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<p>The apolipoprotein E4 (APOE4) allele is the strongest genetic risk factor for Alzheimer’s disease (AD) and is linked to poorer cerebrovascular health. Cerebrovascular reactivity (CVR), an indicator of vascular reserve, and cerebral pulsatility (CP), a marker of vascular stiffness, are sensitive biomarkers of early vascular dysfunction associated with aging and AD. However, the relationship between APOE4 status and these cerebrovascular metrics remains unclear. This study investigated whether the APOE genotype influences longitudinal changes in CVR and CP, and their association with cognitive performance in cognitively unimpaired individuals. We utilized the PREVENT-AD cohort, including 101 APOE4 carriers (30 males and 71 females) and 152 non-APOE4 carriers (48 males and 104 females) aged 55 and older. Relative CVR and CP were derived from resting state functional magnetic resonance imaging data, with regional values extracted from cerebral arterial territories. Results indicated significant interactions between APOE4 status and relative CVR in the left middle cerebral artery and left posterior cerebral artery (PCA) territories. APOE4 status disaggregated analyses revealed that APOE4 carriers uniquely presented a significant decline in relative CVR within the left PCA. Furthermore, sex-specific effects were identified, with female APOE4 carriers having lower relative CVR in the right anterior cerebral artery territory compared to female non-carriers. Importantly, higher relative CVR was positively associated with better cognitive performance in APOE4 carriers. No significant effects of APOE4 status on CP were found. Together, these findings suggest that relative CVR may be an important early measure of cerebrovascular health and cognition in cognitively intact APOE4 carriers.</p>

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Longitudinal effects of cerebrovascular reactivity and cerebral pulsatility in cognitively intact older adults with APOE4: links with cognition

  • 期刊论文

  • 发表日期：

    2025年12月6日

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  • Zacharie Potvin-Jutras,
  • Pierre-Luc Tremblay,
  • Hanieh Mohammadi,
  • Sylvia Villeneuve,
  • R. Nathan Spreng,
  • Claudine J. Gauthier,
  • Sylvia Villeneuve,
  • Judes Poirier,
  • John C.S. Breitner,
  • Jennifer Tremblay-Mercier,
  • Jordana Remz,
  • Jean-Michel Raoult,
  • Yara Yakoub,
  • Jonathan Gallego-Rudolf,
  • Ting Qiu,
  • Alfonso Fajardo Valdez,
  • Bery Mohammediyan,
  • Mohammadali Javanray,
  • Amelie Metz,
  • Safa Sanami,
  • Valentin Ourry,
  • Alfie Wearn,
  • Alexandre Pastor-Bernier,
  • Manon Edde,
  • Julie Gonneaud,
  • Cherie Strikwerda-Brown,
  • Christine L. Tardif,
  • Claudine J. Gauthier,
  • Maxime Descoteaux,
  • Mahsa Dadar,
  • Étienne Vachon-Presseau,
  • Andrée-Ann Baril,
  • Simon Ducharme,
  • Maxime Montembeault,
  • Maiya R. Geddes,
  • Jean-Paul Soucy,
  • Natasha Rajah,
  • Robert Laforce,
  • Christian Bocti,
  • Christos Davatzikos,
  • Lune Bellec,
  • Pedro Rosa-Neto,
  • Sylvain Baillet,
  • Alan C. Evans,
  • D. Louis Collins,
  • M. Mallar Chakravarty,
  • Kaj Blennow,
  • Henrik Zetterberg,
  • R. Nathan Spreng,
  • Alexa Pichet Binette

摘要

The apolipoprotein E4 (APOE4) allele is the strongest genetic risk factor for Alzheimer’s disease (AD) and is linked to poorer cerebrovascular health. Cerebrovascular reactivity (CVR), an indicator of vascular reserve, and cerebral pulsatility (CP), a marker of vascular stiffness, are sensitive biomarkers of early vascular dysfunction associated with aging and AD. However, the relationship between APOE4 status and these cerebrovascular metrics remains unclear. This study investigated whether the APOE genotype influences longitudinal changes in CVR and CP, and their association with cognitive performance in cognitively unimpaired individuals. We utilized the PREVENT-AD cohort, including 101 APOE4 carriers (30 males and 71 females) and 152 non-APOE4 carriers (48 males and 104 females) aged 55 and older. Relative CVR and CP were derived from resting state functional magnetic resonance imaging data, with regional values extracted from cerebral arterial territories. Results indicated significant interactions between APOE4 status and relative CVR in the left middle cerebral artery and left posterior cerebral artery (PCA) territories. APOE4 status disaggregated analyses revealed that APOE4 carriers uniquely presented a significant decline in relative CVR within the left PCA. Furthermore, sex-specific effects were identified, with female APOE4 carriers having lower relative CVR in the right anterior cerebral artery territory compared to female non-carriers. Importantly, higher relative CVR was positively associated with better cognitive performance in APOE4 carriers. No significant effects of APOE4 status on CP were found. Together, these findings suggest that relative CVR may be an important early measure of cerebrovascular health and cognition in cognitively intact APOE4 carriers.