ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2018
Higher prevalence of cerebral white matter hyperintensities in homozygous APOE-ɛ4 allele carriers aged 45-75: Results from the ALFA study.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 2 of them syntheses that pooled it.
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Who cites it
36 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Global ethnic disparities in cerebral small vessel disease imaging markers and vascular risk factors: a systematic review and meta-analysis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Pooled it
- Apolipoprotein E Genotype Moderation of the Association Between Physical Activity and Brain Health. A Systematic Review and Meta-Analysis.Frontiers in aging neuroscience · 2021Pooled it
- Impact of APOE ε4 Genotype Load on Cognitive Function and Lipid Metabolism in Patients With Cerebral Small Vessel Disease.Annals of clinical and translational neurology · 2026Article
- APOE ε2 is associated with reduced risk of early post-stroke cognitive impairment but not with long-term functional outcome.BMC neurology · 2025Article
- The influence of socioeconomic factors and apolipoprotein ε genotype on cognitive outcomes in a multi-ethnic sample living with HCV and HIV.International journal of STD & AIDS · 2025Article
- Biological sex influences relationships between cerebral pulsatility and white matter hyperintensities in aging adults.American journal of physiology. Heart and circulatory physiology · 2025Article
- Regional cerebral blood flow reflects both neurodegeneration and microvascular integrity across the Alzheimer's continuum.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Polygenic risk for white matter hyperintensities is associated with early cerebrovascular events partly through hemodynamic measures in cognitively unimpaired middle-aged and older adults with low cardiovascular risk.Frontiers in neurology · 2025Article
- Two-Stage Recruitment Design to Reduce Magnetic Resonance Imaging Screening Cost for a Theoretical Clinical Trial of White Matter Hyperintensity Progression.Journal of the American Heart Association · 2024Article
- Sex-specific risk factors and clinical dementia outcomes for white matter hyperintensities in a large South Korean cohort.Alzheimer's research & therapy · 2024Observational
- A cell-autonomous role for border-associated macrophages in ApoE4 neurovascular dysfunction and susceptibility to white matter injury.Nature neuroscience · 2024Article
- Characterization of white matter hyperintensities in Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Cerebral microvascular changes in healthy carriers of the APOE-ɛ4 Alzheimer's disease risk gene.PNAS nexus · 2024Article
- Texture-based morphometry in relation to apolipoprotein ε4 genotype, ageing and sex in a midlife population.Human brain mapping · 2024Article
- Impact of age and apolipoprotein E ε4 status on regional white matter hyperintensity volume and cognition in healthy aging.Journal of the International Neuropsychological Society : JINS · 2024Article
- Genetic characterization of the ALFA study: Uncovering genetic profiles in the Alzheimer's continuum.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Alzheimer's disease genetic risk and changes in brain atrophy and white matter hyperintensities in cognitively unimpaired adults.Brain communications · 2024Article
- Cell autonomous role of border associated macrophages in ApoE4 neurovascular dysfunction and susceptibility to white matter injury.Research square · 2023Article
- LRP1 in vascular mural cells modulates cerebrovascular integrity and function in the presence of APOE4.JCI insight · 2023Article
- Role of white matter hyperintensity in effects of apolipoprotein E on cognitive injury.Frontiers in human neuroscience · 2023Review
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cerebral white matter hyperintensities are believed the consequence of small vessel disease and are associated with risk and progression of Alzheimer's disease. The ɛ4 allele of the APOE gene is the major factor accountable for Alzheimer's disease heritability. However, the relationship between white matter hyperintensities and APOE genotype in healthy subjects remains controversial. We investigated the association between APOE-ɛ4 and vascular risk factors with white matter hyperintensities, and explored their interactions, in a cohort of cognitively healthy adults (45-75 years). White matter hyperintensities were assessed with the Fazekas Scale from magnetic resonance images (575 participants: 74 APOE-ɛ4 homozygotes, 220 heterozygotes and 281 noncarriers) and classified into normal (Fazekas < 2) and pathological (≥2). Stepwise logistic regression was used to study the association between pathological Fazekas and APOE genotype after correcting for cardiovascular and sociodemographic factors. APOE-ɛ4 homozygotes, but not heterozygotes, bear a significantly higher risk (OR 3.432; 95% CI [1.297-9.082]; p = 0.013) of displaying pathological white matter hyperintensities. As expected, aging, hypertension and cardiovascular and dementia risk scales were also positively associated to pathological white matter hyperintensities, but these did not modulate the effect of APOE-ɛ4/ɛ4. In subjects at genetic risk of developing Alzheimer's disease, the control of modifiable risk factors of white matter hyperintensities is of particular relevance to reduce or delay dementia's onset.
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