title: Meta-analysis of the relationship of peripheral retinal nerve fiber layer thickness to Alzheimer's disease and mild cognitive impairment.
abstract: BACKGROUND
  Previous studies report that the thickness of the peripheral retinal nerve fiber layer (RNFL) in individuals with Alzheimer's disease (AD) and mild cognitive impairment (MCI) is significantly thinner than in normal controls (NC), but RNFL thickness in different quadrants of the optic nerve remains unclear.
  
  
  OBJECTIVE
  Conduct a systematic review of studies that assess peripheral RNFL thickness in AD and MCI.
  
  
  METHODS
  Based on pre-defined criteria, studies in English or Chinese were identified from PubMed, Embase, ISI web of knowledge, Ovid/Medline, Science Direct, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Chongqing VIP database, WANFANG DATA, and the China BioMedical Literature Service System (SinoMed). Review Manager 5.3 was used for analysis.
  
  
  RESULTS
  The 19 cross-sectional studies identified had a pooled sample of 1455 individuals. There was substantial heterogeneity between studies that compared RNFL in AD or MCI to normal controls, but this heterogeneity was primarily restricted to low-quality studies. Combining 6 high-quality studies (n=578) indicated that total RNFL thickness and the thickness of superior and inferior RNFL quadrants in AD were significantly thinner than in normal controls. Similarly, combining 5 high-quality studies (n=541) indicated significantly thinner total RNFL thickness in MCI than in controls. Six studies (n=589) found thinner RNFL in the superior and inferior quadrants in MCI than in controls;and 6 studies (n=487) found thinner RNFL in the temporal quadrant in MCI than in controls. Finally, 7 studies (n=432) indicated that total RNFL was thinner in AD than in MCI, and 6 studies (n=364) indicated thinner RNFL in the superior and inferior quadrants in AD than in MCI.
  
  
  CONCLUSIONS
  Much of the heterogeneity in results from previous studies may be due to poor methodology. Peripheral RNFL thicknesses, particularly in the superior and inferior quadrants, becomes progressively thinner as cognitive function declines, so this could be a candidate biomarker for early identification of AD. Methodologically rigorous studies in large population-based cohort studies that follow elderly individuals over time and that simultaneously collect information on potential mediating factors (such as blood pressure, blood glucose, and lipid levels) are needed to confirm or disprove the potential predictive value of RNFL.
authors.affiliation: Department of Psychiatry, Tenth People's Hospital of Tong Ji University, Shanghai, China.
authors.forename: Meijuan
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, Tenth People's Hospital of Tong Ji University, Shanghai, China.
authors.forename: Yinbo
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Psychiatry, Tenth People's Hospital of Tong Ji University, Shanghai, China.
authors.forename: Zhongyong
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Chunbo
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Psychiatry, Tenth People's Hospital of Tong Ji University, Shanghai, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Shen
keywords: Alzheimer’s disease; meta-analysis; mild cognitive impairment; retinal nerve fiber layer