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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 31  |  Issue : 2  |  Page : 126-130

Retinal changes in patients with mild cognitive impairment: An optical coherence tomography study


1 Department of Ophthalmology, Jubilee Mission Medical College, Thrissur, Kerala, India
2 Department of Psychiatry, Jubilee Mission Medical College, Thrissur, Kerala, India

Date of Web Publication27-Aug-2019

Correspondence Address:
Dr. Anju Kuriakose
Junior Resident, Department of Ophthalmology, Jubilee Mission Medical College, Thrissur, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/kjo.kjo_35_19

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  Abstract 


Background: Optical coherence tomography (OCT) is a noninvasive method of analyzing in vivo retinal architecture. It also measures retinal nerve fiber layer (RNFL) thickness, which is useful in managing diseases of the retina. Age-related thinning of the retinal ganglion cell complex has been measured using OCT. The present study is to evaluate the RNFL and ganglion cell layer (GCL) thickness using spectral domain OCT in patients with cognitive impairment (CI) and to study the correlation between RNFL and mini–mental state examination (MMSE) scores. Materials and Methods: A case–control study was done on 88 eyes of 44 patients, of which 27 belong to mild CI (MCI) and 17 were controls. They were assessed using MMSE/MINICOG/Montreal Cognitive Assessment tests and retinal OCT for RNFL, GCL, and inner plexiform layer (GCL + IPL) analysis. Results: RNFL thickness was reduced in all quadrants, more in superior and inferior quadrants in patients with MCI. GCL + IPL layer showed overall thinning in all quadrants, of which inferonasal and inferior quadrants were thinnest. Conclusion: MCI patients were prone to develop neurodegeneration even in the absence of microvascular changes in the retina. Hence, it is suggested to carry out routine evaluation of retina with OCT in all patients above the age of 60 to detect early neurodegenerative changes for early management. It is also noted that the sensitivity of GC + IPL was higher than that of RNFL to discriminate MCI from controls.

Keywords: Dementia, elderly, ganglion cell layer, mild cognitive impairment, optical coherence tomography, retinal nerve fiber layer


How to cite this article:
Kuriakose A, V. Kakkanatt AC, Mathai MT, Valsan N. Retinal changes in patients with mild cognitive impairment: An optical coherence tomography study. Kerala J Ophthalmol 2019;31:126-30

How to cite this URL:
Kuriakose A, V. Kakkanatt AC, Mathai MT, Valsan N. Retinal changes in patients with mild cognitive impairment: An optical coherence tomography study. Kerala J Ophthalmol [serial online] 2019 [cited 2019 Sep 20];31:126-30. Available from: http://www.kjophthal.com/text.asp?2019/31/2/126/265496




  Introduction Top


The estimated prevalence of dementia in the world is 46.8 million, which is expected to double by 2035.[1] Age comes with an increasing incidence of cognitive impairment (CI).[2] It is a clinical syndrome affecting about one-third of patients preceding dementia.[3] Early detection of CI can benefit population in various levels, which includes screening, early diagnosis, and immediate access to treatment.[4] About 10%–15% mild CI (MCI) patients will progress to Alzheimer's disease (AD) per year, while even 1%–2% of healthy controls are at risk of developing AD.[5]

The biological association between diseases of retina and brain is based on common development, as an extension from diencephalon.[6] There are structural similarities between retinal ganglion cell (RGC) and central nervous system (CNS) neurons.[7] The RGCs also undergo the same neurodegenerative processes affecting directly injured neurons, resulting in degeneration of axons, glial scar formation, and loss of myelin.

Optical coherence tomography (OCT) is a noninvasive technique which uses low-coherence interferometry to produce a two-dimensional image of optical scattering from internal tissue microstructures.[8] It affords clinicians the ability to quantify the thickness of the retinal nerve fiber layer (RNFL), which is useful in managing diseases of retina.

During aging, there is 1–3 μm thinning of the ganglion cell complex annually.[9] Both total retinal thickness and RNFL thickness significantly decrease with age.[10] Macular retinal pigment epithelium becomes more pleomorphic and opposite occurring in periphery.[11]


  Materials and Methods Top


This case–control study was done on 88 eyes of 44 patients, of whom 27 had MCI and 17 were controls. It was conducted in the Department of Ophthalmology and Psychiatry of a Tertiary Care Hospital in India during January 2017 to June 2018. After obtaining written consent, a detailed history and ophthalmic examination were done. Patients between the age group of 60–75 years with best-corrected visual acuity >6/12 and recently diagnosed patients with CI (less than a year) were included in the study.

