The relationship between cognitive impairment and changes in retinal neuroarchitectonics

Close metadata

OBJECTIVE

To study the relationship between cognitive deficits and retinal neuroarchitectonics in Alzheimer’s disease, vascular dementia, and glaucoma based on optical coherence tomography.

MATERIAL AND METHODS

A comprehensive examination of 90 patients with Alzheimer’s disease, vascular dementia and glaucoma was conducted. The patients were divided into three groups of 30 people each. The groups were comparable by gender and age and initial socio-economic status. All patients underwent a comprehensive neurological and neuropsychological study as well as optical coherence tomography.

RESULTS AND CONCLUSION

The results of optical coherence tomography in Alzheimer’s disease and glaucoma reveal retinal changes in the perifocal region in the upper and lower quadrants. In patients with vascular dementia, the process is observed in the foveal (central) region of the retina, which can be considered as a potential biomarker of the neurodegenerative damage. The severity of cognitive deficit in the Alzheimer’s disease group correlates with the degree of degeneration in the layers of the peripapillary layer of the nerve fibers of the retina of the temporal region, the perifocal region of the lower quadrant of the retina, ganglion cells, and the inner plexiform layers of the retina. In the vascular dementia group, the severity of cognitive deficit positively correlates with the degree of cell degeneration in the foveal region of the inner plexiform retinal layer.

Keywords:

Alzheimer’s disease

vascular dementia

glaucoma

optical coherence tomography

biomarker

retina

retinal perifoveal region

foveal region of the retina

Authors:

Bogolepova A.N.

Pirogov Russian National Research Medical University;
Federal Center of Brain Research and Neurotechnologies of the Federal Medical Biological Agency

SPIN RSCI: 6775-0279
Scopus AuthorID: 6602240836
ORCID: 0000-0002-6327-3546

Makhnovich E.V.

Pirogov Russian National Research Medical University;
Federal Center of Brain Research and Neurotechnologies

ORCID: 0000-0002-8606-5715

Zhuravleva A.N.

Helmholtz National Medical Research Center of Eye Diseases

ORCID: 0000-0001-8381-2124

Received:

29.06.2020

Accepted:

03.07.2020

List of references:

