Comparison of OCTA Factors in Patients With or Without Amyloid Pathology: A Prospective Study

NCT05475158 | Completed

• 1 other identifier: 1908-004-081
• Study Type: observational
• Target: 117
• Locations: 1 country
• Sites: 1

Brief Summary

To compare alternation of retinal microcirculation within the macula and optic disc in patients with dementia, mild cognitive impairment (MCI), and cognitively healthy subjects who had positive amyloid biomarkers (Aβ +) or not, using optical coherence tomography angiography (OCTA).

Conditions

Alzheimer Disease; Amyloid Angiopathy; Macular Ischemia; Dementia; Mild Cognitive Impairment

Keywords

Alzheimer disease dementia; Mild cognitive impairment; Amyloid pathology; Optical coherence tomographic angiography

Outcome Measures

Primary Outcomes (2)

• SD-OCT imaging

  Measuring macular GC/IPLT (μm) and cimcumpapillary RNFLT (μm). The average, minimum, and 6 sectoral (superotemporal, superior, superonasal, inferonasal, inferior, and inferotemporal) GC/IPLT (μm) values are obtained. The average, 4 sectoral (temporal, superior, nasal, and inferior), and 12 clock-hour circumpapillary RNFLT (μm) are obtained. Multiple measurements will not be aggregated, but analyzed respectively.

  Through study completion, measured at enrollment and analyzed from September 2019 to July 2021

• SD-OCTA imaging

  Acquiring microvasculature images of macular (6 × 6 mm\^2 scan) and optic disc areas (4.5 × 4.5 mm\^2 scan). The average vessel density (VD, mm/mm\^2) and perfusion density (PD, %) were automatically measured in the Early Treatment of Diabetic Retinopathy Study (ETDRS) grid with values shown in the nine subfields, central, inner, outer and full region. The software calculated the area (mm\^2), perimeter (mm), and circularity (defined as 4πA/P\^2, where A was the area and P was the perimeter) of foveal avascular zone (FAZ). A circularity closer to 0 means an irregular shape, and closure to 1 indicates a circular shape. Multiple measurements will not be aggregated, but analyzed respectively.

  Through study completion, measured at enrollment and analyzed from September 2019 to July 2021

Secondary Outcomes (2)

• Diagnostic performance

  Through study completion, analyzed from July 2021 to July 2022

• Correlations

  Through study completion, analyzed from July 2021 to July 2022

Study Arms (5)

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).

MCI (Mild cognitive impairment)

Patients with mild cognitive impairment (MCI) met the Petersen's criteria.

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.

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).

Aβ negative

Aβ negative was within normal limits.

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Neurologic Clinic of Pusan National University Hospital

You may qualify if:

• Clinical and pathologic diagnosis of ADD or MCI as well as cognitively unimpaired control (CU) from the Neurologic Clinic of Pusan National University Hospital

You may not qualify if:

• Patient not within the ages of 50-90 years old
• 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

Sponsors & Collaborators

• Pusan National University Hospital: lead

Study Sites (1)

Pusan National University Hospital

Busan, 49241, South Korea

Location

Related Publications (24)

• 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.

  PMID: 31638686 BACKGROUND

• 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.

  PMID: 23477989 BACKGROUND

• 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. Erratum In: Lancet Neurol. 2012 Aug;11(8):658.

  PMID: 22749065 BACKGROUND

• 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.

  PMID: 21514249 BACKGROUND

• 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.

  PMID: 21124753 BACKGROUND

• 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.

  PMID: 20182034 BACKGROUND

• 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.

  PMID: 17071920 BACKGROUND

• 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.

  PMID: 1996878 BACKGROUND

• 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.

  PMID: 2819446 BACKGROUND

• 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.

  PMID: 2314849 BACKGROUND

• 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.

  PMID: 29394263 BACKGROUND

• 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.

  PMID: 20946471 BACKGROUND

• 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.

  PMID: 27239502 BACKGROUND

• 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.

  PMID: 17460292 BACKGROUND

• 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.

  PMID: 32153141 BACKGROUND

• 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.

  PMID: 27023249 BACKGROUND

• 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.

  PMID: 30073360 BACKGROUND

• 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.

  PMID: 25795476 BACKGROUND

• 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.

  PMID: 28600299 BACKGROUND

• 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.

  PMID: 29040211 BACKGROUND

• 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.

  PMID: 30352114 BACKGROUND

• 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.

  PMID: 30939178 BACKGROUND

• 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.

  PMID: 31193094 BACKGROUND

• 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.

  PMID: 31118186 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease; Amyloid angiopathy; Dementia; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Study Officials

• Eun-Joo Kim, MD, PhD

  Department of Neurology, Pusan National University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2022
• First Posted: July 26, 2022
• Study Start: September 1, 2019
• Primary Completion: July 31, 2021
• Study Completion: July 31, 2021
• Last Updated: July 26, 2022

Record last verified: 2022-07

Locations

KR (1)