Dietary choline intake and incident dementia in middle-aged and older adults: a prospective cohort study and dose–response meta-analysis

BACKGROUND: Choline plays key roles in neurotransmitter synthesis and membrane integrity, processes fundamental to brain function. However, evidence from population studies on the association of dietary choline intake with dementia risk is mixed. METHODS: We analyzed data of 5,301 dementia-free participants (mean age = 68.6 years; 59% females) in the Health and Retirement Study and followed them through 2022. Dietary choline intake was assessed with a validated food frequency questionnaire (2013-2014) and energy-adjusted using the residual method. Incident dementia was identified with the Langa-Weir algorithm. Cox models estimated hazard ratios (HRs) across quintiles of total intake of choline and its contributing components. We additionally conducted a dose-response meta-analysis of existing prospective cohorts using a two-stage random-effects model with restricted cubic splines. RESULTS: During follow-up (median = 8.4 years, interquartile range: 6.4-8.9 years), 506 individuals developed dementia. Total choline intake showed a non-linear association with dementia risk. Compared with the lowest quintile, the multivariable-adjusted HRs (95% CI) for incident dementia across increasing quintiles of total choline were 0.88 (0.66-1.17), 0.87 (0.65-1.17), 0.68 (0.49-0.92), and 0.91 (0.66-1.25) (P-linear-trend: 0.198, P-non-linearity: 0.024). Among choline contributing components, moderate phosphatidylcholine and sphingomyelin intake levels were inversely associated with dementia risk (HR comparing quintile 4 to 1: 0.62, 95%CI: 0.46-0.84 and 0.70, 0.52-0.94, respectively). The meta-analysis of five cohorts (137,607 participants, 2459 dementia cases) showed an L-shaped association of dietary choline intake with dementia risk (P-linear-trend: 0.003, P-non-linearity: 0.036) with a turning point at 465 mg/day. CONCLUSIONS: In this prospective cohort study and dose-response meta-analysis, moderate dietary choline intake was associated with a lower risk of incident dementia in middle-aged and older adults. These findings support further investigation of choline in relation to cognitive aging, particularly the potential non-linear association. REGISTRY FOR META-ANALYSES: CRD420251151642.