Cholinesterase inhibitors (ChEIs), the mainstay treatment for dementia, have systemic actions that can affect cardiovascular and autonomic nervous system (ANS). Thirty-nine patients with Alzheimer s disease or mixed dementia underwent a comprehensive clinical evaluation, prior to and during ChEIs therapy, including orthostatic challenge, electrocardiogram (EKG) and heart rate variability (HRV) spectral analysis through Holter recordings. ChEIs therapy determined a decrease in supine diastolic blood pressure (BP) and in both diastolic and systolic BP in orthostatic position (79.8 +/- 9.0 vs. 76.4 +/- 9.3 mmHg, p=0.012; 79.9 +/- 11.6 vs. 75.3 +/- 9.9, p=0.005 and 144.6 +/- 25.8 vs. 137.6 +/- 21.1, p=0.020, respectively). Spectral analysis revealed no difference on static HRV components, but, during orthostatic challenge, an increase in LF/HF ratio (2.2+/-2.4 vs. 4.6+/-5.9, p=0.011) and a reduction in HF component emerged (1604.3 +/- 5610.1 vs. 266.1 +/- 525.5, p=0.010). ChEIs showed no influence on EKG parameters or on the occurrence of orthostatic hypotension. Treatment with ChEIs was associated with functional improvement of the ANS behavior and to a decrease in supine DBP and in both orthostatic SBP and DBP.