Pulse pressure and systolic blood pressure associated with hippocampal volume by apolipoprotein (APO) carriers and Alzheimer disease status: Alzheimer’s disease neuroimaging initiative (ADNI) study

Abstract

It is increasingly evident that high blood pressure (BP) levels may be associated with brain volume reduction. A few studies have shown that high BP levels are associated with global and regional brain volume reduction with preferential localization in hippocampus and prefrontal cortex. We examined the relationship of blood pressure to hippocampal volume (HV) by Apolipoprotein (APO) carrier status from the Alzheimer's Disease Neuroimaging Initiative (ADNI) data. ADNI data in this analysis was downloaded on October 12, 2012. 1308 subjects were isolated: Alzheimer's disease (AD = 237), late mild cognitive impairment (LMCI = 454), early mild cognitive impairment (EMCI = 254) and control group (CN = 365). Subjects were reexamined at 6, 12, and 24 months, with 460 remaining at the last exam. Univariate analysis was conducted to examine data distribution and validate assumption for normality. Proc Mixed Effects Model was used to elucidate the relationships of HV to BP according to APO ε4 carriers and AD status while accounting for the effects of education, gender, history of hypertension, ethnicity and body mass index. Baseline characteristics of participants by AD status showed a mean age of 74.6±7.9 (AD); 73.3±7.5 (LMCI); 70.8±7.2 (EMCI) and 74.4±5.6 (CN). Females ranged from 39.4% – 49.6% by AD status. As anticipated AD subjects had lower HV: 5726.54±1003.26 (AD), 6491.91±1107.01 (LMCI), 7308.37±1027.11 (EMCI), 7361.12±920.69 (CN). Increased diastolic blood pressure was significantly associated with decreased HV among the controls who were non-APO ε4 carrier (β = -9.40, SE = 3.51, p = 0.008). EMCI non-APO ε4 carriers with high diastolic blood pressure had significantly higher HV (β = 17.10, SE = 7.94, p = 0.03). Increasing pulse pressure (PP) was positively associated with HV (p = 0.002) in EMCI non-APO ε4 carriers. In these ADNI data, a statistically significant association of diastolic BP and PP was observed with HV in non-APO ε4 carriers with EMCI, suggesting a possible role for elevated BP and PP in amyloid mediated early cognitive decline. This observation supports the view that CVD risk may promote amyloid-mediated early cognitive decline. This hypothesis should be examined in other studies.