Journal of Alzheimer's disease : JAD
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Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation and aggregation of amyloid-β peptide and loss of forebrain cholinergic neurons, resulting in progressive loss of memory and irreversible impairment of higher cognitive functions. Several studies have accounted for the close relationship between AD and the central cholinergic system, suggesting that a dysfunction of acetylcholine containing neurons in the brain contributes significantly to the cognitive deficit of individuals with AD. ⋯ The implications for anesthesia are also discussed. This knowledge could be valuable to improve anesthesia performance and patient safety.
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We first proposed the mitochondrial cascade hypothesis of sporadic Alzheimer's disease (AD) in 2004. Our core assumptions were a person's genes determine baseline mitochondrial function and durability, this durability determines how mitochondria change with advancing age, and critical changes in mitochondrial function initiate other pathologies characteristic of AD. Since then several lines of investigation report data consistent with or supportive of our hypothesis. ⋯ As predicted, AD therapies designed to reduce Abeta thus far have had at best very limited clinical benefits; our hypothesis identifies alternative therapeutic targets. While placing mitochondria at the apex of an AD cascade certainly remains controversial, it is increasingly accepted by the AD research community that mitochondria play an important role in the late-onset forms of the disease. Even if the mitochondrial cascade hypothesis proves incorrect, considering its assumptions could potentially advance our understanding of sporadic, late-onset AD.
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Review
Postoperative cognitive dysfunction: toward the Alzheimer's disease pathomechanism hypothesis.
Alzheimer's disease (AD), a chronic and progressive deterioration of memory and other cognitive domains, is the most common form of dementia. Because of related health and social impact, there is growing interest in assessing potential relationship between anesthesia and the onset and progression of chronic neurodegenerative disorders, including AD. ⋯ Preclinical studies are providing an increasing body of evidences on some of the mechanisms that link anesthetics to neuronal programmed cell death (apoptosis) and accumulation of misfolded proteins in the aging brain. Therefore, risk factors and pathomechanisms of chronic neurodegenerative disorders, including AD, and persistent postoperative-postanesthesia cognitive dysfunction may overlap.
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With a growing aging population, more patients suffering from dementia are expected to undergo surgery, thus being exposed to either general or regional anesthesia. This calls for specific attention ranging from the legal aspects of obtaining informed consent in demented patients to deciding on the use of premedication, choice of anesthetics, and management of postoperative pain. This review reflects on both general considerations concerning geriatric patients but also on the specific features of perioperatively used drugs and anesthetics that might have an impact on patients with Alzheimer's disease (AD).
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Both short and long term cognitive changes occur after cardiac surgery but the pathophysiology of these neurobehavioral changes remain incompletely understood. The cause of cognitive decline is most likely multifactorial and probably represents a complex interaction between cerebral microemboli, global cerebral hypoperfusion, inflammation, and genetic susceptibility. The problem of cognitive decline after cardiac surgery continues to increase as the surgical population becomes older and has more prevalent comorbid diseases. A better understanding of the etiology is essential to finding new preventive strategies as no definitive therapy exists for cognitive dysfunction.