Comparison of OCTA Factors in Patients With or Without Amyloid Pathology: A Prospective Study
NCT ID: NCT05475158
Last Updated: 2022-07-26
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
117 participants
OBSERVATIONAL
2019-09-01
2021-07-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
OCT Angiography and NRAI in Dementia
NCT03761381
Optical Coherence Tomography in Cerebral Amyloidosis
NCT03472482
Relationship Between Alzheimer Disease and Diminution of the Three Macular Nervous Retinal Layers
NCT04794634
OCT-Angiography and Adaptive Optics in Patients With Memory Impairment
NCT04389437
OCTA (Optical Coherence Angiography Tomography) Versus Structural OCT(Optical Coherence Tomography) in Neovascular AMD (Age Macular Degeneration)
NCT03939195
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Patients with ADD commonly show visuospatial dysfunction which is mainly attributed to damage of parieto-occipital or temporo-occipital visual pathway. In addition, previous studies using optical coherence tomography (OCT) which is a useful tool measuring retinal nerve fiber layer thickness (RNFLT), macula ganglion cell/inner plexiform layer thickness (GC/IPLT) reported impaired pregeniculate afferent visual pathway, for example, reduction of RNFLT and loss of retinal ganglionic cells (RGCs) in patients with ADD.
The retina and brain have the same embryological origin. These were branched off from the forebrain, so the brain and retina have similar anatomic and physiologic traits of the vasculature. In line with this, several studies using laser doppler ultrasonography, or retinal function imager (RFI) revealed narrowed central retinal vein and decreased its blood velocity, or low blood flow rate of retinal arterioles and venules in patients with mild cognitive impairment (MCI) and ADD. The authors suggested that in patients with ADD, accumulation of Aβ in the vessel walls could cause disruption of basement membrane and endothelium, leading to the decreased vascular lumen and density of retinal vessel. Indeed, postmortem study revealed accumulated Aβ inside or around RGCs in AD.
OCTA can clearly visualize not only the specific layers of retinal vasculatures, including superficial, middle, and deep capillary plexuses, but also choroidal vessels with a high resolution and in a reproducible manner, without contrast agent. A few prior studies using OCTA reported enlarged foveal avascular zone (FAZ) and decrease of retinal vascular density and choroidal thickness in ADD or MCI compared to controls. On the other hand, the others showed no differences in FAZ area and vessel density between them.
In this study, the investigators first evaluated structural and microvascular changes of retina and the microvascular change of macula and optic disc in patients with clinically diagnosed ADD, MCI and cognitively normal controls using OCT and OCTA. Then, to investigate whether impaired pregeniculate visual pathway is truly associated with underlying amyloid pathology, the investigators further investigated those OCT and OCTA parameters in each subgroup with positive or negative amyloid biomarker.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
COHORT
PROSPECTIVE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Dementia
Patients with Alzheimer disease dementia (ADD) fulfilled the NIA-AA core clinical criteria for probable ADD and Aβ positive according to ATN classification scheme.
Aβ positive refers to Aβ pathology (CSF Aβ1-42 \< 631.8 pg/ml or positive amyloid deposits on 18F-flutemetamol PET by visual inspection).
No interventions assigned to this group
MCI (Mild cognitive impairment)
Patients with mild cognitive impairment (MCI) met the Petersen's criteria.
No interventions assigned to this group
CU (Cognitively unimpaired control)
CU consisted of cognitively unimpaired subjects whose cognition (as defined by the Seoul Neuropsychological Screening Battery (SNSB)) was within normal limits.
No interventions assigned to this group
Aβ positive
Aβ positive refers to Aβ pathology (CSF Aβ1-42 \< 631.8 pg/ml or positive amyloid deposits on 18F-flutemetamol PET by visual inspection).
No interventions assigned to this group
Aβ negative
Aβ negative was within normal limits.
