Association of dietary choline intake with cognitive decline and related outcomes: a systematic review and dose-response meta-analysis of observational studies.

Cognitive decline is a growing global public health concern in aging populations, with genetic and dietary factors contributing to individual differences in cognitive trajectories. Dietary choline, as a precursor of acetylcholine and a key regulator of methylation and membrane integrity, may protect cognitive function. However, epidemiological evidence remains inconsistent, and the optimal intake for neuroprotection remains unclear. This study aimed to evaluate the association between dietary choline intake and cognitive decline and related outcomes, and a dose-response meta-analysis was performed. Eligible studies reporting risk estimates for cognitive decline, mild cognitive impairment (MCI), or related outcomes according to dietary choline intake were included. Study characteristics and outcomes were extracted. Pooled odds ratios (ORs) were estimated using a random-effects model and dose-response associations were assessed using a two-stage generalized least-squares framework. Eleven articles were included, of which nine independent cohorts involving 218 378 participants contributed to the primary meta-analysis. Higher dietary choline intake was significantly associated with a lower risk of adverse cognitive outcomes (pooled OR = 0.76, 95% CI: 0.63-0.92) and cognitive impairment/decline (pooled OR = 0.67, 95% CI: 0.47-0.95). A significant inverse association was also observed for Alzheimer's disease (AD) (pooled OR = 0.74, 95% CI: 0.55-0.99), whereas the association with dementia was not statistically significant. Dose-response analyses revealed significant nonlinear associations for adverse cognitive outcomes and cognitive impairment/decline, with the lowest risk observed at approximately 350-400 mg day^-1 of dietary choline intake. Dietary choline intake was associated with lower risks of adverse cognitive outcomes, cognitive impairment/decline, and AD, with the lowest risks observed at moderate intake levels. These findings highlight the potential importance of adequate choline intake for cognitive health.