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Canadian Journal of Cardiology

Reply to Saka et al.—Rhythm Control and Dementia in Patients With Atrial Fibrillation: A Role for Glymphatic System?

Published:December 20, 2022DOI:https://doi.org/10.1016/j.cjca.2022.12.011
      To the Editor:
      We agree that additional mechanisms not described in our review contribute to the association between atrial fibrillation and cognitive decline. The authors propose that atrial fibrillation might reduce glymphatic clearance and thereby can lead to accumulation of amyloid-β, which subsequently might explain the higher risk of Alzheimer disease. While some studies suggest an impaired clearance of brain metabolites via the glymphatic system as a potential mechanism for white matter lesions,
      • Kress B.T.
      • Iliff J.J.
      • Xia M.
      • et al.
      Impairment of paravascular clearance pathways in the aging brain.
      it has to be emphasised that this concept has mainly been described in preclinical studies.
      • Iliff J.J.
      • Wang M.
      • Zeppenfeld D.M.
      • et al.
      Cerebral arterial pulsation drives paravascular CSF–interstitial fluid exchange in the murine brain.
      ,
      • Mestre H.
      • Tithof J.
      • Du T.
      • et al.
      Flow of cerebrospinal fluid is driven by arterial pulsations and is reduced in hypertension.
      Many more studies are needed to further elaborate this concept.

      Funding Sources

      The authors have no funding sources to declare.

      Disclosures

      Dr Blum reports research grants from the Swiss National Science Foundation, the Mach-Gaensslen Foundation, and the Gottfried and Julia Bangerter-Rhyner Foundation outside the submitted work. Dr Conen reports advisory board fees Roche Diagnostics and Trimedics and speaker fees from Servier and BMS/Pfizer.

      References

        • Kress B.T.
        • Iliff J.J.
        • Xia M.
        • et al.
        Impairment of paravascular clearance pathways in the aging brain.
        Ann Neurol. 2014; 76: 845-861
        • Iliff J.J.
        • Wang M.
        • Zeppenfeld D.M.
        • et al.
        Cerebral arterial pulsation drives paravascular CSF–interstitial fluid exchange in the murine brain.
        J Neurosci. 2013; 33: 18190-18199
        • Mestre H.
        • Tithof J.
        • Du T.
        • et al.
        Flow of cerebrospinal fluid is driven by arterial pulsations and is reduced in hypertension.
        Nat Commun. 2018; 9: 4878

      Linked Article

      • Mechanisms and Clinical Manifestations of Cognitive Decline in Atrial Fibrillation Patients: Potential Implications for Preventing Dementia
        Canadian Journal of CardiologyVol. 39Issue 2
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          Atrial fibrillation (AF) patients face an approximate 1.5-fold increased risk of cognitive decline compared with the general population. Among poststroke AF patients, the risk of cognitive decline is even higher with an estimated threefold increase. This article provides a narrative review on the current evidence and highlights gaps in knowledge and areas for future research. Although earlier studies hypothesized that the association between AF and cognitive decline is mainly a consequence of previous ischemic strokes, more recent evidence also suggests such an association in AF patients without a history of clinical stroke.
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      • Rhythm Control and Dementia in Patients With Atrial Fibrillation: A Role for Glymphatic System?
        Canadian Journal of CardiologyVol. 39Issue 2
        • Preview
          We welcome the review by Blum and Conen, which deals with critical connection between atrial fibrillation (AF) and cognitive impairment in an objective and instructive way.1 Indeed, AF-associated cognitive impairment (AFACI) is an underrecognised category of the dementia spectrum that is potentially targetable for prevention and treatment. Asymptomatic and symptomatic macro– and micro–cerebral embolism is the first to be proposed for AFACI mechanism. Cerebral hypoperfusion due to tachycardia and heart failure, impaired cerebral hemodynamic regulation during irregular cardiac cycles, and neuroendocrine and inflammatory perturbations also may play a role.
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