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Research Article: Nonlinear L-shaped association between composite dietary antioxidant index and risk of dementia: a prospective cohort study

Date Published: 2026-07-03

Abstract:
Dietary intake of antioxidants may decrease risk of dementia. However, the relationship between the composite dietary antioxidant index (CDAI) and dementia, has not yet been explored. This study investigated the relationship between CDAI and risk of dementia and to explore potential mediators of the relationship. Data were extracted from the prospective UK Biobank on 157,742 dementia-free participants, who were followed up for a median of 13.39 yr. Potential associations between CDAI at enrollment and subsequent development of all-cause dementia, Alzheimer's dementia or vascular dementia were assessed using Cox proportional hazards regression. Potential non-linear associations were explored using restricted cubic spline analysis. Exploratory analyses were performed to assess whether blood inflammatory markers and cortical/subcortical gray matter volumes accounted for part of the associations, using multivariable linear regression and mediation analyses. During follow-up, 791 people developed Alzheimer's dementia, 322 developed vascular dementia, and 709 developed other types of dementia. Higher CDAI was significantly associated with lower risk of all-cause dementia and Alzheimer's dementia, and the association was stronger in women than in men (p for interaction < 0.05). The association was nonlinear and L-shaped (nonlinear p ? 0.001), with inflection points at 1.579 for all-cause dementia and 0.848 for Alzheimer's dementia. At CDAIs below these inflection points, each unit increase in CDAI was associated with 6.3% lower risk of all-cause dementia (HR 0.937, 95% CI 0.907–0.968, P < 0.001) and 6.5% lower risk of Alzheimer's dementia (HR 0.935, 95% CI 0.897–0.974, P = 0.001). Exploratory pathway analyses suggested that neutrophil and lymphocyte percentages modestly accounted for the association between CDAI and risk of all-cause dementia and Alzheimer's dementia. CDAI may relate to risk of dementia in an L-shaped manner. Exploratory analyses suggested a possible role of systemic inflammation in this association.

Introduction:
Dementia, a leading cause of disability and dependency in older adults, imposes a heavy burden on families and society as the global population ages ( 1 ). Alzheimer's dementia and vascular dementia are the most common subtypes, accounting for 60%?80% and 10%?20% of dementia cases, respectively ( 2 ). Fourteen modifiable risk factors for dementia have been identified by the Lancet Commission, including oxidative stress ( 3 ). Oxidative stress could trigger a cascade of cellular damage in the brain that…

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