Patients with ophthalmic conditions where OCT could not be done, neuropathies such as optic neuritis and glaucoma, congenital anomalies of optic disc, severe proven AD, and uncooperative/bedridden patients, were excluded from the study.

The assessment and grading of CI were based on the mini–mental state examination (MMSE) for literate patients and Montreal Cognitive Assessment (MOCA) scale/MINICOG test for illiterate patients.

Patients were assigned to Group 1 and Group 2 after complete neurological examination and MMSE.

  • Group 1 (cases: 27) – patients with MMSE score 10–23
  • Group 2 (control: 17) – patients with MMSE score >23.


OCT using Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA) without pupillary dilatation and under the same intensity of dim room lighting by the same specialist was done in both groups, and following parameters were evaluated.

  1. Peripapillary RNFL thickness measured as mean thickness in superior, inferior, nasal, and temporal quadrants
  2. Ganglion cell layer (GCL) with inner plexiform layer (IPL) thickness is measured in all six sectors: superonasal, inferonasal, superotemporal, inferotemporal, superior, and inferior sectors.


Changes in the above parameters were analyzed.

Statistical analysis was performed using independent two sample t-test for the parametric variables and Mann–Whitney U-test for nonparametric variables. To test the mean variables, Wilcoxon signed-rank test was used. To study the association of study variables with groups, Chi-square test was used.


  Results Top


Data were collected from 88 eyes of 44 patients of whom 27 belonged to Group 1 with MCI and 17 to Group 2 of controls. All the patients fulfilled the inclusion criteria:

Age distribution

This pie chart [Figure 1] shows distribution of the cases and controls. In Group 1 of MCI, the mean age was calculated to be 67 ± 3.79 years. In Group 2, the mean age was 64.29 ± 3.46 years. Youngest patient in the study was 60 years old, and oldest was 74 years.
Figure 1: Pie chart showing distribution of cases and controls

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Comparison of retinal nerve fiber layer in both groups

RNFL thickness is reduced in all the quadrants. Superior and inferior quadrants [Figure 2]a and [Figure 2]b show significant thinning in MCI patient (Group 1) compared to controls of Group 2 [Figure 3].
Figure 2: (a) Optical coherence tomography optic disc showing normal retinal nerve fiber layer thickness, (b) optical coherence tomography optic disc showing retinal nerve fiber layer thinning

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Figure 3: Bar chart showing comparison of Retinal Nerve Fiber Layer thickness in both groups. RT – Right, LT – Left, MT – Mean thickness, SUP – Superior, INF – Inferior

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Ganglion cell layer thickness

In this study, GCL + IPL layer showed overall thinning in all quadrants from the data obtained from both groups of which superotemporal, inferonasal, and inferior quadrants were the thinnest [Figure 4]a and [Figure 4]b. Inferonasal quadrant showed 68.82 ± 10.0, and inferior quadrant showed 69.00 ± 7.80 [Figure 5].
Figure 4: (a) Optical coherence tomography macula showing normal ganglion cell layer + inner plexiform layer thickness, (b) optical coherence tomography macula showing ganglion cell layer + inner plexiform layer thinning

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Figure 5: Bar chart showing comparison of Ganglion Cell Layer + Inner Plexiform Layer thickness in both groups. RT – Right, LT – Left, MT – mean thickness, SUP – Superior, INF – Inferior, SN – Superonasal, IN – Inferonasal, ST – Superotemporal, IT – Inferotemporal

Click here to view



  Discussion Top


Our study was to evaluate the RNFL and GCL thickness using spectral domain OCT in patients with MCI. We also studied the correlation between RNFL and MMSE scores and found that RNFL showed significant thinning in MCI patients compared to age-matched controls. RNFL OCT showed significant thinning in superior and inferior quadrants. GCL + IPL layer showed significant thinning specifically in superotemporal and inferonasal quadrants.

To understand the connection between the retina and brain, various intense studies have been carried out by researchers worldwide. London et al. in their study explained the biological association between diseases of retina and brain. During the development of embryo, both the retina and optic nerve are extensions from diencephalon of CNS.[6] Thus, the microvasculature system shares common physiology, while the blood-ocular barrier closely resembles the structure and properties of the blood–brain barrier.[7] Hence, there are structural similarities between the RGC and CNS neurons, as well as the optic nerve fiber tract with other fiber tracts of the CNS. The RGCs also undergo the same neurodegenerative processes affecting directly injured neurons, resulting in degeneration of axons, glial scar formation, and loss of myelin.[6],[7]

The prevalence of dementia in people aged over 60 is fairly uniform across the world – between 5% and 7% as per Lee et al. Our study also showed the mean age in Group 1 (MCI) as 67 ± 3.79 years and Group 2 (control) as 64.29 ± 3.46 years.

