Retinal Nerve Fiber Layer Thickness and Cerebrospinal Fluid Aβ/Tau

Association of Retinal Nerve Fiber Layer (RNFL) Thickness With Cerebrospinal Fluid Aβ and Tau Concentration

To test the hypothesis that retinal nerve fiber layer (RNFL) thickness is correlated with Aβ and Tau concentration of cerebrospinal fluid (CSF) in an older population.

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Procedure: surgery

Detailed Description

retinal nerve fiber layer (RNFL) thickness changing has been reported in Alzheimer's Disease (AD) patients at an early stage, and has been demonstrated as a potential biomarker able to predict cognitive deterioration (Hinton DR et al., N Engl J Med 1986; London A et al. Nat Rev Neurol 2013; Chang LY et al., Alzheimers Dement 2014). However, whether RNFL thickness is correlated with cerebrospinal fluid (CSF) features of AD pathogenesis (e.g., Aβ and Tau) remains unclear. The investigators thus conducted this observational cohort study to test the correlation between RNFL thickness changing and CSF, to further validate RNFL as a potential AD biomarker.

• Study Type: Observational
• Enrollment (Actual): 86

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200072
      • Shanghai 10th People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

A total of 300 old adults who were scheduled to have elective total hip or knee replacement surgery, ureteroscopic lithotripsy and transurethral resection of the prostate at the Shanghai 10th People's Hospital were asked to participate in this study. A total of 104 participants were enrolled from August 2013 to December 2014, and the data from 86 participants were finally included in the study.

Description

Inclusion Criteria:

1. 50 years old or older;
2. five years or more of education and scores of MMSE ≥ 24 points;
3. Chinese as their first language;
4. Having spinal anesthesia.

Exclusion Criteria:

1. prior diagnoses of neurologic diseases, e.g., dementia, Parkinson's diseases, multiple sclerosis or stroke according to DSM-IV;
2. history of mental disorders (e.g., major depressive disorder and schizophrenia) diagnosed according to DSM-IV;
3. known diseases contributing to the retina pathologies, e.g., diabetes, glaucoma or increased intraocular pressure (more than 22 mmHg), cataract, and macular degeneration and hypermyopia;
4. unwillingness to comply with the cognitive assessments;
5. ungradable images of OCT.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
elderly participants with surgery; The studied cohort were participants 50 years old or older, without a diagnosis of dementia, and scheduled to have orthopedic or urological surgery under spinal anesthesia at Shanghai 10th People's Hospital.	Procedure: surgery; All participants were scheduled to have elective total hip or knee replacement surgery, ureteroscopic lithotripsy and transurethral resection of the prostate under spinal anesthesia at the Shanghai 10th People's Hospital. After 5 years, the investigaors will follow up the participants including cognitive functions, PET-CT, thickness of Retinal Nerve Fiber Layer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Specific cognitive function	Neuropsychological test battery to assess specific cognitive function, including immediate memory, visuospatial memory and executive function.	Within one week before surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
retinal nerve fiber layer (RNFL) thickness	Optical coherence tomography (Carl Zeiss Meditec, Inc., Dublin, CA, USA) to measure RNFL thickness	Within one week before surgery
Cerebrospinal fluid (CSF) Aβ concentration	ELISA kits (Aβ40: Cat. # 292-62301; Aβ42: Cat. # 296-64401, Wako, Richmond, VA) to measure Aβ concentration	During the spinal anesthesia before the administration of the local anesthetic.
Cerebrospinal fluid (CSF) Tau concentration	ELISA kits (Tau: Cat. # KHB0041, Invitrogen, San Francisco, CA) to measure Aβ concentration	During the spinal anesthesia before the administration of the local anesthetic.
Global cognitive state	Mini-Mental State Examination (MMSE) to assess global cognitive function	Within one week before surgery

Collaborators and Investigators

• Sponsor: Shanghai 10th People's Hospital
• Collaborators: Massachusetts General Hospital
• Investigators: Principal Investigator: Yuan Shen, MD, PhD, Shanghai 10th People's Hospital

Publications and helpful links

General Publications

• London A, Benhar I, Schwartz M. The retina as a window to the brain-from eye research to CNS disorders. Nat Rev Neurol. 2013 Jan;9(1):44-53. doi: 10.1038/nrneurol.2012.227. Epub 2012 Nov 20.
• Chang LY, Lowe J, Ardiles A, Lim J, Grey AC, Robertson K, Danesh-Meyer H, Palacios AG, Acosta ML. Alzheimer's disease in the human eye. Clinical tests that identify ocular and visual information processing deficit as biomarkers. Alzheimers Dement. 2014 Mar;10(2):251-61. doi: 10.1016/j.jalz.2013.06.004. Epub 2013 Sep 5.
• Hinton DR, Sadun AA, Blanks JC, Miller CA. Optic-nerve degeneration in Alzheimer's disease. N Engl J Med. 1986 Aug 21;315(8):485-7. doi: 10.1056/NEJM198608213150804.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2013
• Primary Completion (Actual): December 31, 2014
• Study Completion (Actual): December 31, 2014

Study Registration Dates

• First Submitted: February 17, 2018
• First Submitted That Met QC Criteria: February 21, 2018
• First Posted (Actual): February 27, 2018

Study Record Updates

• Last Update Posted (Actual): November 30, 2018
• Last Update Submitted That Met QC Criteria: November 28, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: retinal nerve fiber layer; cerebrospinal fluid Aβ and Tau
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: dsyy001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No