- © 2008 Canadian Medical Association or its licensors
Christopher Patterson and colleagues reviewed the modifiable risk factors for Alzheimer disease but did not mention that hypoxia may stimulate the development of this illness.1 Cigarette smoking, severe head injury with loss of consciousness and systolic hypertension in older people are risk factors that may cause hypoxia directly or induce it via neuronal ischemia; the disruption of neurovascular coupling has been implicated in hypertension,2 ischemic stroke and Alzheimer disease. We are interested in the authors' views on this issue as many patients with Alzheimer disease also have vascular infarctions3 and these patients deteriorate faster.4
Prolonged or chronic hypoxia has been shown to alter the excitability and functional expression of ion channels, which possibly contributes to neurodegeneration. Reduced oxygen levels result in the formation of β-amyloid protein through amyloidogenic processing of amyloid precursor protein, leading to upregulation of native L-type calcium channels and disruption of calcium homeostasis.5 Cholinergic neurons may be especially vulnerable to β-amyloid protein toxicity.6 The dysregulated calcium expression following hypoxia in central neurons may contribute to the neurotoxicity of β- amyloid protein and subsequent development of Alzheimer disease.
Patients with chronic obstructive pulmonary disease and obstructive sleep apnea syndrome often complain of memory lapses, which may result from intermittent or chronic hypoxic injury to the forebrain. Sun and colleagues defined the molecular mechanism of hypoxia leading to dementia and showed that hypoxia leads to increased β-secretase activity and production of β-amyloid protein.7 Until specific therapy becomes available, simple measures to prevent chronic hypoxic injury to the brain may help to prevent Alzheimer disease or may benefit people who already have the condition.
Footnotes
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Competing interests: None declared.
REFERENCES
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