The correlation between retinal structural degeneration (OCT parameters) and the CI (MMSE scores) in MCI was analyzed, and our findings confirmed a significant correlation between MMSE scores and several OCT parameters. This finding is in accordance with a study by Cunha et al. on the quantification of neural loss with CI.[12] Iseri et al. also found a significant correlation between total macular volume and MMSE score in AD and MCI patients.[13]

Comparison of retinal nerve fiber layer thickness with other studies

The study conducted by Liu et al. found a significant decrease in RNFL thickness in superior and inferior quadrants of AD compared to MCI.[5] Our study also showed significant thinning in superior quadrant (P < 0.05) [Table 1].
Table 1: Comparison of retinal nerve fiber layer with other studies

Click here to view


Kesler et al. and Shen et al. in their study concluded significant decrease in RNFL in the inferior quadrants of patients with AD and MCI compared with controls.[15] In addition, inferior quadrant RNFL thickness was inversely associated with better cognitive function.[19] Our study also showed significant thinning in the inferior quadrant.

In a cross-sectional study conducted by Invernizzi et al., they compared retinal layer thickness of HIV-infected patients with CI and HIV-infected patients without CI. Totally, 69 cases and 70 controls were included and assessed using MOCA. GCL thickness correlated positively with cognitive function and negatively with age in HIV patients.[20] Our study also used MOCA to assess the CI and to study the thinning in the RNFL.

Cheung et al. in their study suggested that the sensitivity of GC-IPL was generally higher than that of RNFL to discriminate AD and MCI from the controls.[17] Similarly, Shao et al. studied that the thickness differences were negative (thinning) mainly RNFL and macular ganglion cell and inner plexiform layer in both AD and MCI groups in comparison to controls.[21] Our study was also in accordance with the above studies showed similar finding with significant thinning in all quadrants, and superonasal and superotemporal showed statistically significant thinning (P < 0.05).

Lad et al. and Choi et al. in their study suggested that macular GCL + IPL thickness can serve as noninvasive promising biomarkers to diagnose and monitor the progression of MCI to AD. He also suggested that NFL and GCIPL may undergo dynamic changes during AD progression.[22],[23]


  Conclusion Top


The mean RNFL and mean GCL + IPL layer showed thinning in MCI patients. RNFL-OCT showed significant thinning in superior and inferior quadrants. GCL + IPL layer showed significant thinning specifically in superior and inferior quadrant. Significant correlation of age with retinal thinning was noted.

It can be concluded that MCI patients were found to develop neurodegeneration of retina (measurable on OCT) in the absence of detectable microvascular changes. Hence, it is suggested to make it a routine evaluation of retina with the help of OCT in all patients above the age of 60 years, to detect early neurodegenerative changes for early diagnosis and management. This study suggests that the sensitivity of GC-IPL was generally higher than that of RNFL to discriminate MCI from the controls.

Acknowledgments

The authors would like to acknowledge the support from Jubilee Mission Medical College, Thrissur.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Lee MJ, Abraham AG, Swenor BK, Sharrett AR, Ramulu PY. Application of optical coherence tomography in the detection and classification of cognitive decline. J Curr Glaucoma Pract 2018;12:10-8.  Back to cited text no. 1
    
2.
Luck T, Luppa M, Briel S, Riedel-Heller SG. Incidence of mild cognitive impairment: A systematic review. Dement Geriatr Cogn Disord 2010;29:164-75.  Back to cited text no. 2
    
3.
Mitchell AJ, Shiri-Feshki M. Rate of progression of mild cognitive impairment to dementia – Meta-analysis of 41 robust inception cohort studies. Acta Psychiatr Scand 2009;119:252-65.  Back to cited text no. 3
    
4.
Etgen T, Sander D, Bickel H, Förstl H. Mild cognitive impairment and dementia: The importance of modifiable risk factors. Dtsch Arztebl Int 2011;108:743-50.  Back to cited text no. 4
    
5.
Liu D, Zhang L, Li Z, Zhang X, Wu Y, Yang H, et al. Thinner changes of the retinal nerve fiber layer in patients with mild cognitive impairment and Alzheimer's disease. BMC Neurol 2015;15:14.  Back to cited text no. 5
    
