ArticleNature medicine2025
Interplay of genetic predisposition, plasma metabolome and Mediterranean diet in dementia risk and cognitive function.
Article in Nature medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Research progress and hotspots of the impact of Mediterranean diet on brain health from 2005 to 2025: a bibliometric and visualization analysis.Frontiers in nutrition · 2026Pooled it
- Global research trends and hotspots of short-chain fatty acids in cognitive impairment: a bibliometric analysis based on two databases.Frontiers in medicine · 2026Pooled it
- Pooled it
- Polygenicity and APOE ε4 shape response to intervention in mild cognitive impairment.Alzheimer's research & therapy · 2025Trial
- Review
- Divergent biological consequences of APOE isoforms across industrialized and non-industrial environments.PLoS genetics · 2026Article
- APOE4-AGE axis is linked to mtDNA release and cGAS-STING-mediated neuroinflammation in the aging brain.Free radical biology & medicine · 2026Article
- Beyond Diagnosis: Characterising Symptom Profiles of Dementia in a Resource-Limited South African Clinical Setting.Healthcare (Basel, Switzerland) · 2026Article
- Chronic schizophrenia versus Alzheimer's disease: neuroimaging perspectives on the late-life course of schizophrenia.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Seipin modulates Alzheimer's disease pathogenesis by regulating ferroptosis through a glycine-mediated metabolic pathway.Metabolic brain disease · 2026Article
- KetoFLEX 12/3 Diet and Cognitive Health: A Precision-Nutrition Perspective on Mechanisms, Emerging Evidence, and Future Directions.Nutrients · 2026Review
- The association between PMEnvironmental research · 2026Article
- The mechanisms and strategies for Alzheimer's disease prevention: An update.Acta pharmaceutica Sinica. B · 2026Review
- Reproductive history differentially shapes the neural response of middle-aged hAPOEɛ4 female rats to estradiol therapy after a metabolic challenge.Biology of sex differences · 2026Article
- Beneficial Effects of Olive Oil and the Mediterranean Diet on Alzheimer's Disease and Vascular Dementia: A Review.Medicina (Kaunas, Lithuania) · 2026Review
- Dietary Whole Wheat Flour Intake in Pakistan: A Cross-Sectional Insight into Long-Term Dementia Prevention.Nutrients · 2026Article
- Long-term adherence and changes in the Mediterranean and MIND diets in relation to dementia risk and cognitive function.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Divergent Biological Consequences of APOE Isoforms Across Industrialized and Non-Industrial Environments.bioRxiv : the preprint server for biology · 2026Article
- Plasma Proteomic Analysis ofmedRxiv : the preprint server for health sciences · 2026Article
- Immunometabolism Reframes Alzheimer's Disease: From Systemic Dysmetabolism to Glial Rewiring.Cellular and molecular neurobiology · 2026Review
Corrections and comments
- Erratum issued
Authors and funding
20 authors.
Funding
Abstract
Alzheimer's disease (AD) and AD-related dementias (AD/ADRD) have a substantial genetic basis, with APOE4 homozygotes increasingly recognized as a distinct genetic subtype. To identify genotype-specific metabolic pathways and modifiable risk factors, we integrated genetic, plasma metabolomic and dietary data from 4,215 women and 1,490 men in prospective cohorts. Here we show that the associations of 57 metabolites with dementia risk varied by APOE4 genotype or other AD/ADRD risk variants. For example, cholesteryl esters and sphingomyelins were most strongly associated with increased dementia risk in APOE4 homozygotes, whereas inverse associations with glycerides were specific to this genotype. Dimethylguanidino-valeric acid was more strongly associated with dementia risk among carriers of the rs2154481-C allele (APP). Adherence to the Mediterranean diet more effectively modulated dementia-related metabolites in APOE4 homozygotes, suggesting targeted prevention strategies. Incorporating metabolomic data modestly improved dementia risk prediction, particularly during early follow-up. Mendelian randomization analysis identified 19 putative causal relationships between metabolites and cognitive outcomes, including protective effects of 4-guanidinobutanoate, carotenoids and N
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.