Importance Recent studies show that cerebral β-amyloid (Aβ) deposition is associated with blood pressure and measures of arterial stiffness in nondemented individuals.
Objective To examine the association between measures of arterial stiffness and change in Aβ deposition over time.
Design, Setting, and Participants Deposition of Aβ was determined in a longitudinal observational study of aging by positron emission tomography using the Pittsburgh compound B twice 2 years apart in 81 nondemented individuals 83 years and older. Arterial stiffness was measured with a noninvasive and automated waveform analyzer at the time closest to the second positron emission tomography scan. All measures were performed under standardized conditions. Pulse wave velocity (PWV) was measured in the central (carotid-femoral and heart-femoral PWV), peripheral (femoral-ankle PWV), and mixed (brachial-ankle PWV) vascular beds.
Main Outcomes and Measures The change in Aβ deposition over 2 years was calculated from the 81 individuals with repeat Aβ–positron emission tomography.
Results The proportion of Aβ-positive individuals increased from 48% at baseline to 75% at follow-up. Brachial-ankle PWV was significantly higher among Aβ-positive participants at baseline and follow-up. Femoral-ankle PWV was only higher among Aβ-positive participants at follow-up. Measures of central stiffness and blood pressure were not associated with Aβ status at baseline or follow-up, but central stiffness was associated with a change in Aβ deposition over time. Each standard deviation increase in central stiffness (carotid-femoral PWV, P = .001; heart-femoral PWV,P = .004) was linked with increases in Aβ deposition over 2 years.
Conclusions and Relevance This study showed that Aβ deposition increases with age in nondemented individuals and that arterial stiffness is strongly associated with the progressive deposition of Aβ in the brain, especially in this age group. The association between Aβ deposition changes over time and generalized arterial stiffness indicated a relationship between the severity of subclinical vascular disease and progressive cerebral Aβ deposition.
Hypertension is linked to cognitive impairment and the pathologic features of Alzheimer disease (AD), including neurofibrillary tangles and β-amyloid (Aβ) plaques,1 as well as cerebrovascular disease and white matter hyperintensities (WMHs) in the brain.2 Arterial stiffness appears to play a major role in the relationship between hypertension and its consequences in the brain. Mounting evidence implicates arterial stiffness in the pathogenesis of brain aging,3 cerebrovascular disease,3impaired cognitive function, and dementia in the elderly.4
Recent studies using radiolabeled Aβ ligands (eg, Pittsburgh compound B) in positron emission tomography (PET) imaging demonstrated that more than half of nondemented adults older than 80 years have significant fibrillar Aβ deposition.5 With the exception of the apolipoprotein E4 (ApoE4) genotype and aging, the risk factors and determinants of Aβ deposition in the brain are poorly understood. Recent studies report that brain Aβ deposition is associated with blood pressure6,7and that arterial stiffness may play a central role. We recently showed that greater arterial stiffness (measured as higher pulse wave velocities [PWVs]) was associated with the amount of Aβ deposition in the brain.8 Interestingly, this association was independent of standard covariates and systolic blood pressure. However, it is unknown if arterial stiffness or other modifiable vascular factors are associated with the accumulation of Aβ deposition in the brain over time.
In this study, we evaluated the relationship between arterial stiffness and change in Aβ deposition, measured twice, 2 years apart, in a longitudinal observational study of nondemented older adults. We hypothesized that greater systemic arterial stiffness would be associated with the extent of Aβ accumulation in the brain during 2 years of follow-up.
JAMA Neurology 2014
Importance Recent studies show that cerebral β-amyloid (Aβ) deposition is associated with blood pressure and measures of arterial stiffness in nondemented individuals.
Objective To examine the association between measures of arterial stiffness and change in Aβ deposition over time.
Design, Setting, and Participants Deposition of Aβ was determined in a longitudinal observational study of aging by positron emission tomography using the Pittsburgh compound B twice 2 years apart in 81 nondemented individuals 83 years and older. Arterial stiffness was measured with a noninvasive and automated waveform analyzer at the time closest to the second positron emission tomography scan. All measures were performed under standardized conditions. Pulse wave velocity (PWV) was measured in the central (carotid-femoral and heart-femoral PWV), peripheral (femoral-ankle PWV), and mixed (brachial-ankle PWV) vascular beds.
Main Outcomes and Measures The change in Aβ deposition over 2 years was calculated from the 81 individuals with repeat Aβ–positron emission tomography.
Results The proportion of Aβ-positive individuals increased from 48% at baseline to 75% at follow-up. Brachial-ankle PWV was significantly higher among Aβ-positive participants at baseline and follow-up. Femoral-ankle PWV was only higher among Aβ-positive participants at follow-up. Measures of central stiffness and blood pressure were not associated with Aβ status at baseline or follow-up, but central stiffness was associated with a change in Aβ deposition over time. Each standard deviation increase in central stiffness (carotid-femoral PWV, P = .001; heart-femoral PWV,P = .004) was linked with increases in Aβ deposition over 2 years.
Conclusions and Relevance This study showed that Aβ deposition increases with age in nondemented individuals and that arterial stiffness is strongly associated with the progressive deposition of Aβ in the brain, especially in this age group. The association between Aβ deposition changes over time and generalized arterial stiffness indicated a relationship between the severity of subclinical vascular disease and progressive cerebral Aβ deposition.
Hypertension is linked to cognitive impairment and the pathologic features of Alzheimer disease (AD), including neurofibrillary tangles and β-amyloid (Aβ) plaques,1 as well as cerebrovascular disease and white matter hyperintensities (WMHs) in the brain.2 Arterial stiffness appears to play a major role in the relationship between hypertension and its consequences in the brain. Mounting evidence implicates arterial stiffness in the pathogenesis of brain aging,3 cerebrovascular disease,3impaired cognitive function, and dementia in the elderly.4
Recent studies using radiolabeled Aβ ligands (eg, Pittsburgh compound B) in positron emission tomography (PET) imaging demonstrated that more than half of nondemented adults older than 80 years have significant fibrillar Aβ deposition.5 With the exception of the apolipoprotein E4 (ApoE4) genotype and aging, the risk factors and determinants of Aβ deposition in the brain are poorly understood. Recent studies report that brain Aβ deposition is associated with blood pressure6,7and that arterial stiffness may play a central role. We recently showed that greater arterial stiffness (measured as higher pulse wave velocities [PWVs]) was associated with the amount of Aβ deposition in the brain.8 Interestingly, this association was independent of standard covariates and systolic blood pressure. However, it is unknown if arterial stiffness or other modifiable vascular factors are associated with the accumulation of Aβ deposition in the brain over time.
In this study, we evaluated the relationship between arterial stiffness and change in Aβ deposition, measured twice, 2 years apart, in a longitudinal observational study of nondemented older adults. We hypothesized that greater systemic arterial stiffness would be associated with the extent of Aβ accumulation in the brain during 2 years of follow-up.
JAMA Neurology 2014
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