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Pulse wave velocity is associated with β-amyloid deposition in the brains of very elderly adults

TLDR
Arterial stiffness was highest in individuals with both high Aβ deposition and WMH, which has been suggested to be a “double hit” contributing to the development of symptomatic dementia.
Abstract
Objective: To determine arterial stiffness and β-amyloid (Aβ) deposition in the brain of dementia-free older adults. Methods: We studied a cohort of 91 dementia-free participants aged 83–96 years. In 2009, participants completed brain MRI and PET imaging using Pittsburgh compound B (PiB; a marker of amyloid plaques in human brain). In 2011, we measured resting blood pressure (BP), mean arterial pressure (MAP), and arterial stiffness by pulse wave velocity (PWV) in the central, peripheral, and mixed (e.g., brachial ankle PWV [baPWV]) vascular beds, using a noninvasive and automated waveform analyzer. Results: A total of 44/91 subjects were Aβ-positive on PET scan. Aβ deposition was associated with mixed PWV, systolic BP, and MAP. One SD increase in baPWV resulted in a 2-fold increase in the odds of being Aβ-positive ( p = 0.007). High white matter hyperintensity (WMH) burden was associated with increased central PWV, systolic BP, and MAP. Compared to Aβ-negative individuals with low WMH burden, each SD increase in PWV was associated with a 2-fold to 4-fold increase in the odds of being Aβ-positive and having high WMH. Conclusions: Arterial stiffness was associated with Aβ plaque deposition in the brain, independent of BP and APOE e4 allele. The associations differed by type of brain abnormality and vascular bed measured (e.g., WMH with central stiffness and Aβ deposition and mixed stiffness). Arterial stiffness was highest in individuals with both high Aβ deposition and WMH, which has been suggested to be a “double hit” contributing to the development of symptomatic dementia.

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Impairment of paravascular clearance pathways in the aging brain

TL;DR: Evaluating the efficiency of CSF–ISF exchange and interstitial solute clearance is impaired in the aging brain found that bulk flow drainage via the glymphatic system is driven by cerebrovascular pulsation, and is dependent on astroglial water channels that line paravascular CSF pathways.
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Impact of Hypertension on Cognitive Function: A Scientific Statement From the American Heart Association

TL;DR: Judicious treatment of hypertension, taking into account goals of care and individual characteristics (eg, age and comorbidities), seems justified to safeguard vascular health and, as a consequence, brain health.
Journal ArticleDOI

Impact of multiple pathologies on the threshold for clinically overt dementia

TL;DR: A clinical–pathological perspective on the role of multiple brain pathologies in dementia is provided followed by a review of the available clinical and biomarker data on some of the mixed pathologies.
Journal ArticleDOI

Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer's disease.

TL;DR: This work discusses glial dysfunction in AD with emphasis on neuronal and glial receptors that mediate Aβ-induced toxicity, and discusses other critical factors that may affect AD pathogenesis, including genetics, aging, variables related to environment, lifestyle habits, and APOE.
Journal ArticleDOI

Arterial stiffness, the brain and cognition: a systematic review.

TL;DR: Arterial stiffness is associated with cerebral small vessel disease and decreased cognitive function, however methodological limitations such as differing covariates between studies and an over-reliance on the MMSE to measure cognition are a concern across much of the literature.
References
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Journal ArticleDOI

Segmentation of brain MR images through a hidden Markov random field model and the expectation-maximization algorithm

TL;DR: The authors propose a novel hidden Markov random field (HMRF) model, which is a stochastic process generated by a MRF whose state sequence cannot be observed directly but which can be indirectly estimated through observations.
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Expert consensus document on arterial stiffness: methodological issues and clinical applications

TL;DR: This paper summarizes the proceedings of several meetings of the European Network for Non-invasive Investigation of Large Arteries and is aimed at providing an updated and practical overview of the most relevant methodological aspects and clinical applications in this area.
Journal Article

Expert consensus document on arterial stiffness : methodological issues and clinical applications. Commentary

TL;DR: In this paper, the authors summarized the proceedings of several meetings of the European Network for Non-invasive Investigation of Large Arteries and aimed at providing an updated and practical overview of the most relevant methodological aspects and clinical applications in this area.
Journal ArticleDOI

A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β.

TL;DR: An anatomically distinct clearing system in the brain that serves a lymphatic-like function is described and may have relevance for understanding or treating neurodegenerative diseases that involve the mis-accumulation of soluble proteins, such as amyloid β in Alzheimer's disease.
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Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: a prospective cohort study.

TL;DR: These projections suggest a prolonged preclinical phase of AD in which Aβ deposition reaches the authors' threshold of positivity at 17·0 (95% CI 14·9-19·9) years, hippocampal atrophy at 4·2 (3·6-5·1] years, and memory impairment at 3·3 (2·5-4·5) years before the onset of dementia (clinical dementia rating score 1).
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