Associations of inner retinal layers with risk of incident dementia: An individual participant data analysis of four prospective cohort studies.
van der Heide FCT., Khawaja A., Berendschot TTJM., Littlejohns TJ., Kuźma E., Luben R., Patel PJ., Foster PJ., Maastricht Study Consortium None., Bertelsen G., von Hanno T., Johnsen B., Schirmer H., Rebouças SCL., Grasset L., Delcourt C., Helmer C., UK Biobank Eye & Vision Consortium None., E3 consortium None., Stehouwer CDA.
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 METHODS: We performed an individual participant data meta-analysis using unpublished data from four prospective cohort studies with a total of 69,955 participants (n = 1087 cases of incident all-cause dementia; n = 520 cases incident AD;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.