Trofimov EO, Izvecov NV. Analysis of the market of drugs for the treatment of dementia in Russia. Remedium. 2019;9:16-25. (In Russ.). https://doi.org/10.21518/1561-5936-2019-9-16-25
Gusev EI, Bogolepova AN. Cognitive disorders in cerebrovascular diseases. M.: Medpress-inform; 2013. (In Russ.).
Bogolepova AN, Zhuravleva AN, Makhnovich EV. Prospects for diagnosing Alzheimer’s disease using optical coherence tomography. Zhurnal Nevrologii i Psihiatrii im. S.S. Korsakova. 2017;117(9):112-117. (In Russ.). https://doi.org/10.17116/jnevro201711791112-117
Prince M, Albanese E, Guerchet M, Prina M. World Alzheimer Report 2014: Dementia and risk reduction an analysis of protective and modifiable factors. 2014;5(15):61-104. https://www.alz.co.uk/research/WorldAlzheimerReport2014.pdf
World Alzheimer Report 2015. The Global Impact of Dementia An analysis of prevalence, incidence, cost and trends. Published by Alzheimer`s Disease International (ADI). London. 2015. https://www.dementiaallianceinternational.org/wp-content/uploads/2015/08/World-Alzheimer-Report-2015-Summary-2015.
Dementia. Who fact sheet. December 2018. (In Russ.). https://www.who.int/mediacentre/factsheets/fs362/ru
Querfurth HW, LaFerla FM. Alzheimer’s disease. N Engl J Med. 2010;362(4):329-444. https://doi.org/10.1056/NEJMra0909142
Kivipelto M, Helkala EL, Laakso MP, Hänninen T, Hallikainen M, Alhainen K, Soininen H, Tuomilehto J, Nissinen A. Midlife vascular risk factors and Alzheimer’s disease in later life: Longitudinal, population basedstudy. BMJ. 2001;3:22:1447-1451. https://doi.org/10.1136/bmj.322.7300.1447
Luchsinger JA, Gustafson DR. Adiposity, type 2 diabetes, and Alzheimer’s disease. J Alzheimers Dis. 2009;16:693-704. https://doi.org/10.3233/JAD-2009-1022
Colligris P, Perez de Lara MJ, Colligris B, Pintor J. Ocular manifestations of Alzheimer’s and other neurodegenerative diseases: The prospect of the eye as a tool for the early diagnosis of Alzheimer’s disease. J Ophthalmol. 2018;8538573:1-12. https://doi.org/10.1155/2018/8538573
Bogolepova AN, Makhnovich EV, Zhuravleva AN. Visual disorders and Alzheimer’s disease. Pharmateca. 2017; 2(4):13325-13373. (In Russ.).
Braak H, Braak E. Evolution of neuropathology of Aizheimer’s and progression of AD as reflected by Braak stage 30, 37, 38 In disease. Acta Neurol Scand Suppl. 1996;165:3-12. https://doi.org/10.1111/j.1600-0404.1996.tb05866.x
Bogolepova AN. Sleep disorders and Alzheimer’s disease. Neurology, Neuropsychiatry, Psychosomatics. 2018;10(1):74-77. (In Russ.). https://doi.org/10.14412/2074-2711-2018-1-74-77
Javaid FZ, Brenton J, Guo L, Cordeiro MF. Visual and ocular manifestations of AD and their use as biomarkers for diagnosis and progression. Front Neurol. 2016;7:55. https://doi.org/10.3389/fneur.2016.00055
Sadun AA. Axon caliber populations in the human optic nerve: change with age and disease. Int Neuro-Oph Society. 1986;7(5):5-20.
Katz B, Rimmer S. Ophthalmologic manifestations of Alzheimer’s disease. Surv Ophthalmol. 1989;34:31-43. https://doi.org/10.1016/j.archger.2009.09.035
Salamone G, Di lorenzo C, Mosti S, Lupo F, Cravello L, Palmer K, Musicco M, Caltagirone C. Color discrimination performance in patients with Alzheimer’s disease. Dement Geriatr Cogn Disord. 2009; 27(6):501-7.
Tzekov R, Mullan M. Vision function abnormalities in Alzheimer disease. Surv Ophthalmol. 2014;59:414-433. https://doi.org/10.1016/j.survophthal.2013.10.002
Liu D, Zhang L, Li Z, Zhang X, Wu Y, Yang H, Min B, Zhang X, Ma D, Lu Y. Thinner changes of the retinal nerve fiber layer in patients with mild cognitive impairment and Alzheimer’s disease. BMC Neurol. 2015;15(1):14.
