Abstract

Background: Advances in positron emission tomography 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) and dementia. Hypertension is believed to promote AD through arterial stiffening and cerebrovascular disease. We hypothesize that vascular measures are associated with amyloid in the brain. Methods: We studied 92 participants aged 83-96 in a follow-up of the Gingko Evaluation of Memory (GEM) Study with measures of: structural MRI of the brain; PiB-PET of brain amyloid deposition; resting blood pressure (BP), ankle brachial index (ABI) and mean arterial pressure (MAP); and vascular stiffness 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-4 genotyping, detailed neuropsychological battery and adjudication of cognition by committee. Participants with a diagnosis of dementia were excluded from the sub-study. Results: Half (44/92) non-demented older adults in this sub-study were PiB+ for amyloid deposition in the brain. Amyloid deposition was associated with ba PWV, systolic BP and MAP. After adjustment for covariates, one standard deviation increase in ba PWV resulted in a 2-fold increase in the odds of being PiB+. ApoE-4 status was not associated with PWV. Additionally, high white matter disease burden, but not total gray matter volume, was associated with increased cf PWV (p<0.01), hf PWV (p=0.03), SBP (p=0.05) and MAP (p=0.06). Conclusions: The adverse effects of hypertension and vascular stiffness on cerebral small vessel disease is one of the most important hypotheses as to the determinants of amyloid deposition and AD. This is the first report of a possible association between vascular stiffness, BP and in vivo amyloid deposition in non-demented individuals.

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