Corneal nerve fiber loss relates to cognitive impairment in patients with Parkinson\u2019s disease

Ning-Ning Che,Rayaz A Malik,Jian-Jun Ma,Hong-Qi Yang,Qiu-Huan Jiang,Guan-Xiao Ding,Zhen-Xiang Zhao,Xue Li,Si-Yuan Chen

doi:10.1038/s41531-021-00225-3

Abstract

Cognitive impairment in Parkinson’s disease (PD) adversely influences quality of life. There is currently no available biomarker to predict cognitive decline in PD. Corneal confocal microscopy (CCM) has been used as a non-invasive tool for quantifying small nerve damage in PD. The present study investigated whether corneal nerve measures were associated with cognitive function in PD. Patients with PD were classified into those with normal cognitive function (PD-CN), mild cognitive impairment (PD-MCI), and dementia (PDD). Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), and corneal nerve fiber length (CNFL) were quantified with CCM and compared with a control group. Sixty-five PD patients and thirty controls were studied. CNFD was decreased and CNBD was increased in PD patients compared to controls (P < 0.05). CNBD and CNBD/CNFD ratio was higher in PD-CN compared to controls. CNFD was positively correlated with the Montreal cognitive assessment (MoCA) score (r = 0.683, P < 0.001), but negatively associated with unified Parkinson disease rating scale (UPDRS)-part III (r = −0.481, P < 0.001) and total UPDRS scores (r = −0.401, P = 0.001) in PD patients. There was no correlation between CNFD and Levodopa equivalent daily dose (LEDD) (r = 0.176, P = 0.161). CNFD, CNBD, CNFL, and CNBD/CNFD ratio was lower with increasing Hoehn and Yahr stage. PD patients show evidence of corneal nerve loss compared with controls and corneal nerve parameters are associated with the severity of cognitive and motor dysfunction in PD. CCM could serve as an objective in vivo ophthalmic imaging technique to assess neurodegeneration in PD.

Highlights

Parkinson’s disease (PD) is the second most common neurodegenerative disorder affecting the elderly worldwide[1]. the primary focus is on motor symptoms in PD, cognitive impairment, hyposmia, and autonomic dysfunction, referred to as non-motor symptoms (NMS), are increasingly recognized[2]
Two kinds of peripheral neuropathy have been proposed in PD according to the peripheral nerves involved[18,19]
It usually develops in advanced PD patients[19] and can be diagnosed with nerve conduction studies

Summary

Introduction

Parkinson’s disease (PD) is the second most common neurodegenerative disorder affecting the elderly worldwide[1]. the primary focus is on motor symptoms in PD, cognitive impairment, hyposmia, and autonomic dysfunction, referred to as non-motor symptoms (NMS), are increasingly recognized[2]. With the advance of disease course, patients will experience deteriorated motor function, they will suffer much more from NMS, like cognitive impairment, hallucinations, psychosis symptoms, and eventually dementia etc. Over 40% of patients with normal cognition developed MCI within 6 years of being diagnosed with PD3 and 80% develop dementia[4]. Cognitive decline in PD encompasses the full spectrum of cognitive impairment include early mild subjective cognitive decline (SCD), mild cognitive impairment (PD-MCI), and Parkinson’s disease dementia (PDD)[6]. In PD-MCI, insidious cognitive decline may be noticed by the patient, relative or clinician, but it does not interfere significantly with daily life[6,7]. While in PDD, cognitive decline can severely impair daily life and functional independence[8]. PD is traditionally regarded as a central neurodegenerative disorder, but peripheral nerve degeneration has been observed[9,10,11]

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