Haemodynamic impairment along the Alzheimer’s disease continuum

Marina Diomedi, Alessandro Rocco, Chiara Giuseppina Bonomi, Alfredo Paolo Mascolo, Vincenzo De Lucia, Federico Marrama, Fabrizio Sallustio, Giacomo Koch, Alessandro Martorana

Research output: Contribution to journalArticlepeer-review


Background and purpose: Alzheimer's disease (AD) is considered a clinical and biological continuum identified via cerebrospinal fluid (CSF) or imaging biomarkers. Chronic hypoperfusion is held as one of the main features of Alzheimer's disease, as part of the processes causing neuronal degeneration. The mechanism responsible for such condition is still debated, although recently a direct connection with amyloid peptides has been shown. Here the aim was to investigate whether measures of hypoperfusion change along the AD continuum. Methods: Seventy patients with mild AD were recruited and stratified according to their CSF biomarker profile—as indicated by the National Institute on Aging and Alzheimer’s Association research framework—into patients with either isolated amyloid pathology (A+T−) or full-blown AD (A+T+), and further layered according to apolipoprotein E genotype. After evaluation of vascular risk factors, a transcranial Doppler was performed on each patient, to evaluate mean flow velocity and pulsatility index in the middle cerebral artery, and to calculate the breath-holding index. Patients were compared to a cohort of 17 healthy controls. Results: The breath-holding index was reduced in the AD continuum and was inversely correlated to CSF amyloid β42 levels. Such correlation was stronger in the A+T+ than in the A+T− group, and unexpectedly reached statistical significance only in the E3 and not in the E4 genotype carriers. Conclusions: These results suggest a tight and effective relationship between amyloid β42, vascular hypoperfusion, cerebrovascular reactivity and epsilon genotype.

Original languageEnglish
JournalEuropean Journal of Neurology
Publication statusAccepted/In press - 2021


  • Alzheimer's disease
  • Aβ42
  • BHI
  • CSF
  • epsilon genotype
  • vascular reactivity

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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