Optical coherence tomography angiography in preclinical Alzheimer's disease

Jacoba Alida van de Kreeke, Hoang-Ton Nguyen, Elles Konijnenberg, Jori Tomassen, Anouk den Braber, Mara Ten Kate, Maqsood Yaqub, Bart van Berckel, Adriaan A Lammertsma, Dorret I Boomsma, Stevie H Tan, Frank Verbraak, Pieter Jelle Visser, Jacoba Alida van de Kreeke, Hoang-Ton Nguyen, Elles Konijnenberg, Jori Tomassen, Anouk den Braber, Mara Ten Kate, Maqsood Yaqub, Bart van Berckel, Adriaan A Lammertsma, Dorret I Boomsma, Stevie H Tan, Frank Verbraak, Pieter Jelle Visser

Abstract

Background/aims: As a protrusion from the brain, the retina might reflect the status of the brain. Previous studies showed a decrease in vessel density and foveal avascular zone (FAZ) enlargement on optical coherence tomography angiography (OCTA) in individuals suffering from Alzheimer's disease (AD). This study aims to assess whether such changes are already present in preclinical stages of AD, in a population of monozygotic (MZ) twins.

Methods: 124 cognitively healthy individuals (MZ twins, ages 60-93 years) underwent [18F]flutemetamol amyloid positron emission tomography (PET) scanning and OCTA. PET scans were visually rated for cortical amyloid-beta (Aβ) positivity. Parametric global cortical non-displaceable binding potential (BPND) was used as a continuous measure for Aβ aggregation. FAZ size and vessel densities for the inner and outer ring of the macular ETDRS grid and in a 3-6 mm ring around the optic nerve head (ONH) were measured.OCTA measures were associated with visual Aβ score, BPND and amyloid load estimated by twin concordance on visual Aβ score. Twin correlations were estimated as a measure of maximum heritability of OCTA measures.

Results: 13 of 124 participants were Aβ+. Aβ+ individuals had significantly higher vessel density than Aβ- individuals in all regions but did not differ in FAZ size. Twin analyses showed a positive association between and vessel densities in all regions. BPND tended to be associated with higher vessel density in the inner ring. Twin correlations were moderate/high for all OCTA parameters except vessel density around the ONH, which correlated weakly.

Conclusion: Retinal vessel density was higher in individuals with preclinical AD.

Keywords: diagnostic tests/investigation; imaging; retina.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

