ArticleJournal of Alzheimer's disease : JAD2022
Longitudinal Associations of Plasma TMAO and Related Metabolites with Cognitive Impairment and Dementia in Older Adults: The Cardiovascular Health Study.
Article in Journal of Alzheimer's disease : JAD, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
4 citing papers in PubMed, 1 synthesis or guideline pooled it, 6 citations in OpenAlex.
- Association of trimethylamine oxide and its precursors with cognitive impairment: a systematic review and meta-analysis.Frontiers in aging neuroscience · 2024Pooled it
- Trimethylamine-N-oxide (TMAO) and risk of incident cardiovascular events in the multi ethnic study of Atherosclerosis.Scientific reports · 2025Article
- Decoding TMAO in the Gut-Organ Axis: From Biomarkers and Cell Death Mechanisms to Therapeutic Horizons.Drug design, development and therapy · 2025Review
- Plasma trimethylamine N-oxide (TMAO): associations with cognition, neuroimaging, and dementia.Alzheimer's research & therapy · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 10 institutions in 3 countries.
Funding
Abstract
backgroundAnimal studies suggest that gut microbiome metabolites such as trimethylamine N-oxide (TMAO) may influence cognitive function and dementia risk. However potential health effects of TMAO and related metabolites remain unclear.
objectiveWe examined prospective associations of TMAO, γ-butyrobetaine, crotonobetaine, carnitine, choline, and betaine with risk of cognitive impairment and dementia among older adults aged 65 years and older in the Cardiovascular Health Study (CHS).
methodsTMAO and metabolites were measured in stored plasma specimens collected at baseline. Incident cognitive impairment was assessed using the 100-point Modified Mini-Mental State Examination administered serially up to 7 times. Clinical dementia was identified using neuropsychological tests adjudicated by CHS Cognition Study investigators, and by ICD-9 codes from linked Medicare data. Associations of each metabolite with cognitive outcomes were assessed using Cox proportional hazards models.
resultsOver a median of 13 years of follow-up, 529 cases of cognitive impairment, and 522 of dementia were identified. After multivariable adjustment for relevant risk factors, no associations were seen with TMAO, carnitine, choline, or betaine. In contrast, higher crotonobetaine was associated with 20-32% higher risk of cognitive impairment and dementia per interquintile range (IQR), while γ-butyrobetaine was associated with ∼25% lower risk of the same cognitive outcomes per IQR.∥Conclusion:These findings suggest that γ-butyrobetaine, crotonobetaine, two gut microbe and host metabolites, are associated with risk of cognitive impairment and dementia. Our results indicate a need for mechanistic studies evaluating potential effects of these metabolites, and their interconversion on brain health, especially later in life.
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What OpenQuestion holds
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.