Longitudinal changes in the control mechanisms for blood pressure and cerebral blood flow in Alzheimer's disease: Secondary results of a randomized controlled trial

Objective: Dynamic cerebral autoregulation (dCA) and baroreflex sensitivity (BRS) are key mechanisms involved in the homeostasis of blood pressure (BP) and cerebral blood flow. We assessed changes in these mechanisms in Alzheimer's disease (AD) during a 1.5 year follow-up. Methods: In this secondary analysis of a randomized controlled trial we measured beat-to-beat BP, heart rate, and cerebral blood flow velocity at baseline, 0.5 and 1.5 years, during: rest (spontaneous oscillations), repeated sit-stand maneuvers (induced oscillations), an orthostatic challenge, and hypo- and hypercapnia. dCA was estimated using transfer function analysis and the autoregulatory index on spontaneous and induced oscillations. BRS was estimated by calculating the heart rate response to BP changes during induced oscillations. Linear mixed models were used to assess changes over time. Results: 56 patients were included (mean age:73 ± 6 years, 57% female). BRS did not change over time. dCA parameters showed small changes after 0.5 years, suggestive of a reduction in efficiency (e.g. higher gain [linear mixed effect model: B = 0.09, SE = 0.03, P = 0.008] and lower phase [B = -9.7, SE= 3.2, P = 0.004] in the very low frequency domain, and lower autoregulatory index during induced oscillations [B = -0.69, SE = 0.26, P = 0.010]). These changes did not show further progression after 1.5 years of follow-up. Discussion: In this sample of patients with dementia due to AD we found no evidence that dCA or BRS become impaired during AD progression. This paves the way for further studies that investigate the safety and benefits of antihypertensive treatment in patients with AD.