Observational studyNeurobiology of disease2024
MRI-derived brain iron, grey matter volume, and risk of dementia and Parkinson's disease: Observational and genetic analysis in the UK Biobank cohort.
Observational study in Neurobiology of disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Human Leukocyte Antigen and microRNAs as Key Orchestrators of Mild Cognitive Impairment and Alzheimer's Disease: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Genetic architecture of MRI-derived cervical spinal cord morphology reveals sensory-motor axis and systemic disease associations.Nature communications · 2026Article
- Susceptibility Source Separation Unveils Paramagnetic and Diamagnetic Trajectories in Healthy Brains From 5 to 90 Years.NMR in biomedicine · 2026Article
- Plasma GDF15 affects long-term dementia risk and alters neuroimmune signaling.Science advances · 2026Article
- Programmed cell death: a promising management for Alzheimer's disease.Apoptosis : an international journal on programmed cell death · 2026Review
- The spleen-brain axis in Alzheimer's disease and related dementias: Integrating immune and metabolic regulation.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Multimodal non-invasive approaches for early Alzheimer's disease detection: a review of neuroelectrophysiological and neuroimaging techniques.Frontiers in psychiatry · 2026Review
- Haemochromatosis Genotypes and Incident Dementia in a Prospective Study of Older Adults.Neurology · 2025Article
- Genetic Markers of Postmortem Brain Iron.Journal of neurochemistry · 2025Article
- Causal associations between iron levels in subcortical brain regions and psychiatric disorders: a Mendelian randomization study.Translational psychiatry · 2025Article
- Brain Iron Deposition Alterations in Type 2 Diabetes Mellitus Patients With Mild Cognitive Impairment Based on Quantitative Susceptibility Mapping.Journal of diabetes · 2025Observational
- A review of studies on vascular dementia and iron metabolism.Science progressReview
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Authors and funding
10 authors.
Funding
Abstract
backgroundIron overload is observed in neurodegenerative diseases, especially Alzheimer's disease (AD) and Parkinson's disease (PD). Homozygotes for the iron-overload (haemochromatosis) causing HFE p.C282Y variant have increased risk of dementia and PD. Whether brain iron deposition is causal or secondary to the neurodegenerative processes in the general population is unclear.
methodsWe analysed 39,533 UK Biobank participants of European genetic ancestry with brain MRI data. We studied brain iron estimated by R2* and quantitative susceptibility mapping (QSM) in 8 subcortical regions: accumbens, amygdala, caudate, hippocampus, pallidum, putamen, substantia nigra, and thalamus. We performed genome-wide associations studies (GWAS) and used Mendelian Randomization (MR) methods to estimate the causal effect of brain iron on grey matter volume, and risk of AD, non-AD and PD. We also used MR to test whether genetic liability to AD or PD causally increased brain iron (R2* and QSM).
findingsIn GWAS of R2* and QSM we replicated 83% of previously reported genetic loci and identified 174 further loci across all eight brain regions. Higher genetically predicted brain iron, using both R2* and QSM, was associated with lower grey matter volumes in the caudate, putamen and thalamus (e.g., Beta-putamenQSM: -0.37, p = 2*10-46). Higher genetically predicted thalamus R2* was associated with increased risk of non-AD dementia (OR 1.36(1.16;1.60), p = 2*10-4) but not AD (p > 0.05). In males, genetically predicted putamen R2* increased non-AD dementia risk, but not in females. Higher genetically predicted iron in the caudate, putamen, and substantia nigra was associated with an increased risk of PD (Odds Ratio QSM ∼ substantia-nigra 1.21(1.07;1.37), p = 0.003). Genetic liability to AD or PD was not associated with R2* or QSM in the dementia or PD-associated regions.
interpretationOur genetic analysis supports a causal effect of higher iron deposition in specific subcortical brain regions for Parkinson's disease, grey matter volume, and non-Alzheimer's dementia.
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