Associations of inner retinal layers with risk of incident dementia: An individual participant data analysis of four prospective cohort studies

Alzheimers Dement. 2024 Jan;20(1):211-220. doi: 10.1002/alz.13167. Epub 2023 Aug 8.


Introduction: Our main objective was to investigate whether retinal neurodegeneration, estimated from lower thickness of inner retinal layers, was associated with incident all-cause dementia and Alzheimer's disease (AD).

Methods: We performed an individual participant data meta-analysis using unpublished data from four prospective cohort studies with a total of 69,955 participants (n = 1087 cases of incident all-cause dementia; n = 520 cases incident AD; follow-up time median [interquartile range] 11.3 [8.8-11.5] years).

Results: General baseline characteristics of the study population were mean (standard deviation) age, 58.1 (8.8) years; 47% women. After adjustment, lower baseline macular retinal nerve fiber layer thickness was significantly associated with a 10% and 11% higher incidence of all-cause dementia and AD, respectively. Lower baseline macular ganglion cell-inner plexiform layer thickness was not significantly associated with these outcomes.

Discussion: These findings suggest that retinal neurodegeneration precedes the onset of clinical dementia. Retinal imaging tools may be informative biomarkers for the study of the early pathophysiology of dementia.

Keywords: Alzheimer's disease; E3 consortium; OCT; The Alienor Study; The Maastricht Study; The Tromsø Study; The UK Biobank; UK Biobank Eye & Vision Consortium; dementia; early-onset dementia cohort; epidemiology; frontotemporal dementia; optical coherence tomography; retinal imaging; retinal neurodegeneration; vascular dementia.

Publication types

  • Meta-Analysis

MeSH terms

  • Alzheimer Disease* / complications
  • Alzheimer Disease* / diagnostic imaging
  • Alzheimer Disease* / epidemiology
  • Data Analysis
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Retina / diagnostic imaging
  • Tomography, Optical Coherence* / methods