References

    1. Lewis F. Estimation of future cases of dementia from those born in 2015. Consulting report July 2015. Office of Health Economics, 2015.
    1. Eratne D, Loi SM, Farrand S, et al. . Alzheimer's disease paper 1: clinical update on epidemiology, pathophysiology and diagnosis. Australas Psychiatry 2018;1039856218762308.
    1. Sun BL, WW L, Zhu C, et al. . Clinical research on Alzheimer's disease: progress and perspectives. Neurosci Bull 2018.
    1. Viña J, Sanz-Ros J. Alzheimer's disease: only prevention makes sense. Eur J Clin Invest 2018;48:e13005 10.1111/eci.13005
    1. Jansen WJ, Ossenkoppele R, Knol DL, et al. . Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis. JAMA 2015;313:1924–38. 10.1001/jama.2015.4668
    1. Jack CR, Barrio JR, Kepe V. Cerebral amyloid PET imaging in Alzheimer's disease. Acta Neuropathol 2013;126:643–57. 10.1007/s00401-013-1185-7
    1. Vlassenko AG, Benzinger TLS, Morris JC. PET amyloid-beta imaging in preclinical Alzheimer's disease. Biochim Biophys Acta 2012;1822:370–9. 10.1016/j.bbadis.2011.11.005
    1. Hornberger J, Bae J, Watson I, et al. . Clinical and cost implications of amyloid beta detection with amyloid beta positron emission tomography imaging in early Alzheimer's disease - the case of florbetapir. Curr Med Res Opin 2017;33:675–85. 10.1080/03007995.2016.1277197
    1. Nishii R, Higashi T, Kagawa S, et al. . 18F-FPYBF-2, a new F- labelled amyloid imaging PET tracer: biodistribution and radiation dosimetry assessment of first-in-man 18F-FPYBF-2 PET imaging. Ann Nucl Med 2018;32:256–63. 10.1007/s12149-018-1240-5
    1. London A, Benhar I, Schwartz M. The retina as a window to the brain-from eye research to CNS disorders. Nat Rev Neurol 2013;9:44–53. 10.1038/nrneurol.2012.227
    1. den Haan J, Verbraak FD, Visser PJ, et al. . Retinal thickness in Alzheimer's disease: a systematic review and meta-analysis. Alzheimers Dement 2017;6:162–70.
    1. Frost S, Martins RN, Kanagasingam Y. Ocular biomarkers for early detection of Alzheimer's disease. JAD 2010;22:1–16. 10.3233/JAD-2010-100819
    1. McGrory S, Cameron JR, Pellegrini E, et al. . The application of retinal fundus camera imaging in dementia: a systematic review. Alzheimers Dement 2017;6:91–107. 10.1016/j.dadm.2016.11.001
    1. Huang D, Swanson EA, Lin CP, et al. . Optical coherence tomography. Science 1991;254:1178–81. 10.1126/science.1957169
    1. Jellinger KA. Alzheimer disease and cerebrovascular pathology: an update. J Neural Transm 2002;109:813–36. 10.1007/s007020200068
    1. Bulut M, Kurtuluş F, Gözkaya O, et al. . Evaluation of optical coherence tomography angiographic findings in Alzheimer's type dementia. Br J Ophthalmol 2018;102:233–7. 10.1136/bjophthalmol-2017-310476
    1. Jiang H, Wei Y, Shi Y, et al. . Altered macular microvasculature in mild cognitive impairment and Alzheimer disease. J Neuroophthalmol 2018;38:292–8. 10.1097/WNO.0000000000000580
    1. Grewal DS, Polascik BW, Hoffmeyer GC, et al. . Assessment of differences in retinal microvasculature using OCT angiography in Alzheimer's disease: a twin discordance report. Ophthalmic Surg Lasers Imaging Retina 2018;49:440–4. 10.3928/23258160-20180601-09
    1. Boomsma DI, de Geus EJC, Vink JM, et al. . Netherlands twin register: from twins to twin families. Twin Res Hum Genet 2006;9:849–57. 10.1375/twin.9.6.849
    1. Konijnenberg E, Carter SF, ten Kate M, et al. . The EMIF-AD PreclinAD study: study design and baseline cohort overview. Alz Res Therapy 2018;10 10.1186/s13195-018-0406-7
    1. Heeman FY M, Heurling K, Alves L. P20: Optimized coffee-break protocol for quantitative [18F]flutemetamol studies. Human Amyloid Imaging Conference, Miami, Florida, 2018.
    1. Gunn RN, Lammertsma AA, Hume SP, et al. . Parametric imaging of ligand-receptor binding in PET using a simplified reference region model. Neuroimage 1997;6:279–87. 10.1006/nimg.1997.0303
    1. Wu Y, Carson RE. Noise reduction in the simplified reference tissue model for neuroreceptor functional imaging. J Cereb Blood Flow Metab 2002;22:1440–52. 10.1097/01.WCB.0000033967.83623.34
    1. Boellaard R, Yaqub M, Lubberink M, et al. . PPET: a software tool for kinetic and parametric analyses of dynamic PET studies. Neuroimage 2006;31 10.1016/j.neuroimage.2006.04.053
    1. Hammers A, Allom R, Koepp MJ, et al. . Three-dimensional maximum probability atlas of the human brain, with particular reference to the temporal lobe. Hum Brain Mapp 2003;19:224–47. 10.1002/hbm.10123
    1. Tolboom N, Yaqub M, van der Flier WM, et al. . Detection of Alzheimer pathology in vivo using both 11C-PIB and 18F-FDDNP PET. J Nucl Med 2009;50:191–7. 10.2967/jnumed.108.056499
    1. Collij L, Konijnenberg E, Reimand J, et al. . Assessing Amyloid Pathology in Cognitively Normal Subjects using [(18)F]Flutemetamol PET: Comparing Visual Reads and Quantitative Methods. J Nucl Med 2018.
    1. Holm S. A simple sequentially rejective multiple test procedure. Scandinavian Journal of Statistics 1979;6:65–70.
    1. Vitaro F, Brendgen M, Arseneault L. The discordant MZ-twin method: one step closer to the Holy Grail of causality. Int J Behav Dev 2009;33:376–82. 10.1177/0165025409340805
    1. Kinney JW, Bemiller SM, Murtishaw AS, et al. . Inflammation as a central mechanism in Alzheimer's disease. Alzheimers Dement 2018;4:575–90.
    1. Sousa DC, Leal I, Moreira S, et al. . Hypoxia challenge test and retinal circulation changes - a study using ocular coherence tomography angiography. Acta Ophthalmol 2018;96:e315–9. 10.1111/aos.13622
    1. Marchesi VT. Alzheimer's dementia begins as a disease of small blood vessels, damaged by oxidative-induced inflammation and dysregulated amyloid metabolism: implications for early detection and therapy. Faseb J 2011;25:5–13. 10.1096/fj.11-0102ufm
    1. O'Bryhim BE, Apte RS, Kung N, et al. . Association of preclinical Alzheimer disease with optical coherence tomographic angiography findings. JAMA Ophthalmol 2018;136:1242–8. 10.1001/jamaophthalmol.2018.3556
    1. van de Kreeke JA, Nguyen HT, Konijnenberg E, et al. . Retinal and cerebral microvasculopathy: relationships and their genetic contributions. Invest Ophthalmol Vis Sci 2018;59:5025–31. 10.1167/iovs.18-25341
    1. De Moor MHM, Boomsma DI, Stubbe JH, et al. . Testing causality in the association between regular exercise and symptoms of anxiety and depression. Arch Gen Psychiatry 2008;65:897–905. 10.1001/archpsyc.65.8.897
    1. Donohue MC, Sperling RA, Petersen R, et al. . Association between elevated brain amyloid and subsequent cognitive decline among cognitively normal persons. JAMA 2017;317:2305–16. 10.1001/jama.2017.6669

Source: PubMed

3
購読する