SynthesisJournal of Alzheimer's disease : JAD2018
Which Risk Factors Causally Influence Dementia? A Systematic Review of Mendelian Randomization Studies.
Synthesis in Journal of Alzheimer's disease : JAD, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 6 of them syntheses 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
34 citing papers in PubMed, 6 syntheses or guidelines pooled it.
- Structured tools for assessing quality and risk of bias in Mendelian randomization studies: an updated systematic review.International journal of epidemiology · 2026Pooled it
- Alcohol consumption and its association with cancer, cardiovascular, liver and brain diseases: a systematic review of Mendelian randomization studies.Frontiers in epidemiology · 2024Pooled it
- Tools for assessing quality and risk of bias in Mendelian randomization studies: a systematic review.International journal of epidemiology · 2023Pooled it
- Impact of glucose on risk of dementia: Mendelian randomisation studies in 115,875 individuals.Diabetologia · 2020Pooled it
- Role of Vitamin D in Preventing and Treating Selected Extraskeletal Diseases-An Umbrella Review.Nutrients · 2020Pooled it
- Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing.Nature genetics · 2019Pooled it
- Dietary Patterns, Micronutrient Adequacy, and Metabolic Vulnerability in Alzheimer's Disease: A Critical Narrative Review.Nutrients · 2026Review
- Modifiable and clinically actionable exposures for vascular dementia: a structured evidence synthesis of Mendelian randomization studies.Journal of neurology · 2026Review
- Sleep and dementia: Assessing established dementia-related factors using multivariable Mendelian randomization.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Feasibility of identifying factors related to Alzheimer's disease and related dementia in real-world data.JAMIA open · 2026Review
- Alcohol-Induced Dysregulation of Hydrogen Sulfide Signaling in Alzheimer's Disease-International journal of molecular sciences · 2026Review
- A Causal Association Between Drug Use and Cognitive Impairment: A Two-Sample Mendelian Randomization Study.Brain and behavior · 2025Article
- Modifiable dementia risk factors associated with objective and subjective cognition.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Characterizing the progression from mild cognitive impairment to dementia: a network analysis of longitudinal clinical visits.BMC medical informatics and decision making · 2024Article
- The impact of maternal smoking during pregnancy and the age of smoking initiation on incident dementia: A prospective cohort study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Entertainment activities and the risk of Alzheimer's disease: a Mendelian randomization analysis.Frontiers in aging neuroscience · 2024Article
- Article
- Artificial intelligence for dementia genetics and omics.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Review
- Artificial intelligence for dementia prevention.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Review
- Metabolic Overlap between Alzheimer's Disease and Metabolic Syndrome Identifies theInternational journal of molecular sciences · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
Abstract
backgroundNumerous risk factors for dementia are well established, though the causal nature of these associations remains unclear.
objectiveTo systematically review Mendelian randomization (MR) studies investigating causal relationships between risk factors and global cognitive function or dementia.
methodsWe searched five databases from inception to February 2017 and conducted citation searches including MR studies investigating the association between any risk factor and global cognitive function, all-cause dementia or dementia subtypes. Two reviewers independently assessed titles and abstracts, full-texts, and study quality.
resultsWe included 18 MR studies investigating education, lifestyle factors, cardiovascular factors and related biomarkers, diabetes related and other endocrine factors, and telomere length. Studies were of predominantly good quality, however eight received low ratings for sample size and statistical power. The most convincing causal evidence was found for an association of shorter telomeres with increased risk of Alzheimer's disease (AD). Causal evidence was weaker for smoking quantity, vitamin D, homocysteine, systolic blood pressure, fasting glucose, insulin sensitivity, and high-density lipoprotein cholesterol. Well-replicated associations were not present for most exposures and we cannot fully discount survival and diagnostic bias, or the potential for pleiotropic effects.
conclusionsGenetic evidence supported a causal association between telomere length and AD, whereas limited evidence for other risk factors was largely inconclusive with tentative evidence for smoking quantity, vitamin D, homocysteine, and selected metabolic markers. The lack of stronger evidence for other risk factors may reflect insufficient statistical power. Larger well-designed MR studies would therefore help establish the causal status of these dementia risk factors.
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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.