APOE4 carriers display loss of anticipatory cerebral vascular regulation over AD progression

Figure 1.. Cerebral and peripheral vascular responses during orthostasis in APOE4 carriers and noncarriers with normal cognition. (A) Both genotypes experienced significant drops in middle cerebral artery blood flow velocity (MCAv) after standing. However, only APOE4 carriers showed an anticipatory increase in MCAv just before standing, while noncarriers did not show any significant change. (B) Anticipatory increases in beat-to-beat mean arterial pressure (MAP) and drops in MAP after standing were observed across all participants, regardless of genotype (C) APOE4 carriers demonstrated a greater anticipatory increase in MCAv but no difference MAP compared to noncarriers. (D) APOE4 carriers showed greater post-stand decreases in MCAv compared to noncarriers, but no difference in MAP decreases. (E) APOE4 carriers showed shorter MAP responses latencies (p=0.003) compared to noncarriers, while MCAv response latency was not different between genotypes (p=0.147) * indicates p<0.05 for between-group (genotype) differences.

Figure 2.. Cerebral vascular responses during orthostasis in over the course of AD progression in normal cognition (NC), mild cognitive impairment (MCI), and early-stage Alzheimer’s disease (AD). (A) Noncarriers of APOE4 showed no significant effect of diagnosis on MCAv. B) NC APOE4 carriers showed a significant anticipatory increase in MCAv, while this anticipatory response was attenuated in MCI and AD APOE4 carriers. (C) NC APOE4 carriers showed greater anticipatory percent increase in MCAv compared to noncarriers, but genotype differences were not observed in MCI and AD. (D) NC APOE4 carriers showed greater orthostatic-induced reduction in MCAv, but no genotype differences were observed in MCI and AD. (E) No genotype or diagnoses differences were observed for MCAv response latency during orthostasis. * indicates p<0.05 for between-diagnosis and between-genotype differences.

Figure 3.. Mean arterial blood pressure (MAP) responses during orthostasis in over the course of AD progression in normal cognition (NC), mild cognitive impairment (MCI), and early-stage Alzheimer’s disease (AD). (A) In noncarriers, MAP decreased at post-stand time points in response to orthostasis but showed no difference in anticipatory increase, regardless of diagnosis. B) In APOE4 carriers, there was an anticipatory increase in MAP only in NCs. (C) Anticipatory MAP, nor (D) orthostatic-induced change in MAP differed by diagnosis. (E) Shorter latency of orthostatic-induced MAP response observed in NC APOE4 carriers compared to noncarriers was also present at the MCI disease stage, but showed no difference in early AD. * indicates p<0.05 for between-diagnosis and between-genotype differences.