“Boomerang Neuropathology-of Late-Onset Alzheimer’s Disease is Shrouded in Harmful “BDDS- Breathing, Diet, Drinking, and Sleep During Aging

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• 作者：Mak Adam Daulatzai
• 关键词：Alzheimer’s disease ; Obstructive sleep apnea ; Unhealthy diet ; Excess alcohol consumption ; Sleep restriction ; Neuroinflammation ; Epigenetics
• 刊名：Neurotoxicity Research
• 出版年：2015
• 出版时间：July 2015
• 年：2015
• 卷：28
• 期：1
• 页码：55-93
• 全文大小：1,179 KB
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• 作者单位：Mak Adam Daulatzai (1)
  
  1. Sleep Disorders Group, EEE Department, Melbourne School of Engineering, The University of Melbourne, 3rd Floor, Room No. 344, Parkville, VIC, 3010, Australia
  
• 刊物主题：Neurosciences; Neurology; Neurochemistry; Pharmacology/Toxicology; Neurobiology; Cell Biology;
• 出版者：Springer US
• ISSN：1476-3524

文摘

Brain damage begins years before substantial neurodegeneration and Alzheimer’s dementia. Crucial fundamental activities of life are breathing, eating, drinking, and sleeping. When these pivotal functions are maligned over a prolonged period, they impart escalating dyshomeostasis. The latter may lead to disastrous consequences including cognitive dysfunction and Alzheimer’s disease (AD). The current theme here is that multiple pathophysiological derangements are promoted over a prolonged period by the very fundamental activities of life—when “rendered unhealthy.-They may converge on several regulating/modulating factors (e.g., mitochondrial energy production, oxidative stress, innate immunity, and vascular function) and promote insidious neuropathology that culminates in cognitive decline in the aged. This is of course associated with the accumulation of amyloid beta and phosphorylated tau in the brain. Epidemiological, biomarker, and neuroimaging studies have provided significant copious evidence on the presence of indolent prodromal AD neuropathology many years prior to symptomatic onset. Progressive oxidative damage to specific gene promoters may result in gene silencing. A mechanistic link may possibly exist between epigenomic state, DNA damage, and chronically unhealthy/dysfunctional body systems. This paper, therefore, addresses and delineates the deleterious pathophysiological impact triggered by dysfunctional breathing, harmful diet, excess of alcohol consumption, and sleep deprivation; indeed, their impact may alter epigenetic state. It is mandatory, therefore, to abrogate cognitive decline and attenuate AD pathology through adoption of a healthy lifestyle, in conjunction with combination therapy with known moderators of cognitive decline. This strategy may thwart multiple concurrent and synergistic pathologies, including epigenetic dysfunction. A multi-factorial therapeutic intervention is required to overcome wide ranging neuropathology and multi-faceted disease process. Such an approach may attenuate neuropathology and ameliorate memory dysfunction.