Z. Zhang, M. Hu, Z. Teng, Y. Mu and P. Yin (2026). Joint association of a healthy low-carbohydrate diet and frailty with the risk of incident Alzheimer's disease and vascular dementia: a prospective cohort study. Frontiers in public health, 14, 1853648. https://doi.org/10.3389/fpubh.2026.1853648

PubMed 42368914

[Abstract]
BACKGROUND: We aimed to investigate the associations between a healthy low-carbohydrate diet (HLCD) score, frailty and their combined effects with the risk of Alzheimer's disease (AD) and vascular dementia (VD).

METHODS: This cohort study analyzed 157,465 participants from the UK Biobank. The HLCD score was calculated based on the intake of total carbohydrates, vegetable proteins, and unsaturated fats, while frailty was assessed using a frailty index incorporating a wide range of biological systems and physical capacities, including sensory functions, mental health, and systemic comorbidities, which was developed and validated by the UK Biobank. Cox proportional hazards models and restricted cubic splines were employed for analysis.

RESULTS: Higher HLCD scores were significantly associated with a lower risk of AD (Q4 vs. Q1: HR = 0.66; 95% CI: 0.52-0.84) and VD (Q4 vs. Q1: HR = 0.54; 95% CI: 0.39-0.75). Frailty was identified as a risk factor for both dementia subtypes. Compared with the nonfrail group, the adjusted HRs for AD were 1.33 (1.08-1.65) for prefrail and 1.62 (1.33-1.98) for frail groups, while the adjusted HRs for VD were 1.61 (1.20-2.17) for prefrail and 2.46 (1.89-3.20) for frail groups. In the joint association analysis, adherence to a high-quality HLCD effectively mitigates the increased risk of AD attributed to frailty. Frail individuals with high HLCD scores exhibited a significantly lower risk of AD compared to those with low HLCD scores (HR = 0.63, 95% CI: 0.47-0.85). For VD, the protective benefit was more pronounced in the prefrailty stage (HR = 0.52, 0.35-0.79) than in the frail stage (HR = 0.83, 0.59-1.17).

CONCLUSIONS: High adherence to the HLCD was associated with a lower risk of AD and VD, whereas frailty independently was associated with an increased the risk of AD and VD. Adherence to a high-quality HLCD effectively mitigates the increased risk associated with frailty. Promoting healthy low-carbohydrate diets may serve as a robust strategy to enhance cognitive resilience in older populations.