Amyloid burden and sleep blood pressure in amnestic mild cognitive impairment

Abstract

Objective: To determine whether cortical β-amyloid (Aβ) deposition is associated with circadian blood pressure (BP) profiles and dynamic cerebral blood flow (CBF) regulation in patients with amnestic mild cognitive impairment (aMCI).

Methods: Forty participants with aMCI were included in this study. Cortical Aβ depositions were measured by (18)F-florbetapir PET and expressed as the standardized uptake value ratio (SUVR) relative to the cerebellum. Circadian BP profiles were measured by 24-hour ambulatory monitoring during awake and sleep periods. The dipping status of sleep BP (i.e., the percent changes from the awake BP) was calculated and dichotomized into the dipper (≥10%) and nondipper (<10%) groups. Dynamic CBF regulation was assessed by a transfer function analysis between beat-to-beat changes in BP and CBF velocity measured from the middle cerebral artery during a repeated sit-stand maneuver.

Results: Age was positively correlated with a greater Aβ deposition in the posterior cingulate, precuneus, and mean cortex. Accounting for the age effect, attenuated reductions in sleep systolic BP were associated with higher levels of posterior cingulate SUVR. Consistently, the nondippers exhibited a higher SUVR in the posterior cingulate than the dippers. Transfer function gain between changes in BP and CBF velocity was diminished in the nondippers, and moreover those individuals with a lower gain exhibited a higher SUVR in the posterior cingulate.

Conclusions: Attenuated reductions in sleep BP are associated with a greater Aβ burden in the posterior cingulate and altered dynamic CBF regulation in patients with aMCI.

Figure 1. Amyloid burden with age and apolipoprotein E4 status

(A) 18F-florbetapir standardized uptake value ratio (SUVR) in relation to age. (B) Group comparisons of 18F-florbetapir SUVR between APOE4 carriers and noncarriers. All the APOE4 carriers were heterozygotes. APOE4 data were available from 35 participants. Horizontal thick lines represent group-averaged mean values.

Figure 2. Sleep systolic blood pressure and amyloid burden in the posterior cingulate cortex

(A) Circadian changes in ambulatory systolic blood pressure (SBP) from awake to sleep period. (B) Age-adjusted partial correlation between sleep SBP dip and posterior cingulate standardized uptake value ratio (SUVR). Standardized residuals of sleep SBP dip and posterior cingulate SUVR were calculated by regressing out the effect of age.

Figure 3. Amyloid burden in sleep systolic blood pressure dippers and nondippers

(A) Group-averaged maps of 18F-florbetapir standardized uptake value ratio (SUVR) in dippers and nondippers. (B) Age-adjusted group comparisons of 18F-florbetapir SUVR in the posterior cingulate, precuneus, and mean cortex. Standardized residual of ¹⁸F-florbetapir SUVR was calculated by regressing out the effect of age. Horizontal thick lines represent group-averaged mean values.

Figure 4. Transfer function metrics of the cerebral dynamic pressure-flow relation assessed during a repeated sit-stand maneuver

(A) Gain, (B) phase, (C) normalized gain, (D) coherence. Group-averaged waveforms were generated from dippers and nondippers. The center of the shade areas represents the sit-stand frequency (i.e., 0.05 Hz) where hemodynamic oscillations were induced.