ReviewAlzheimer's disease and post-operative cognitive dysfunction
Introduction
Alzheimer's disease (AD) is one of the greatest public health problems in the US, and its impact will only increase with demographic changes anticipated in the coming decades. At current time, AD affects 4.5 million Americans and cost $100 billion a year on direct care alone. It is estimated that the number of AD patients will reach 13.2 millions in the United States of America by 2050, if no treatments for AD are found.
AD was first described in 1907 by professor Alois Alzheimer, a Bavarian psychiatrist with expertise in neuropathology (Alzheimer, 1907). Clinically, AD patients usually presents with subtle onset of memory loss followed by a slowly progressive dementia with a course of several years. Pathologically, AD patients have gross, diffuse atrophy of the cerebral cortex with secondary enlargement of the ventricular system, and there are neuritic plaques containing β-amyloid protein (Aβ), silver-staining neufibrillary tangles in neuronal cytoplasm, and accumulation of Aβ in arterial walls of cerebral blood vessels. Genetically, identification of several AD genes has provided a foundation for rapid progress in understanding the neuropathogenesis of AD. Numerous environmental factors, including aluminum, mercury, viruses, and prions, have been proposed as causes of AD. Recently, some perioperative factors like hypoxia, hypocapnia and anesthetics have been suggested to contribute to AD neuropathogenesis, and to cause post-operative cognitive dysfunction (POCD) through activating AD neuropathogenesis.
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Genetic etiology and their roles in AD neuropathogenesis
While the etiological underpinnings of AD are only partially understood, the inheritance of predisposing genetic factors appears to play a major role. After age, family history is the second greatest risk factor of AD. There is an emerging consensus that AD is complex and genetically heterogeneous disorder that is best explained by an age-dependent dichotomous model (Tanzi, 1999). Early-onset familial AD (EOFAD) mutations are rare, highly penetrant, and transmitted in an autosomal-dominant
Perioperative factors conceivably trigging AD neuropathogenesis
Earlier studies revealed that neurodegenerative disorders, such as AD and Parkinson's disease, might be accelerated by anesthesia and surgery (Bohnen et al., 1994a, Bohnen et al., 1994b, Muravchick and Smith, 1995). There have been numerous reports of delayed and long-lasting post-operative cognitive dysfunction following both cardiac and non-cardiac surgery [(Moller et al., 1998, Newman et al., 2001), reviewed in (Dodds and Allison, 1998)]. The recent international study of post-operative
Conclusion
AD, one of the most serious health problems in the US, is a progressive and insidious neurodegenerative disorder of the central nervous system characterized by global deficits in cognition ranging from loss of memory to impaired judgment and reasoning. Early studies revealed mutations in three genes (APP, PSEN1 and PSEN2) are responsible for up to 50% of early onset cases of FAD, whereas the APOE-ε4 gene variant is a risk factor of later onset AD. Recently, new genes such as α2M, IDE and UBQLIN1
Acknowledgements
This work was supported by the U.S. Public Health Service, AG 014713-07 (NIA), MH 60009-03 (NIMH), K12 (AG 00294-17), K08 (NS048140-01) and P60 (AG008812-15). We thank the Department of Anesthesia and Critical Care at Massachusetts General Hospital and Harvard Medical School for the support and help.
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