Premium
S3–01–03: Technology in managing dementia
Author(s) -
Kaye Jeffrey A.
Publication year - 2007
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2007.04.010
Subject(s) - presentation (obstetrics) , dementia , emerging technologies , independence (probability theory) , disease , medicine , computer science , risk analysis (engineering) , process management , psychology , engineering , artificial intelligence , pathology , statistics , mathematics , radiology
neurovascular, and brain inflammation through the activity of the autonomic nervous system and modulation of brain parenchymal ACh. They may relieve ACh blockade of proinflammatory responses in regions distal from synaptic sites. Non-catalytic functions of cholinesterases (ChEs) include BuChE antagonism of AChE-S, and likely other pathological chaperone-mediated A fibrilization in a concentration-dependent manner. BuChE and AChE are also implicated in the metabolic syndrome, acute phase and neuro-immune responses, neuroepithelial and glial cell proliferation and activation, glutamate and oxidative homeostasis, and may have roles in preserving the integrity of myelin, perhaps via modulation of oligodendrocyte function. Objective(s): Elucidate the influence of ChEs and their inhibitors (ChE-Is) in neurodegeneration. Methods: Determine the effects of common polymorphisms of ChEs on risk, type and progression of dementia, and the effects of different ChE-Is that inhibit AChE and/or BuChE, and that markedly up-regulate AChE-R and/or AChE-S splice variants. Results: In Mild Cognitive Impairment (MCI) subjects, the BuChE K-variant may interact with risk factors for A deposition such as APOE e4 to accelerate A pathology. BuChE wt/wt may interact with risk factors for white matter demyelination such as APOE e4 and hyperhomocysteinemia to accelerate age-related loss of cognitive processing speed. In retrospective analyses of MCI trials, slowed progression of MCI to AD in APOE e4 carriers with less hippocampal volume loss has been seen for one ChE-I, and slowed progression of MCI to AD in wild-type BuChE (wt/wt) with less ventricular expansion was seen with another. Differential response to two ChE-Is by BuChE genotype was evidenced in a comparative 2-year study in younger ( 75 years) moderate AD patients. Conclusions: Polymorphisms, splice variant expression, and quantity of AChE and BuChE may effect risk of developing and progression of neurodegenerative disorders. More targeted interventions to modulate function and expression of ChEs may achieve improved symptomatic and disease modifying results that contrast with the generally modest overall treatment effects of currenty applied ChE-I therapy.