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Cognitive impairment and markers of optical neurodegeneration in early multiple sclerosis



Cognitive impairment and retinal atrophy have been proposed as two potential markers of neurodegeneration in multiple sclerosis (MS). We aimed at assessing the relation between peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell layer (mGCL) atrophy and cognitive performance in early MS.


This is a multicenter cross-sectional study on patients with early MS (clinically isolated syndrome and relapsing–remitting MS), with an EDSS score ≤ 3.0. Patients with previous optic neuritis, other ocular diseases, psychiatric illness, or recent relapse were excluded. All patients underwent standardized optical coherence tomography (OCT) and neuropsychological evaluation with validated tests for MS patients. Cognitive impairment was defined as having two cognitive tasks below age- and education-adjusted norms.


We recruited 52 patients with early MS, with an average age of 37 years (SD = 10.5), an average disease duration of 3.69 years (SD = 2.3), and a median EDSS of 1.0 (IQR = 0.5). In this sample, 15/52 patients presented cognitive impairment. Regarding OCT measurements, 7/52 patients had an average pRNFL below the 5th percentile and 2/52 had an average mGCL below the 5th percentile. The average pRNFL thickness was comparable in cognitively impaired and cognitively preserved patients (100.3 μm vs 103.1 μm, p = 0.52); the average mGCL thickness had also similar values between groups (50.5 μm vs 53 μm, p = 0.38).


Cognitive impairment was frequent in our sample of early MS. However, no association with reduced pRNFL or mGCL thickness was found. When compared to OCT, cognitive assessment could provide an earlier marker of neurodegeneration in MS.

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The authors gratefully acknowledge the support of Biogen Idec.

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Correspondence to Luís Ruano.

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All the enrolled patients provided informed consent and the study was approved by the ethical committees of all recruiting institutions. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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The authors declare no competing interests.

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All the enrolled patients provided informed consent.

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Silva, R., Coelho, P., Seabra, M. et al. Cognitive impairment and markers of optical neurodegeneration in early multiple sclerosis. Neurol Sci 43, 4381–4386 (2022).

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  • Multiple sclerosis
  • Cognitive impairment
  • Optical coherence tomography
  • Neurodegeneration