Novel retinal imaging biomarkers for cognitive decline: abridged secondary publication
CY Cheung1, VTT Chan1, LWC Au2, CC Tham1, TCY Kwok2, CTV Mok2
1 Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
2 Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
  1. There has been a search for Alzheimer disease (AD) biomarkers that facilitate early disease diagnosis while being non-invasive, widely available, and reliable. The retina, an extension of the central nervous system, offers a “window” for in vivo studies of the cerebral microvascular and neurodegenerative damage in AD.
  2. In this prospective observational study, healthy controls and patients with AD or amnestic mild cognitive impairment underwent neuropsychological testing, retinal imaging, and neuroimaging to explore the associations of retinal changes with upstream pathological changes in AD and cognitive decline.
  3. Compared with amyloid-β-negative individuals, amyloid-β-positive individuals had significantly thinner macular ganglion-cell inner plexiform layer thickness. Among amyloid-β-positive individuals, cognitively impaired individuals had significantly larger foveal avascular zone area, smaller fractal dimension, smaller skeleton density, larger vessel diameter index, and smaller inter-capillary area, compared with cognitively normal individuals. Global amyloid burden was associated with macular ganglion-cell inner plexiform layer thickness and foveal avascular zone area.
  4. Central subfield thickness and mean cube thickness were associated with the progression of cognitive decline over 12 months.
  5. Specific retinal microvascular abnormalities and retinal neuronal/axonal loss, measured using non-invasive retinal imaging technologies, may reflect cerebrovascular dysfunction and classic features of neuronal injury in the AD brain; moreover, they are associated with AD and can independently predict cognitive decline.