ArticleJournal of Alzheimer's disease : JAD2021
Segmented Linear Mixed Model Analysis Reveals Association of the APOEɛ4 Allele with Faster Rate of Alzheimer's Disease Dementia Progression.
Article in Journal of Alzheimer's disease : JAD, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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
19 citing papers in PubMed, 20 citations in OpenAlex.
- Article
- APOE genotype differentially modulates prion pathology in a mouse model.Acta neuropathologica communications · 2026Article
- APOE Genotype Differentially Modulates Prion Pathology in a Mouse Model.Research square · 2025Article
- Apolipoprotein ε4 exacerbates white matter impairment in a mouse model of Aβ amyloidosis by decreasing actively myelinating oligodendrocytes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- The economic burden of subjective cognitive decline, mild cognitive impairment and Alzheimer's dementia: excess costs and associated clinical and risk factors.Alzheimer's research & therapy · 2025Article
- Interrupted Learning across the Lifespan.Human development · 2025Article
- Retrosplenial hypometabolism precedes the conversion from mild cognitive impairment to Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Article
- Lower mortality risk in APOE4 carriers with normal cognitive ageing.Scientific reports · 2023Article
- Interaction betweenGenes · 2023Article
- Mapping cerebral atrophic trajectory from amnestic mild cognitive impairment to Alzheimer's disease.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- Neuropathology-Independent Association BetweenNeurology. Genetics · 2023Article
- Integrated partially linear model for multi-center studies with heterogeneity and batch effect in covariates.Statistics · 2023Article
- Investigating the temporal pattern of neuroimaging-based brain age estimation as a biomarker for Alzheimer's Disease related neurodegeneration.NeuroImage · 2022Article
- Genetic polymorphisms of apolipoprotein E in nonarteritic anterior ischemic optic neuropathy.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2022Article
- Cognitive Function among World Trade Center-Exposed Community Members with Mental Health Symptoms.International journal of environmental research and public health · 2022Article
- Apolipoprotein E4 Effects a Distinct Transcriptomic Profile and Dendritic Arbor Characteristics in Hippocampal Neurons CulturedFrontiers in aging neuroscience · 2022Article
- Association between the APOE gene polymorphism and lipid profile and the risk of atrial fibrillation.Lipids in health and disease · 2021Article
- Absence of Apolipoprotein E is associated with exacerbation of prion pathology and promotes microglial neurodegenerative phenotype.Acta neuropathologica communications · 2021Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAPOEɛ4 allele carriers present with an increased risk for late-onset Alzheimer's disease (AD), show cognitive symptoms at an earlier age, and are more likely to transition from mild cognitive impairment (MCI) to dementia but despite this, it remains unclear whether or not the ɛ4 allele controls the rate of disease progression.
objectiveTo determine the effects of the ɛ4 allele on rates of cognitive decline and brain atrophy during MCI and dementia stages of AD.
methodsA segmented linear mixed model was chosen for longitudinal modeling of cognitive and brain volumetric data of 73 ɛ3/ɛ3, 99 ɛ3/ɛ4, and 39 ɛ4/ɛ4 Alzheimer's Disease Neuroimaging Initiative participants who transitioned during the study from MCI to AD dementia.
resultsɛ4 carriers showed faster decline on MMSE, ADAS-11, CDR-SB, and MoCA scales, with the last two measures showing significant ɛ4 allele-dose effects after dementia transition but not during MCI. The ɛ4 effect was more prevalent in younger participants and in females. ɛ4 carriers also demonstrated faster rates of atrophy of the whole brain, the hippocampus, the entorhinal cortex, the middle temporal gyrus, and expansion of the ventricles after transitioning to dementia but not during MCI.
conclusionPossession of the ɛ4 allele is associated with a faster progression of dementia due to AD. Our observations support the notion that APOE genotype not only controls AD risk but also differentially regulates mechanisms of neurodegeneration underlying disease advancement. Furthermore, our findings carry significance for AD clinical trial design.
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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.