AbstractBackgroundCarotenoids are vegetable pigments uniquely provided by diet which have antioxidant, immunomodulatory and specific neuroprotective properties. Carotenes (found in orange‐yellow fruits and vegetables) are precursors of retinoids, key signaling molecules for synaptic plasticity. The xanthophylls, lutein and zeaxanthin (found in green vegetables, orange‐yellow fruits and corn) cross the blood‐brain barrier, may decrease lipid peroxidation and stabilize lipid‐protein structures in neuronal membranes. Limited epidemiological studies on dietary carotenoids (assessed by questionnaires) reported inconsistent associations with brain aging using cognitive change as an outcome (and not neuroimaging or clinical dementia or Alzheimer’s disease diagnosis). However, blood carotenoids levels were associated with lower risk of dementia over 10 years, in a large cohort of older adults, the Three‐City (3C) study. Here, we further investigated whether blood carotenoids were also associated with the 10‐year atrophy of the medial temporal lobe (MTL), a central biomarker of neurodegeneration in aging.MethodWe included 461 dementia‐free participants from the 3C study (age ≥65), who had plasma carotenoid (α and β‐carotene, lycopene, lutein, zeaxanthin, β‐cryptoxanthin) measures at baseline and who underwent at least one of the three repeated brain imaging exams performed in the subsequent 10 years. Linear mixed models were used to assess the association between plasma carotenoids and MTL volume change assessed using FreeSurfer 5.1 segmentation software.ResultOver a median follow‐up of 5.1 years (maximum 11.8 years), higher plasma levels of total carotenoids and of β‐carotene were associated with lower decline in MTL volume (P = .04 and P = .008, respectively). The mean differences in MTL volume change for each increase of 1 SD were 0.02 (95% CI, 0.001; 0.04) cm3/year and 0.02 (0.01; 0.04) cm3/year for total carotenoids and β‐carotene, respectively. Other carotenoids were not significantly associated with MTL atrophy.ConclusionThe associations found between plasma total carotenoids and β‐carotene and 10‐year atrophy of the MTL in this large cohort of older adults suggest a beneficial role of carotenoids for the prevention of age‐related neurodegeneration.