Gehring WJ. The master control gene for morphogenesis and evolution of the eye. Genes Cells. 1996;1:11-5. https://doi.org/10.1046/j.1365-2443.1996.11011.x
Tuoc TC, Radyushkin K, Tonchev AB, Piñon MC, Ashery-Padan R, Molnár Z, Davidoff MS, Stoykova A. Selective cortical layering abnormalities and behavioral deficits in cortex-specific PAX6 knock-out mice. J Neurosci. 2009;29:8335-8349. https://doi.org/10.1523/JNEUROSCI.5669-08.2009
Heins N, Malatesta P, Cecconi F, Nakafuku M, Tucker KL, Hack MA, Hack MA, Chapouton P, Barde YA, Gotz M Glial cells generate neurons: The role of the transcription factor Pax6. Nat Neurosci. 2002;5:308-315. https://doi.org/10.1038/nn0502-500c
Hinton DR, Sadun AA, Blanks JC, Miller CA. Optic-nerve degeneration in Alzheimer’s disease. N Engl J Med. 1986;315:485-487.
La Morgia C, Ross-Cisneros FN, Koronyo Y, Hannibal J, Gallassi R, Cantalupo G, Sambati L, Pan BX, Tozer KR, Barboni P, Provini F, Avanzini P, Carbonelli M, Pelosi A, Chui H, Liguori R, Baruzzi A, Koronyo-Hamaoui M, Sadun AA, Carelli V. Melanopsin retinal ganglion cell loss in Alzheimer disease. Ann Neurol. 2016;79:90-109. https://doi.org/10.1002/ana.24548
Hart NJ, Koronyo Y, Black KL, Koronyo-Hamaoui M. Ocular indicators of Alzheimer’s: exploring disease in the retina. Acta Neuropathol. 2016;132:767-787. https://doi.org/10.1007/s00401-016-1613-6
Alexandrov PN, Pogue A, Bhattacharjee S, Lukiw WJ. Retinal amyloid peptides and complement factor H in transgenic models of Alzheimer’s disease. Neuroreport. 2011;22:623-627. https://doi.org/10.1097/WNR.0b013e3283497334
Koronyo-Hamaoui M, Koronyo Y, Ljubimov AV, Ca M, Ko MK, Black KL, Schwartz M, Farkas DL. Identiﬁcation of amyloid plaques in retinas from Alzheimer’s patients and noninvasive in vivo optical imaging of retinal plaques in a mouse model. Neuroimage. 2011;54(suppl 1):204-217. https://doi.org/10.1016/j.neuroimage.2010.06.020
Liu B, Rasool S, Yang Z, Glabe CG, Schreiber SS, Ge J, Tan Z. Amyloid-peptide vaccinations reduce β-amyloid plaques but exacerbate vascular deposition and inflammation in the retina of Alzheimer’s transgenic mice. Am J Pathol. 2009;175(5):2099-2110. https://doi.org/10.2353/ajpath.2009.090159
He XF, Liu YT, Peng C, Zhang F, Zhuang S, Zhang JS. Optical coherence tomography assessed retinal nerve fiber layer thickness in patients with Alzheimer’s disease: a meta-analysis. Int J Ophthalmol. 2012;5(3):1-5.
Bambo MP, Garcia-Martin E, Gutierrez-Ruiz F, Pinilla J, Perez-Olivan S, Larrosa J M, Polo V, Pablo L. Analysis of optic disk color changes in Alzheimer’s disease: a potential new biomarker. Clin Neurol Neurosurg. 2015;132:68-73. https://doi.org/10.1212/01.wnl.0000244490.07925.8b
Bogolepova AN, Zhuravleva AN, Makhnovich EV. Prospects for diagnosing Alzheimer’s disease using optical coherence tomography. Journal of Neurology and Psychiatry. 2017;117(9):112-117. (In Russ.). https://doi.org/10.17116/jnevro201711791112-117
Chan VT, Sun Z, Tang S, Chen LJ, Wong A, Tham CC, Lad EM. Spectral-domain OCT measurements in Alzheimer’s disease: a systematic review and meta-analysis. Ophthalmology. 2019;126(4):497-510. https://doi.org/10.1016/j.ophtha.2018.08.009
Thomson KL, Cameron JR, Pal S. A systematic review and meta-analysis of retinal nerve fiber layer change in dementia, using optical coherence tomography. Alzheimer’s Dement. Diagnosis, Assess. Dis Monit. 2015;1(2):136-143.