No interventions assigned to this group
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
Exclusion Criteria
* Patient with glaucoma, macular degeneration, retinal vascular disease including diabetic retinopathy, retinal vein occlusion
* Intraocular pressure (IOP) ≥ 21 mmHg
* Dense corneal or ocular media opacity
* History of ocular trauma or associated ocular disease
* Astigmatism ≥ 3.0 diopter or spherical equivalent ≥ 6.0 diopter
* Best corrected visual acuity (BCVA) \< 20/40
* Any ocular surgery except uncomplicated cataract extraction
* Uncontrolled hypertension and diabetes
50 Years
90 Years
ALL
Yes
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Pusan National University Hospital
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Eun-Joo Kim, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Department of Neurology, Pusan National University Hospital
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Pusan National University Hospital
Busan, , South Korea
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Arvanitakis Z, Shah RC, Bennett DA. Diagnosis and Management of Dementia: Review. JAMA. 2019 Oct 22;322(16):1589-1599. doi: 10.1001/jama.2019.4782.
Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O, Szoeke C, Macaulay SL, Martins R, Maruff P, Ames D, Rowe CC, Masters CL; Australian Imaging Biomarkers and Lifestyle (AIBL) Research Group. Amyloid beta deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: a prospective cohort study. Lancet Neurol. 2013 Apr;12(4):357-67. doi: 10.1016/S1474-4422(13)70044-9. Epub 2013 Mar 8.
Clark CM, Pontecorvo MJ, Beach TG, Bedell BJ, Coleman RE, Doraiswamy PM, Fleisher AS, Reiman EM, Sabbagh MN, Sadowsky CH, Schneider JA, Arora A, Carpenter AP, Flitter ML, Joshi AD, Krautkramer MJ, Lu M, Mintun MA, Skovronsky DM; AV-45-A16 Study Group. Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-beta plaques: a prospective cohort study. Lancet Neurol. 2012 Aug;11(8):669-78. doi: 10.1016/S1474-4422(12)70142-4. Epub 2012 Jun 28.
Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, Snyder PJ, Carrillo MC, Thies B, Phelps CH. The diagnosis of mild cognitive impairment 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 May;7(3):270-9. doi: 10.1016/j.jalz.2011.03.008. Epub 2011 Apr 21.
Grossman I, Lutz MW, Crenshaw DG, Saunders AM, Burns DK, Roses AD. Alzheimer's disease: diagnostics, prognostics and the road to prevention. EPMA J. 2010 Jun;1(2):293-303. doi: 10.1007/s13167-010-0024-3. Epub 2010 Jun 29.
Kirby E, Bandelow S, Hogervorst E. Visual impairment in Alzheimer's disease: a critical review. J Alzheimers Dis. 2010;21(1):15-34. doi: 10.3233/JAD-2010-080785.
Hodges JR. Alzheimer's centennial legacy: origins, landmarks and the current status of knowledge concerning cognitive aspects. Brain. 2006 Nov;129(Pt 11):2811-22. doi: 10.1093/brain/awl275.
Cronin-Golomb A, Corkin S, Rizzo JF, Cohen J, Growdon JH, Banks KS. Visual dysfunction in Alzheimer's disease: relation to normal aging. Ann Neurol. 1991 Jan;29(1):41-52. doi: 10.1002/ana.410290110.
Blanks JC, Hinton DR, Sadun AA, Miller CA. Retinal ganglion cell degeneration in Alzheimer's disease. Brain Res. 1989 Nov 6;501(2):364-72. doi: 10.1016/0006-8993(89)90653-7.
Sadun AA, Bassi CJ. Optic nerve damage in Alzheimer's disease. Ophthalmology. 1990 Jan;97(1):9-17. doi: 10.1016/s0161-6420(90)32621-0.
Jiang H, Liu Y, Wei Y, Shi Y, Wright CB, Sun X, Rundek T, Baumel BS, Landman J, Wang J. Impaired retinal microcirculation in patients with Alzheimer's disease. PLoS One. 2018 Feb 2;13(2):e0192154. doi: 10.1371/journal.pone.0192154. eCollection 2018.
Brown WR, Thore CR. Review: cerebral microvascular pathology in ageing and neurodegeneration. Neuropathol Appl Neurobiol. 2011 Feb;37(1):56-74. doi: 10.1111/j.1365-2990.2010.01139.x.
Feke GT, Hyman BT, Stern RA, Pasquale LR. Retinal blood flow in mild cognitive impairment and Alzheimer's disease. Alzheimers Dement (Amst). 2015 Apr 23;1(2):144-51. doi: 10.1016/j.dadm.2015.01.004. eCollection 2015 Jun.
