Alzheimer’s disease therapy

Giacobini, E. (1998) Invited review cholinesterase inhibitors for Alzheimer s disease therapy from tacrine to future applications. Neuro chemistry International 32,413-419. 

Choudhary MI, Nawaz SA, Zaheer-ul-Haq Azim MK, cr 7/.,Juhflorine, A potent natural peripheral anionic-site-binding inhibitor of acetylchoflnesterase with calcium-channel blocking potential, a leading candidate for Alzheimer s disease therapy, Biochem Biophys Res Comm 332 1171—1179, 2005. 

Fahrenholz, F., and Postina, R. (2006). Alpha-secretase activation—an approach to Alzheimer s disease therapy. Neurodegener Dis 3, 255-261. 

Greig, N.H., Lahiri, D.K. and Sambamurti, K. (2002) Butyrylcholinesterase an important new target in Alzheimer s disease therapy. Int Psycho geriatr, 14 Suppl 1, 77-91. 

Piazzi, L, Rampa, A., Bisi, A., Gobbi, S., Belluti, R, Cavalli, A., Bartolini, M., Andrisano, V., Valenti, R, Recanatini, M. 3-(4-[[Benzyl (methyl)amino]methyl]phenyl)-6,7-dimethoxy-2H-2-chromenone (AP2238) inhibits both acetylcholinesterase and acetylcholinesterase-induced beta-amyloid aggregation a dual function lead for Alzheimer s disease therapy. J. Med. Chem. 2003,46,2279-2282. 

In recent years increasing attention has been paid to the possibility of delaying or even reversing the memory loss that accompanies old age or the more tragic loss of human capabilities associated with premature senility - Alzheimer s disease. Progress is hampered by the difficulty of identifying suitable animal tests, and there is presently no reliable therapy. 

Amyloid precursor protein (APP) is the precursor of (3-amyloid, the main component of senile plaques found in the brain of Alzheimer patients. The production of (3-amyloid from APP to the cells from abnormal proteolytic cleavage of the amyloid precursor protein. Enzymes involved in this cleavage may be suitable targets for the therapy of Alzheimer s disease. 

Care for people with dementia is demanding of resources, while the outcomes of care are uncertain. To date, the economic analyses of care strategies have been limited to new drug therapies for people with Alzheimer s disease. Full economic evaluations to compare both the costs and consequences have only been conducted for one of these dmgs, donepezil. However, problems with the design and data used in these studies mean that they do not provide robust evidence to determine appropriate management strategies for dementia. 

Winblad B (1999b). The cost-effectiveness of Donepezil therapy in Swedish patients with Alzheimer s disease a Markov model. Clin Therll, 1320-40. 

Stewart A, et al (1998). Pharmacotherapy for people with Alzheimer s disease a Markov-cycle evaluation of five years therapy using donepezil. Int J Geriatr Psychiatry 13, 445—53. 

Skovronsky, DM and Lee, VM-Y (2000) -secretase revealed starting gate for race to novel therapies for Alzheimer s disease. Trends Pharmacol. Sci. 21 161-163. 

Despite the indications for involvement of free radicals in Alzheimer s disease and Down s syndrome pathogenesis summarized above, more evidence is needed to establish a role for free-radical mechanisms in these disease processes. If free radicals can be demonstrated to play a role in the pathogenesis of Alzheimer s disease and Down s syndrome, then this would set the stage for chronic therapy with antioxidants in these disease states. 

Describe how nonpharmacologic therapy is combined with pharmacologic therapy for patients with Alzheimer s disease. 

Once a tolerated agent is found, continue that therapy until poor tolerance or compliance occurs, no clinical improvement is seen with 3 to 6 months of optimal dosing, or the pretreatment deterioration rate continues. Inform the patient and the caregiver that the treatments available for Alzheimer s disease are not curative, but may slow the deterioration rate of the patient. 

Cummings J. Drug therapy Alzheimer s disease. N Engl J Med 2004 351 56-67. 

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