Arterial stiffness is associated with amyloid deposition in the brain independent of blood pressure

Abstract

Advances in PET imaging using amyloid specific ligands (e.g., PiB-PET) provide in vivo measurement of amyloid deposition in the brain, a hallmark of Alzheimer's disease (AD). One hypothesis for brain amyloid deposition is that it occurs in response to brain injury and inflammation secondary to cerebral small vessel disease (e.g., infarction and microhemorrhage). We hypothesize that arterial stiffness is associated with both white matter hyperintensities (WMH) and amyloid in the brain. We studied 92 non-demented participants aged 83–96 in a follow-up of the Gingko Evaluation of Memory (GEM) Study with measures of: brain MRI and PiB-PET; resting systolic blood pressure (SBP); diastolic blood pressure (DBP); pulse rate; and pulse wave velocity in the central (carotid-femoral (cf PWV) and heart femoral (hf PWV)), peripheral (femoral-ankle (fa PWV)), and mixed (brachial-ankle (ba PWV)) vascular beds, using a noninvasive and automated waveform analyzer (Colin Co., Komaki, Japan). Before study entry, all participants underwent APOE-ε4 genotyping, detailed neuropsychological battery and adjudication of cognition by committee (n=77 normal and n=15 MCI). Nearly half (44/92) of non-demented older adults in this sub-study were PiB+ for amyloid. Amyloid deposition was associated with ba PWV and SBP. After adjustment for covariates, one standard deviation increase in ba PWV resulted in nearly a 2-fold increase in the odds of being PiB+. Additional adjustment for APOE-ε4, mild cognitive impairment and SBP did not attenuate this association. Higher WMH volume was associated with increased central PWV (cf PWV (p<0.01) and hf PWV (p=0.03)) and SBP (p=0.05). Each standard deviation increase in ba PWV and cf PWV was associated with a 3 and 4-fold increase, respectively, in the odds of having both high amyloid and high WMH, relative to low amyloid and low WMH. This is the first study to show that PWV is associated with PiB-PET. Our results confirm initial reports showing associations between SBP and PiB-PET and extend this research by showing arterial stiffness is associated with in vivo amyloid deposition in non-demented individuals, independent of SBP and anti-hypertensive medication use. It will be important to determine if the prevention of elevated BP and vascular stiffness at middle-age will reduce amyloid deposition in the aging brain.