Measures of retinal health successfully capture risk for Alzheimer's disease and related dementias at midlife.

Background: Identification of at-risk individuals who would benefit from early intervention for Alzheimer's disease and related dementias (ADRD) is critical as new treatments are developed. Measures of retinal health could offer accessible and low-cost indication of pre-morbid disease risk, but their association with ADRD risk is unknown.

Objective: To determine whether midlife retinal neuronal and microvascular measures are associated with ADRD risk-index scores and individual domains of ADRD risk.

Methods: Data were from the Dunedin Multidisciplinary Health and Development Study, a population-representative longitudinal New Zealand-based birth cohort study. 94.1% (N = 938) of living Study members were seen at age 45 (2017-2019). Retinal neuronal (retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL)) and microvascular (arterioles and venules) measures were used as predictors. Outcome measures were four top ADRD risk indexes (CAIDE, LIBRA, Lancet, and ADU-ADRI), and a comprehensive midlife ADRD risk index, the DunedinARB.

Results: Poorer retinal microvascular health (narrower arterioles and wider venules) was associated with greater ADRD risk (βs = 0.16-0.31; ps < 0.001). Thinner RNFL was modestly associated with higher ADRD risk (βs = 0.05-0.08; ps = 0.02-0.13). Follow-up tests of distinct domains of ADRD risk indicated that while RNFL associations reflected cardiometabolic risk only, microvascular measures were associated with diverse ADRD risk factors.

Conclusions: Measures of retinal health, particularly microvascular measures, successfully capture ADRD risk across several domains of known risk factors, even at the young midlife age of 45 years. Retinal microvascular imaging may be an accessible, scalable, and relatively low-cost method of assessing ADRD risk among middle-aged adults.