Berisha F, Feke GT, Trempe CL, McMeel JW, Schepens CL. Retinal abnormalities in early Alzheimer's disease. Invest Ophthalmol Vis Sci. 2007 May;48(5):2285-9. doi: 10.1167/iovs.06-1029.
Wu J, Zhang X, Azhati G, Li T, Xu G, Liu F. Retinal microvascular attenuation in mental cognitive impairment and Alzheimer's disease by optical coherence tomography angiography. Acta Ophthalmol. 2020 Sep;98(6):e781-e787. doi: 10.1111/aos.14381. Epub 2020 Mar 9.
Rosenfeld PJ, Durbin MK, Roisman L, Zheng F, Miller A, Robbins G, Schaal KB, Gregori G. ZEISS Angioplex Spectral Domain Optical Coherence Tomography Angiography: Technical Aspects. Dev Ophthalmol. 2016;56:18-29. doi: 10.1159/000442773. Epub 2016 Mar 15.
Nesper PL, Fawzi AA. Human Parafoveal Capillary Vascular Anatomy and Connectivity Revealed by Optical Coherence Tomography Angiography. Invest Ophthalmol Vis Sci. 2018 Aug 1;59(10):3858-3867. doi: 10.1167/iovs.18-24710.
de Carlo TE, Bonini Filho MA, Chin AT, Adhi M, Ferrara D, Baumal CR, Witkin AJ, Reichel E, Duker JS, Waheed NK. Spectral-domain optical coherence tomography angiography of choroidal neovascularization. Ophthalmology. 2015 Jun;122(6):1228-38. doi: 10.1016/j.ophtha.2015.01.029. Epub 2015 Mar 17.
Bulut M, Kurtulus F, Gozkaya O, Erol MK, Cengiz A, Akidan M, Yaman A. Evaluation of optical coherence tomography angiographic findings in Alzheimer's type dementia. Br J Ophthalmol. 2018 Feb;102(2):233-237. doi: 10.1136/bjophthalmol-2017-310476. Epub 2017 Jun 9.
Jiang H, Wei Y, Shi Y, Wright CB, Sun X, Gregori G, Zheng F, Vanner EA, Lam BL, Rundek T, Wang J. Altered Macular Microvasculature in Mild Cognitive Impairment and Alzheimer Disease. J Neuroophthalmol. 2018 Sep;38(3):292-298. doi: 10.1097/WNO.0000000000000580.
O'Bryhim BE, Apte RS, Kung N, Coble D, Van Stavern GP. Association of Preclinical Alzheimer Disease With Optical Coherence Tomographic Angiography Findings. JAMA Ophthalmol. 2018 Nov 1;136(11):1242-1248. doi: 10.1001/jamaophthalmol.2018.3556.
Zhang YS, Zhou N, Knoll BM, Samra S, Ward MR, Weintraub S, Fawzi AA. Parafoveal vessel loss and correlation between peripapillary vessel density and cognitive performance in amnestic mild cognitive impairment and early Alzheimer's Disease on optical coherence tomography angiography. PLoS One. 2019 Apr 2;14(4):e0214685. doi: 10.1371/journal.pone.0214685. eCollection 2019.
den Haan J, van de Kreeke JA, van Berckel BN, Barkhof F, Teunissen CE, Scheltens P, Verbraak FD, Bouwman FH. Is retinal vasculature a biomarker in amyloid proven Alzheimer's disease? Alzheimers Dement (Amst). 2019 May 10;11:383-391. doi: 10.1016/j.dadm.2019.03.006. eCollection 2019 Dec.
van de Kreeke JA, Nguyen HT, Konijnenberg E, Tomassen J, den Braber A, Ten Kate M, Yaqub M, van Berckel B, Lammertsma AA, Boomsma DI, Tan SH, Verbraak F, Visser PJ. Optical coherence tomography angiography in preclinical Alzheimer's disease. Br J Ophthalmol. 2020 Feb;104(2):157-161. doi: 10.1136/bjophthalmol-2019-314127. Epub 2019 May 22.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
1908-004-081
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.