Vol 5 n° 3 - Anxiety II
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ultiple neurochemical pathways are involved in the pathology of Alzheimer’s disease (AD). The follow- ing factors have been implicated in the development of AD: b-amyloid; tau proteins; apolipoprotein E (APOE); degeneration of cholinergic, serotonergic, and dopamin- ergic neurons; oxidative damage; inflammation; estrogen deficiency; and glutamatergic neurotransmission. Neurochemical pathways for AD b-Amyloid It has been suggested that deposits of b-amyloid proteins appear to be the earliest morphological changes in the formation of neuritic plaques.1,2 These plaques ultimately lead to the death and destruction of surrounding axons and dendrites. Tau proteins Tau proteins are highly phosphorylated microtuble pro- teins that form neurofibrillary tangles. These abnormal filaments  form  either  parallel  bundles  or  randomly arranged paired helical filaments that extend to the den- dritic processes.2 These tangles lead to dysfunction and degeneration of nerve cells. Apolipoprotein E APOE is a cholesterol transport protein that has been linked to late-onset familial and sporadic AD.1-4 The gene for this protein is found on chromosome 19 and is inher- F r e e   p a p e r 2 9 9 Combination pharmacotherapy in Alzheimer’s disease Jacobo Mintzer, MD; Dena Armstrong, MD; Warachal E. Faison, MD M Keywords: Alzheimer’s disease; neurochemical pathway; combination therapy; donezepil; Gingko biloba; NSAID; memantine; adverse effect Author   affiliations:   Ralph   H.   Johnson   Veterans   Administration   Medical Center,  Charleston,  SC,  USA  (Jacobo  Mintzer);  Alzheimer’s  Research  and Clinical Programs, Medical University of South Carolina, Charleston, SC, USA (Jacobo Mintzer, Dena Armstrong, Warachal E. Faison) Address   for   correspondence:   Jacobo   Mintzer,   MD,   Ralph   H.   Johnson Veterans Administration Medical Center, Charleston, SC 29406, USA (e-mail: mintzerj@musc.edu) This   article   is   published   following   the   14th   Biological   Interface Conference held in Rouffach, France, between October 1 and 5, 2002, on the theme of “Drug Development.” Other articles from this meeting can be found in Dialogues in Clinical Neuroscience (2002, Vol 4, No 4). Alzheimer’s disease is a progressive, debilitating form of dementia affecting more than 18 million people worldwide. Without a cure, many patients and their families must turn to long-term care institutions during the later stages of the disease. Our current treatments only delay progression and help control behavioral symptoms. In recent years, research within this field has expanded to include many clinical trials on potential drug therapies. However, despite the numer- ous studies, the enigma of this disease remains. It is difficult, yet necessary, to stay abreast of emerging information that may warrant changes in current therapy. Rationale for com- bination therapy becomes evident as we review the multi- ple neurochemical pathways common to the disease. This paper will review available information on Alzheimer’s dis- ease pharmacotherapy, and evaluate data on the use of combination drug therapy. Individual efficacy, possible syn- ergistic effects, and the safety of combination therapy will also be addressed. © 2003, LLS SAS Dialogues Clin Neurosci. 2003;5:299-305. Copyright © 2003 LLS SAS.  All rights reserved www.dialogues-cns.org