ArticleAmerican journal of epidemiology2021
Extension of Mendelian Randomization to Identify Earliest Manifestations of Alzheimer Disease: Association of Genetic Risk Score for Alzheimer Disease With Lower Body Mass Index by Age 50 Years.
Article in American journal of epidemiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Challenges in interpreting Mendelian randomization studies with a disease as the exposure: Using COVID-19 liability studies as an exemplar.European journal of human genetics : EJHG · 2025Pooled it
- Dementia risk across distinct metabolic profiles in the UK Biobank.GeroScience · 2026Article
- The association of Alzheimer's disease genetic risk with social connectedness in middle- and older ages.American journal of epidemiology · 2026Article
- An Introduction to Longitudinal Synthetic Cohorts for Studying the Life Course Drivers of Health Outcomes and Inequalities in Older Age.Current epidemiology reports · 2025Article
- Advances in Genetic Risk Scores for Alzheimer's Disease and Dementia: A Systematic Review.Neurology international · 2025Review
- Causal cardiovascular risk factors for dementia: insights from observational and genetic studies.Cardiovascular research · 2025Review
- Article
- Adiponectin Gene Polymorphisms: A Case-Control Study on Their Role in Late-Onset Alzheimer's Disease Risk.Life (Basel, Switzerland) · 2024Article
- Genetic risk score for Alzheimer's disease predicts brain volume differences in mid and late life in UK biobank participants.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- A bidirectional Mendelian randomisation study to evaluate the relationship between body constitution and hearing loss.Scientific reports · 2023Article
- Snoring and risk of dementia: a prospective cohort and Mendelian randomization study.medRxiv : the preprint server for health sciences · 2023Article
- Modifiable cardiovascular risk factors and genetics for targeted prevention of dementia.European heart journal · 2023Article
- Genetic Associations Between Modifiable Risk Factors and Alzheimer Disease.JAMA network open · 2023Article
- Genetically proxied lean mass and risk of Alzheimer's disease: mendelian randomisation study.BMJ medicine · 2023Article
- Associations Between Handgrip Strength and Dementia Risk, Cognition, and Neuroimaging Outcomes in the UK Biobank Cohort Study.JAMA network open · 2022Article
- Association of Genetic Variants Linked to Late-Onset Alzheimer Disease With Cognitive Test Performance by Midlife.JAMA network open · 2022Article
- Weight loss in a cardiovascular trial population identifies people at future risk of dementia.Alzheimer's & dementia (Amsterdam, Netherlands) · 2022Article
- Methods to Address Self-Selection and Reverse Causation in Studies of Neighborhood Environments and Brain Health.International journal of environmental research and public health · 2021Review
- Individual and Combined Associations of Glucose Metabolic Components With Cognitive Function Modified by Obesity.Frontiers in endocrinology · 2021Article
- The association of cholesterol levels with memory and memory change over a 14-year period in a US national cohort.Alzheimer's & dementia (New York, N. Y.)Article
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9 authors.
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Abstract
Weight loss or lower body mass index (BMI) could be an early symptom of Alzheimer disease (AD), but when this begins to emerge is difficult to estimate with traditional observational data. In an extension of Mendelian randomization, we leveraged variation in genetic risk for late-onset AD risk to estimate the causal effect of AD on BMI and the earliest ages at which AD-related weight loss (or lower BMI as a proxy) occurs. We studied UK Biobank participants enrolled in 2006-2010, who were without dementia, aged 39-73, with European genetic ancestry. BMI was calculated with measured height/weight (weight (kg)/height (m)2). An AD genetic risk score (AD-GRS) was calculated based on 23 genetic variants. Using linear regressions, we tested the association of AD-GRS with BMI, stratified by decade, and calculated the age of divergence in BMI trends between low and high AD-GRS. AD-GRS was not associated with BMI in 39- to 49-year-olds (β = 0.00, 95% confidence interval (CI): -0.03, 0.03). AD-GRS was associated with lower BMI in 50- to 59-year-olds (β = -0.03, 95% CI: -0.06, -0.01) and 60- to 73-year-olds (β = -0.09, 95% CI:-0.12, -0.07). Model-based BMI age curves for high versus low AD-GRS began to diverge after age 47 years. Sensitivity analyses found no evidence for pleiotropy or survival bias. Longitudinal replication is needed; however, our findings suggest that AD genes might begin to reduce BMI decades prior to dementia diagnosis.
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