170 research outputs found
Is the incidence of dementia declining?
No full textAction on preventative health could lower the risk of dementia for future generations, argues this report.
Executive summary
The world-wide projections of the prevalence of dementia in the coming decades have been a source of great concern to health systems and societies around the world. The World Alzheimer Report 2010 estimated that there were 36 million people with dementia in 2010, with an expected doubling every 20 years to nearly 115 million in 2050. These sobering figures are based on assumptions that the age-adjusted prevalence of dementia would remain constant and the population would continue to age at the current rate.
The assumption that the incidence of dementia will remain stable is now being put into question. There is emerging evidence to suggest that the incidence of dementia in older individuals may be declining. It appears that this change may be recent and has possibly occurred only in the last one to two decades. It may also be restricted so far to high income countries, although data from low and middle income countries are lacking.
The reasons for this change are not understood, but education, more stimulating environments and better control of vascular risk factors may have contributed. The data are still preliminary and more studies are needed to establish the extent of this change and understand its causes. It should be noted that the decline is not large enough to offset the increase in prevalence of dementia due to the ageing of the population and therefore investment and efforts to develop better treatments and care for people with dementia need to continue.
The fact that dementia rates are malleable is an encouraging finding but the reduction cannot be taken for granted as gains in population health can easily be lost if societies do not remain vigilant and continually proactive. These preliminary findings provide a strong argument for large scale Government investment in dementia-prevention strategies, which should start from early life
Sachdev–Ye–Kitaev model as Liouville quantum mechanics
No full textAbstractWe show that the proper inclusion of soft reparameterization modes in the Sachdev–Ye–Kitaev model of N randomly interacting Majorana fermions reduces its long-time behavior to that of Liouville quantum mechanics. As a result, all zero temperature correlation functions decay with the universal exponent ∝τ−3/2 for times larger than the inverse single particle level spacing τ≫NlnN. In the particular case of the single particle Green function this behavior is manifestation of the zero-bias anomaly, or scaling in energy as ϵ1/2. We also present exact diagonalization study supporting our conclusions
The Toll of Vascular Insufficiency: Implications for the Management of Peripheral Arterial Disease
No full textPeripheral artery disease (PAD) can result in limb loss within six months of diagnosis in a subset of patients who cannot undergo endovascular or surgical revascularization yet continues to maintain a marginal position in cardiovascular research. While a body of literature continues to grow describing the role of danger signaling and innate immunity in cardiac biology, the role of these pathways in the ischemic myopathy associated with PAD has not been extensively studied. The following report will review the current literature on the role of Toll-like receptor (TLR) signaling in cardiovascular biology as well as in nonischemic myopathy. While attenuation of TLR signaling has not been shown to be clinically useful in the treatment of infectious inflammation, it may show promise in the management of severe arterial insufficiency
Perpetual change: autophagy, the endothelium, and response to vascular injury
No full textAbstract
Current studies of vascular health, aging, and autophagy emphasize how the endothelium adapts to stress and contributes to disease. The endothelium is far from an inert barrier to blood-borne cells, pathogens, and chemical signals; rather, it actively translates circulating mediators into tissue responses, changing rapidly in response to physiologic stressors. Macroautophagy—the cellular ingestion of effete organelles and protein aggregates to provide anabolic substrates to fuel bioenergetics in times of stress—plays an important role in endothelial cell homeostasis, vascular remodeling, and disease. These roles include regulating vascular tone, sustaining or limiting cell survival, and contributing to the development of atherosclerosis secondary to infection, inflammation, and angiogenesis. Autophagy modulates these critical functions of the endothelium in a dynamic and perpetual response to tissue and intravascular cues.</jats:p
HMGB1 and TLR4 mediate skeletal muscle recovery in a murine model of hindlimb ischemia
No full textBackgroundWe have previously shown that the danger signal high-mobility group box 1 (HMGB1) promotes angiogenesis when administered to ischemic muscle. HMGB1 signals through Toll-like receptor 4 (TLR4) as well as the receptor for advanced glycation end-products (RAGE). However, the actions of these receptors in ischemic injury and muscle recovery are not known. We hypothesize that TLR4 mediates tissue recovery and angiogenesis in response to ischemia.MethodsFemoral artery ligation was performed in control, TLR4 competent (C3H/HeOuJ) and incompetent (C3H/HeJ) mice, as well as RAGE knockout mice and their C57B6 control counterparts. In other experiments, control mice were pretreated with anti-HMGB1 neutralizing antibody before femoral artery ligation. After 2 weeks, limb perfusion was evaluated using laser Doppler perfusion imaging and reported as the ratio of blood flow in the ischemic to nonischemic limb. Muscle necrosis, fat replacement, and vascular density in the anterior tibialis muscle were quantified histologically. In vitro, TLR4 and RAGE expression was evaluated in human dermal microvascular endothelial cells in response to hypoxia. Human dermal microvascular endothelial cells treated with HMGB1 alone and in the presence of anti-TLR4 antibody were probed for phosphorylated extracellular signal-regulated kinase (ERK), a signaling molecule critical to endothelial cell (EC) angiogenic behavior.ResultsBoth anti-HMGB1 antibody as well as defective TLR4 signaling in HeJ mice resulted in prominent muscle necrosis 2 weeks after femoral artery ligation. Control HeOuJ mice had less necrosis than TLR4 incompetent HeJ mice, but a greater amount of fat replacement. In contrast to control C3H mice, control C57B6 mice demonstrated prominent muscle regeneration with very little necrosis. Muscle regeneration was not dependent on RAGE. While vascular density did not differ between strains, mice with intact RAGE and TLR4 signaling had less blood flow in ischemic limbs compared with mutant strains. In vitro, EC TLR4 expression increased in response to hypoxia while TLR4 antagonism decreased HMGB1-induced activation of extracellular signal-regulated kinase.ConclusionsBoth HMGB1 and TLR4 protect against muscle necrosis after hindlimb ischemia. However, muscle regeneration does not appear to be tied to vascular density. HMGB1 likely activates angiogenic behavior in ECs in vitro, and this activation may be modulated by TLR4. The improvement in blood flow seen in mice with absent TLR4 and RAGE signaling may suggest anti-angiogenic roles for both receptors, or vasoconstriction induced by TLR4 and RAGE mediated inflammatory pathways.Clinical RelevanceNonreconstructable peripheral artery disease causes significant functional disability and is associated with a high risk of limb loss. The mechanisms that govern muscle recovery and angiogenesis after ischemia are important to understand to improve medical therapy for patients who cannot have an intervention. This article evaluates the role of high-mobility group box 1 and the innate immune receptor Toll-like receptor 4 in mediating muscle recovery after ischemia. While high-mobility group box 1 has been shown to mediate end-organ damage in other clinical scenarios, it may also play an important role in regenerative processes such as myocyte regeneration and angiogenesis
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