 10.1016/j.preteyeres.2012.04.004. View

de la Torre J . Cerebral hemodynamics and vascular risk factors: setting the stage for Alzheimer's disease. J Alzheimers Dis. 2012; 32(3):553-67. DOI: 10.3233/JAD-2012-120793. View

Campbell J, Zhang M, Hwang T, Bailey S, Wilson D, Jia Y . Detailed Vascular Anatomy of the Human Retina by Projection-Resolved Optical Coherence Tomography Angiography. Sci Rep. 2017; 7:42201. PMC: 5301488. DOI: 10.1038/srep42201. View

Jiang H, Liu Y, Wei Y, Shi Y, Wright C, Sun X . Impaired retinal microcirculation in patients with Alzheimer's disease. PLoS One. 2018; 13(2):e0192154. PMC: 5796702. DOI: 10.1371/journal.pone.0192154. View

Hays C, Zlatar Z, Wierenga C . The Utility of Cerebral Blood Flow as a Biomarker of Preclinical Alzheimer's Disease. Cell Mol Neurobiol. 2016; 36(2):167-79. PMC: 5278904. DOI: 10.1007/s10571-015-0261-z. View

10.

Chen J, Rosas H, Salat D . Age-associated reductions in cerebral blood flow are independent from regional atrophy. Neuroimage. 2010; 55(2):468-78. PMC: 3435846. DOI: 10.1016/j.neuroimage.2010.12.032. View

11.

den Haan J, Janssen S, van de Kreeke J, Scheltens P, Verbraak F, Bouwman F . Retinal thickness correlates with parietal cortical atrophy in early-onset Alzheimer's disease and controls. Alzheimers Dement (Amst). 2017; 10:49-55. PMC: 5699891. DOI: 10.1016/j.dadm.2017.10.005. View

12.

Lopes de Faria J, Duarte D, Larico Chavez R, Arthur A, Arthur R, Iano Y . Reliability and validity of digital assessment of perifoveal capillary network measurement using high-resolution imaging. Br J Ophthalmol. 2014; 98(6):726-9. DOI: 10.1136/bjophthalmol-2013-304100. View

13.

Morrison J, Hof P . Life and death of neurons in the aging brain. Science. 1997; 278(5337):412-9. DOI: 10.1126/science.278.5337.412. View

14.

Landa G, Garcia P, Rosen R . Correlation between retina blood flow velocity assessed by retinal function imager and retina thickness estimated by scanning laser ophthalmoscopy/optical coherence tomography. Ophthalmologica. 2009; 223(3):155-61. DOI: 10.1159/000189819. View

15.

Jiang H, Delgado S, Tan J, Liu C, Rammohan K, DeBuc D . Impaired retinal microcirculation in multiple sclerosis. Mult Scler. 2016; 22(14):1812-1820. PMC: 4993688. DOI: 10.1177/1352458516631035. View

16.

McKhann G, Knopman D, Chertkow H, Hyman B, Jack Jr C, Kawas C . The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011; 7(3):263-9. PMC: 3312024. DOI: 10.1016/j.jalz.2011.03.005. View

17.

Austin B, Nair V, Meier T, Xu G, Rowley H, Carlsson C . Effects of hypoperfusion in Alzheimer's disease. J Alzheimers Dis. 2011; 26 Suppl 3:123-33. PMC: 3303148. DOI: 10.3233/JAD-2011-0010. View

18.

Jiang H, Wei Y, Shi Y, Wright C, Sun X, Gregori G . Altered Macular Microvasculature in Mild Cognitive Impairment and Alzheimer Disease. J Neuroophthalmol. 2017; 38(3):292-298. PMC: 5902666. DOI: 10.1097/WNO.0000000000000580. View

19.

Choi S, Park S, Kim N . Macular Ganglion Cell -Inner Plexiform Layer Thickness Is Associated with Clinical Progression in Mild Cognitive Impairment and Alzheimers Disease. PLoS One. 2016; 11(9):e0162202. PMC: 5012569. DOI: 10.1371/journal.pone.0162202. View

20.

Poels M, Ikram M, Vernooij M, Krestin G, Hofman A, Niessen W . Total cerebral blood flow in relation to cognitive function: the Rotterdam Scan Study. J Cereb Blood Flow Metab. 2008; 28(10):1652-5. DOI: 10.1038/jcbfm.2008.62. View