Higher prevalence of cerebral white matter hyperintensities in homozygous APOE-ɛ4 allele carriers aged 45–75: Results from the ALFA study

Santiago Rojas, Anna Brugulat-Serrat, Nuria Bargalló, Carolina Minguillón, Alan Tucholka, Carles Falcon, Andreia Carvalho, Sebastian Morán, Manel Esteller, Nina Gramunt, Karine Fauria, Jordi Camí, José L. Molinuevo, Juan D. Gispert

    Research output: Contribution to journalArticleResearchpeer-review

    15 Citations (Scopus)

    Abstract

    © 2017, © The Author(s) 2017. 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.
    Original languageEnglish
    Pages (from-to)250-261
    JournalJournal of Cerebral Blood Flow and Metabolism
    Volume38
    Issue number2
    DOIs
    Publication statusPublished - 1 Feb 2018

    Keywords

    • Alzheimer’s disease
    • Apolipoprotein E
    • cerebrovascular
    • magnetic resonance imaging
    • risk factors
    • small vessel disease

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