Fujino Y, Delucia MW, Davies P, Dickson DW. Ballooned neurones in the limbic lobe are associated with Alzheimer type pathology and lack diagnostic specificity. Neuropathology and Applied Neurobiology. 2004;30(6):676-682.
Reichenbach A, Wurm A, Pannicke T, Iandiev I, Wiedemann P, Bringmann A. Müller cells as players in retinal degeneration and edema. Graefe’s Archive for Clinical and Experimental Ophthalmology. 2007;245(5):627-636. https://doi.org/10.1007/s00417-006-0516-y
Knoll B, Simonett J, Volpe NJ, Farsiu S, Ward M, Rademaker A, Weintraub S, Fawzi AA. Retinal nerve fiber layer thickness in amnestic mild cognitive impairment: Case-control study and meta-analysis. Alzheimer’s Dement. 2016;4(2):85-93. https://doi.org/10.1016/j.dadm.2016.07.004
Erichev VP, Panyushkina LA, Fomin AV. Optical coherence tomography of the retina and optic nerve in the diagnosis of Alzheimer’s disease. Glaucoma. Journal of the research Institute GB RAMN. 2013;1:5-10. (In Russ.).
Ascaso FJ, Cruz N, Modrego PJ, Lopez-Anton R, Santabárbara J, Pascual LF, Lobo A, Cristóbal JA. Retinal alterations in mild cognitive impairment and Alzheimer’s disease: an optical coherence tomography study. J Neurol. 2014;261(8):1522-1530. https://doi.org/10.1007/s00415-014-7374-z
Turski GN, Schmitz-Valckenberg S, Holz FG, Finger RP. Retinal imaging of the macula and optic disc in neurodegenerative diseases. Der Ophthalmol. Zeitschrift der Dtsch. Ophthalmol Gesellschaft. 2017;14(2):114-119. https://doi.org/10.1007/s00347-016-0412-8
World Health Organization. Dementia:A Public Health Priority. Geneva: World Health Organization; 2012. Accessed March 21, 2018. https://apps.who.int/iris/bitsream/10665/75263/1/9789241564458_eng.pdf
Paul RH. Vascular dementia: cerebrovascular mechanisms and clinical management. Springer Science. 2005;45(2):456-459. ID: 71837201.
Kiseleva OA, Robustova OV, Bessmertny AM, Zakharova EK, Avdeev RV. Prevalence of primary glaucoma in representatives of different races and ethnic groups in Russia and CIS countries. Ophthalmology. 2014;10(4):11-15. (In Russ.).
Gusev EI, Grechko VE, Burd GS. Nervous diseases. M.: Medicine; 1988. (In Russ.).
Folstein MF, Folstein SE, McHugh PR. «Mini-mental state»: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189-198. https://doi.org/10.1016/0022-3956(75)90026-6
Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005;53(4):695-699. https://doi.org/10.1111/j.1532-5415.2005.53221.x
Dubois B, Slachevsky A, Litvan I, Pillon B. The FAB: a frontal assessment battery at bedside. Neurology. 2000;55(11):1621-1626. https://doi.org/10.1212/WNL.55.11.1621
Gharbiya M, Trebbastoni A, Parisi F, Manganiello S, Cruciani F, D’Antonio F, De Vico U, Imbriano L, Campanelli A, De Lena C. Choroidal thinning as a new finding in Alzheimer’s Disease: Evidence from enhanced depth imaging spectral domain optical coherence tomography. J Alzheimer’s Dis. 2014;40(4):907-917. https://doi.org/10.3233/JAD-132039
Berisha F, Feke G T, Trempe C L, McMeel J W, Schepens C L. Retinal abnormalities in early Alzheimer’s disease. Invest. Ophthalmol Vis Sci. 2007;48(5):2285-2289. https://doi.org/10.1167/iovs.06-1029
Choi SH, Park SJ, Kim NR. Macular ganglion cell-inner plexiform layer thickness is associated with clinical progression in mild cognitive impairment and Alzheimers disease. Othtalm. 2016;11(9):16-22. https://doi.org/10.1371/journal.pone.0162202
Paquet C, Boissonnot M, Roger F, Dighiero P, Gil R, Hugon J. Abnormal retinal thickness in patients with mild cognitive impairment and Alzheimer’s disease. Neurosci Lett. 2007;420(2):97-99. https://doi.org/10.1016/j.neulet.2007.02.090

Close metadata