Multiple Demographic, Lifestyle, and Biological Factors Associated With Brain Iron Deposition in the Basal Ganglia: A Comprehensive Analysis of 25,980 UK Biobank Participants

Background

The susceptibility values of the basal ganglia reflect the health status of these nuclei. We aimed to explore the associations between various demographic characteristics, lifestyle factors, and biological factors that have the potential to contribute to magnetic susceptibility and investigate the comprehensive impact of these multiple factors on basal ganglia susceptibility values.

Methods

We included 25,980 participants from the UK Biobank. Linear regression analysis was employed to assess the relationship between basal ganglia susceptibility values and demographic characteristics (age, sex, ethnicity), lifestyle factors (tea consumption, coffee intake, smoking status, alcohol consumption, physical activity, insomnia status), and biological factors (C-reactive protein, blood cell counts, anthropometric measures, blood pressure parameters).

Results

Multiple factors demonstrated significant associations with basal ganglia iron deposition. Among biological factors, C-reactive protein showed significant positive correlations with susceptibility values in the caudate nucleus (β = 0.028, p < 0.001), globus pallidus (β = 0.046, p < 0.001), and substantia nigra (β = 0.031, p < 0.001). Waist circumference, another biological measure, had substantial positive effects on most basal ganglia regions (β = 0.115 in caudate, β = 0.122 in putamen, β = 0.058 in globus pallidus). Among lifestyle factors, current smoking status was significantly associated with increased susceptibility values across all four basal ganglia nuclei (β = 0.053–0.061, all p < 0.001). Tea consumption demonstrated dose-dependent protective effects, with daily consumption of ≥ 4 cups showing significant negative associations with all basal ganglia regions (−0.032 to −0.093 standard deviations). Age demonstrated significant positive associations with most basal ganglia regions. Gender differences were observed in tea consumption effects, with females showing stronger protective benefits (5.59 vs. 1.50 years of equivalent “rejuvenation” effect for 0–3 cups daily).

Conclusions

We provide evidence for multiple demographic, lifestyle, and biological factors influencing brain iron deposition in healthy middle-aged and elderly individuals. Systemic inflammation, smoking, and increased adiposity were associated with greater iron deposition, while tea consumption showed protective effects. These findings highlight potential targets for interventions aimed at maintaining brain health.

Ethics approval and consent to participate

The UK Biobank protocol was approved by the NHS North West Multicentre Research Ethics Committee (21/NW/0157). All participants provided informed consent at recruitment, allowing for follow-up using data linkage to health records.