Transient cerebral hypoperfusion and hypertensive events during atrial fibrillation: a plausible mechanism for cognitive impairment

Abstract

Atrial fibrillation (AF) is associated with an increased risk of dementia and cognitive decline, independent of strokes. Several mechanisms have been proposed to explain this association, but altered cerebral blood flow dynamics during AF has been poorly investigated: in particular, it is unknown how AF influences hemodynamic parameters of the distal cerebral circulation, at the arteriolar and capillary level. Two coupled lumped-parameter models (systemic and cerebrovascular circulations, respectively) were here used to simulate sinus rhythm (SR) and AF. For each simulation 5000 cardiac cycles were analyzed and cerebral hemodynamic parameters were calculated. With respect to SR, AF triggered a higher variability of the cerebral hemodynamic variables which increases proceeding towards the distal circulation, reaching the maximum extent at the arteriolar and capillary levels. This variability led to critical cerebral hemodynamic events of excessive pressure or reduced blood flow: 303 hypoperfusions occurred at the arteriolar level, while 387 hypertensive events occurred at the capillary level during AF. By contrast, neither hypoperfusions nor hypertensive events occurred during SR. Thus, the impact of AF per se on cerebral hemodynamics candidates as a relevant mechanism into the genesis of AF-related cognitive impairment/dementia.

Figure 1. Schematic representation of the algorithm adopted to model SR and AF intervals in the cerebral dynamics.

Left box: RR series and probability density functions. Central box: representative series for the systemic arterial pressure, P_a, as modeled through the cardiovascular model. Right box: cerebral model dynamics, receiving P_a from the cardiovascular model as input. SR: blue curves, AF: red curves.

Figure 2. Scheme of the cerebral model.

R: resistance, C: compliance, Q: flow rate, P: pressure. The left ICA-MCA pathway is highlighted in orange. P_a: systemic arterial pressure; Q_ICA: internal carotid flow rate; Q_BA: basilar artery flow rate; P_BA,willis: basilar artery pressure at the entrance of the Circle of Willis; Q_ACA1: precommunicating anterior cerebral artery flow rate; Q_PCA1: precommunicating posterior cerebral artery flow rate; P_ACA: anterior cerebral artery pressure; P_MCA: middle cerebral artery pressure; P_ACA: posterior cerebral artery pressure; Q_ACA2: postcommunicating anterior cerebral artery flow rate; Q_PCA2: postcommunicating posterior cerebral artery flow rate; Q_MCA: middle cerebral artery flow rate; P_da: anterior distal pressure; P_dm: middle distal pressure; P_dp: posterior distal pressure; Q_da: anterior distal flow rate; Q_dm: middle distal flow rate; Q_dp: posterior distal flow rate; P_c: cerebral capillary pressure; Q_pv: proximal venous flow rate; Q_f: cerebrospinal flow rate at cerebral capillaries; P_ic: intracranial pressure; P_v: cerebral venous pressure; Q_vs: terminal intracranial venous flow rate; P_vs: dural sinus pressure; Q_o: cerebrospinal flow rate at the dural sinuses; Q_out: total outflow rate.

Figure 3. Examples of percentile, hypoperfusion and hypertensive event evaluation.

(a–b) Example of percentile evaluation in the case of P_dm,left (p(P_dm,left) is the probability density function). SR thresholds (5% SR and 95% SR, dashed lines) individuate the 5^th and 95^th percentiles in SR (panel a, blue areas), while they correspond to the 27^th and 91^st percentiles in AF (panel b, red areas). (c) Example of hypoperfusion lasting 2 beats (Q_dm,left). Average flow rate per beats are represented by green horizontal lines, while the 5th percentile SR threshold is displayed through the dashed blue horizontal line. (d) Example of hypertensive event lasting 3 beats (P_dm,left). Average pressure per beats are reported with black horizontal lines, while the dashed blue horizontal line represents the 95th percentile SR threshold.

Figure 4. Pathway ICA-MCA. Representative pressure and flow rate series are reported for the selected pathway during SR (blue) and AF (red).

Figure 5. Percentile evaluation.

Evaluation of AF percentiles corresponding to the SR thresholds (5% SR and 95% SR) along the ICA-MCA pathway: (a) Flow rate, 5% SR; (b) Flow rate, 95% SR; (c) Pressure, 5% SR; (d) Pressure, 95% SR.

Figure 6. Absolute frequency of hypoperfusions and hypertensive events during AF along the ICA-MCA pathway.

(a) Hypoperfusions; (b) hypertensive events. The abscissa indicates the number of consecutive beats characterizing the events.