Hemodynamic impairment along the Alzheimer's Disease continuum.

BACKGROUND 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, though recently a direct connection with amyloid peptides has been shown. Here we aimed at investigating whether measures of hypoperfusion change along the AD continuum. METHODS 70 patients with mild AD were recruited and stratified according to their CSF biomarkers profile - as indicated by the NIA-AA research framework - into patients with either isolated amyloid pathology (A+T-) or full-blown AD (A+T+), and further layered according to ApoE genotype. After evaluation of vascular risk factors, we performed a Trans Cranial Doppler (TCD) on each patient, to evaluate mean flow velocity and pulsatility index in the middle cerebral artery, and to calculate the breath holding index (BHI). Patients were compared to a cohort of 17 healthy controls. RESULTS The BHI was reduced in the AD continuum and resulted inversely correlated to CSF Aβ42 levels. Such correlation was stronger in the A+T+ than in 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 Aβ42, vascular hypoperfusion, cerebrovascular reactivity and epsilon genotype.