Background: Epidemiological studies suggest an association between cardiovascular disease risk factors in
mid-life and Alzheimer’s disease (AD) in late-life. In the present study we used Pittsburgh Compound-B (PiB)
positron emission tomography (PET) to examine the relationship between blood pressure (BP) measures and this
brain imaging measurement of pre-symptomatic AD in a cohort of cognitively normal, late middle-aged APOE ε4
homozygotes (HM), heterozygotes (HT) and non-carriers (NC).
Methods: Mean systolic and diastolic BP was computed from three supine measurements. SPM5 was used
to characterize relationships between systolic BP (SBP), diastolic BP (DBP) and peripheral pulse pressure (PP)
with regional-to-cerebellar PiB PET distribution volume ratios (DVR) in 32 cognitively normal persons (mean age
65.5±4.5), including 8 HM, 11 HT, and 13 NC.
Results: The APOE ε4 groups did not differ significantly in demographic characteristics, clinical ratings or
neuropsychological test scores. 19% of the participants’ BP measurements met criteria for hypertension and
34% reported using anti-hypertensive medications. SBP was positively correlated and DBP negatively correlated
with PiB DVR bilaterally in frontal, temporal and precuneus regions (p<0.005-0.05, uncorrected). Higher PP was
associated with increased PiB DVR bilaterally in frontal and posterior cingulate-precuneus regions (p<0.005-0.05,
uncorrected). Controlling for APOE ε4 did not significantly alter these findings. The PP PiB DVR correlations
were significantly greater than the SBP or DBP correlations. Restricting the PP analysis to only normotensive
individuals who did not report using anti-hypertensive medications, higher PP was associated with increased
PiB DVR bilaterally in frontal, posterior cingulate, precuneus and medial temporal brain regions (p<0.005-0.05,
uncorrected), with no correlations in the opposite direction.
Conclusions: These findings provide additional evidence that increases in pulse pressure in mid-life may be
associated with increased risk of AD pathology. This study provides a rationale for using brain imaging to rapidly
evaluate the efficacy of anti-hypertensive medications for the pre-symptomatic treatment of AD.