Min Soo Byun1, Sung Wook Park2,3,4,5, Jun Ho Lee6, Dahyun Yi7, So Yeon Jeon8, Hyo Jung Choi9, Haejung Joung9, Un Hyung Ghim2,3,4, Un Chul Park2,3,4, Yu Kyeong Kim10, Seong A Shin10, Hyeong Gon Yu2,3,4, Dong Young Lee7,9,11. 1. Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, Republic of Korea. 2. Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Republic of Korea. 3. Department of Ophthalmology, Seoul National University Hospital, Seoul, Republic of Korea. 4. Retinal Degeneration Laboratory, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea. 5. Seran Eye Center, Seoul, Republic of Korea. 6. Department of Neuropsychiatry, National Center for Mental Health, Seoul, Republic of Korea. 7. Institute of Human Behavioral Medicine, Medical Research Center Seoul National University, Seoul, Republic of Korea. 8. Department of Neuropsychiatry, Chungnam National University Hospital, Daejeon, Republic of Korea. 9. Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea. 10. Department of Nuclear Medicine, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea. 11. Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea.
Abstract
IMPORTANCE: Retinal biomarkers reflecting in vivo brain Alzheimer disease (AD) pathologic abnormalities could be a useful tool for screening cognitively normal (CN) individuals at the preclinical stage of AD. OBJECTIVES: To investigate the association of both functional and structural alterations of the retina with in vivo AD pathologic abnormalities in CN older adults and model a screening tool for detection of preclinical AD. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included a total of 49 CN individuals, and all assessment was done at the Seoul National University Hospital, Seoul, South Korea. All participants underwent complete ophthalmic examination, including swept-source optical coherence tomography (SS-OCT) and multifocal electroretinogram as well as amyloid-β (Aβ) positron emission tomography and magnetic resonance imaging. Data were collected from January 1, 2016, through October 31, 2017, and analyzed from February 1, 2018, through June 30, 2020. MAIN OUTCOMES AND MEASURES: For structural parameters of the retina, the thickness of the macula and layer-specific thicknesses, including peripapillary retinal nerve fiber layer and ganglion cell-inner plexiform layer measured by SS-OCT, were used for analysis. For functional parameters of the retina, implicit time and amplitude of rings 1 to 6 measured by multifocal electroretinogram were used. RESULTS: Of the 49 participants, 25 were women (51.0%); mean (SD) age was 70.6 (9.4) years. Compared with 33 CN individuals without Aβ deposition (Aβ-CN), the 16 participants with Aβ (Aβ+CN) showed reduced inner nasal macular thickness (mean [SD], 308.9 [18.4] vs 286.1 [22.5] μm; P = .007) and retinal nerve fiber layer thickness, particularly in the inferior quadrant (133.8 [17.9] vs 103.8 [43.5] μm; P = .003). In addition, the Aβ+CN group showed prolonged implicit time compared with the Aβ-CN group, particularly in ring 5 (41.3 [4.0] vs 38.2 [1.3] milliseconds; P = .002). AD-related neurodegeneration was correlated with the thickness of the ganglion cell-inner plexiform layer only (r = 0.41, P = .005). The model to differentiate the Aβ+CN vs Aβ-CN groups derived from the results showed 90% accuracy. CONCLUSIONS AND RELEVANCE: The findings of this study showing both functional as well as structural changes of retina measured by multifocal electroretinogram and SS-OCT in preclinical AD suggest the potential use of retinal biomarkers as a tool for early detection of in vivo AD pathologic abnormalities in CN older adults.
IMPORTANCE: Retinal biomarkers reflecting in vivo brain Alzheimer disease (AD) pathologic abnormalities could be a useful tool for screening cognitively normal (CN) individuals at the preclinical stage of AD. OBJECTIVES: To investigate the association of both functional and structural alterations of the retina with in vivo AD pathologic abnormalities in CN older adults and model a screening tool for detection of preclinical AD. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included a total of 49 CN individuals, and all assessment was done at the Seoul National University Hospital, Seoul, South Korea. All participants underwent complete ophthalmic examination, including swept-source optical coherence tomography (SS-OCT) and multifocal electroretinogram as well as amyloid-β (Aβ) positron emission tomography and magnetic resonance imaging. Data were collected from January 1, 2016, through October 31, 2017, and analyzed from February 1, 2018, through June 30, 2020. MAIN OUTCOMES AND MEASURES: For structural parameters of the retina, the thickness of the macula and layer-specific thicknesses, including peripapillary retinal nerve fiber layer and ganglion cell-inner plexiform layer measured by SS-OCT, were used for analysis. For functional parameters of the retina, implicit time and amplitude of rings 1 to 6 measured by multifocal electroretinogram were used. RESULTS: Of the 49 participants, 25 were women (51.0%); mean (SD) age was 70.6 (9.4) years. Compared with 33 CN individuals without Aβ deposition (Aβ-CN), the 16 participants with Aβ (Aβ+CN) showed reduced inner nasal macular thickness (mean [SD], 308.9 [18.4] vs 286.1 [22.5] μm; P = .007) and retinal nerve fiber layer thickness, particularly in the inferior quadrant (133.8 [17.9] vs 103.8 [43.5] μm; P = .003). In addition, the Aβ+CN group showed prolonged implicit time compared with the Aβ-CN group, particularly in ring 5 (41.3 [4.0] vs 38.2 [1.3] milliseconds; P = .002). AD-related neurodegeneration was correlated with the thickness of the ganglion cell-inner plexiform layer only (r = 0.41, P = .005). The model to differentiate the Aβ+CN vs Aβ-CN groups derived from the results showed 90% accuracy. CONCLUSIONS AND RELEVANCE: The findings of this study showing both functional as well as structural changes of retina measured by multifocal electroretinogram and SS-OCT in preclinical AD suggest the potential use of retinal biomarkers as a tool for early detection of in vivo AD pathologic abnormalities in CN older adults.
Authors: Steven M Silverstein; Joy J Choi; Kyle M Green; Kristen E Bowles-Johnson; Rajeev S Ramchandran Journal: Schizophr Bull Date: 2022-06-21 Impact factor: 7.348
Authors: Hyeong Min Kim; Ji Won Han; Young Joo Park; Jong Bin Bae; Se Joon Woo; Ki Woong Kim Journal: JAMA Ophthalmol Date: 2022-07-01 Impact factor: 8.253