6.
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.  Back to cited text no. 6
    
7.
Ikram MK, Cheung CY, Wong TY, Chen CP. Retinal pathology as biomarker for cognitive impairment and Alzheimer's disease. J Neurol Neurosurg Psychiatry 2012;83:917-22.  Back to cited text no. 7
    
8.
Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W, et al. Optical coherence tomography. Science 1991;254:1178-81.  Back to cited text no. 8
    
9.
Shariati MA, Park JH, Liao YJ. Optical coherence tomography study of retinal changes in normal aging and after ischemia. Invest Ophthalmol Vis Sci 2015;56:2790-7.  Back to cited text no. 9
    
10.
Alamouti B, Funk J. Retinal thickness decreases with age: An OCT study. Br J Ophthalmol 2003;87:899-901.  Back to cited text no. 10
    
11.
Friedman E, Ts'o MO. The retinal pigment epithelium. II. Histologic changes associated with age. Arch Ophthalmol 1968;79:315-20.  Back to cited text no. 11
    
12.
Cunha LP, Lopes LC, Costa-Cunha LV, Costa CF, Pires LA, Almeida AL, et al. Macular thickness measurements with frequency domain-OCT for quantification of retinal neural loss and its correlation with cognitive impairment in Alzheimer's disease. PLoS One 2016;11:e0153830.  Back to cited text no. 12
    
13.
Iseri PK, Altinaş O, Tokay T, Yüksel N. Relationship between cognitive impairment and retinal morphological and visual functional abnormalities in Alzheimer disease. J Neuroophthalmol 2006;26:18-24.  Back to cited text no. 13
    
14.
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;420:97-9.  Back to cited text no. 14
    
15.
Kesler A, Vakhapova V, Korczyn AD, Naftaliev E, Neudorfer M. Retinal thickness in patients with mild cognitive impairment and Alzheimer's disease. Clin Neurol Neurosurg 2011;113:523-6.  Back to cited text no. 15
    
16.
Ascaso FJ, Cruz N, Modrego PJ, Lopez-Anton R, Santabárbara J, Pascual LF, et al. Retinal alterations in mild cognitive impairment and Alzheimer's disease: An optical coherence tomography study. J Neurol 2014;261:1522-30.  Back to cited text no. 16
    
17.
Cheung CY, Ong YT, Hilal S, Ikram MK, Low S, Ong YL, et al. Retinal ganglion cell analysis using high-definition optical coherence tomography in patients with mild cognitive impairment and Alzheimer's disease. J Alzheimers Dis 2015;45:45-56.  Back to cited text no. 17
    
18.
Gao L, Liu Y, Li X, Bai Q, Liu P. Abnormal retinal nerve fiber layer thickness and macula lutea in patients with mild cognitive impairment and Alzheimer's disease. Arch Gerontol Geriatr 2015;60:162-7.  Back to cited text no. 18
    
19.
Shen Y, Liu L, Cheng Y, Feng W, Shi Z, Zhu Y, et al. Retinal nerve fiber layer thickness is associated with episodic memory deficit in mild cognitive impairment patients. Curr Alzheimer Res 2014;11:259-66.  Back to cited text no. 19
    
20.
Invernizzi A, Acquistapace A, Bochicchio S, Resnati C, Rusconi S, Ferrari M, et al. Correlation between inner retinal layer thickness and cognitive function in HIV: New insights from an exploratory study. AIDS 2018;32:1485-90.  Back to cited text no. 20
    
21.
Shao Y, Jiang H, Wei Y, Shi Y, Shi C, Wright CB, et al. Visualization of focal thinning of the ganglion cell-inner plexiform layer in patients with mild cognitive impairment and Alzheimer's disease. J Alzheimers Dis 2018;64:1261-73.  Back to cited text no. 21
    
22.
Lad EM, Mukherjee D, Stinnett SS, Cousins SW, Potter GG, Burke JR, et al. Evaluation of inner retinal layers as biomarkers in mild cognitive impairment to moderate Alzheimer's disease. PLoS One 2018;13:e0192646.  Back to cited text no. 22
    
23.
Choi SH, Park SJ, Kim NR. Macular ganglion cell -inner plexiform layer thickness is associated with clinical progression in mild cognitive impairment and Alzheimer's disease. PLoS One 2016;11:e0162202.  Back to cited text no. 23
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1]



 

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