Page 174 - The Memory Program How to Prevent Memory Loss and Enhance Memory Power

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The relative failure of choline and lecithin, medications that directly enhance cholinergic function,
brings us back to the indirect strategy that led to the development and success of donepezil (Aricept):
inhibition of the enzyme acetylcholinesterase. No one really understands exactly why, but this
indirect route works much better than the direct approach. Among the cholinesterase inhibitors,
physostigmine, acetyl-l-carnitine, tacrine, and donepezil are the most prominent.

Physostigmine

Studies with the cholinesterase inhibitor physostigmine in small numbers of Alzheimer's patients,
some of which were conducted by my colleagues Drs. Yaakov Stern and Richard Mayeux, showed
superior memory test performance compared to placebo. The size of the improvement was
comparable to what would be shown years later with tacrine and donepezil, but physostigmine never
succeeded in the same fashion for two main reasons: the very short duration of action meant that pills
needed to be given five to six times daily, and it frequently caused nausea and other side effects.
Given these difficulties, using physostigmine to prevent age-related memory loss was never even
entertained as a concept. A long-acting physostigmine compound with single daily dosing was
developed, but this did not prove to be very effective, and physostigmine is now consigned to the
dust heap of history. I feel that this is unfortunate, because several of the Alzheimer's patients who
participated in the clinical trials at our center did show some benefit.

Properties of Acetyl-l-carnitine (Alcar)

Is found in muscle and helps get energy out of fat.
Can repair damage in lymphocytes, a type of white blood cell that is essential for normal
immune function.
Boosts metabolism within nerve cells, and slows the loss of nerve growth factor that helps
maintain the functioning of nerve cells in the hippocampus and frontal cortex. In fact, acetyl-l-
carnitine raises the levels of nerve growth factor by 30 to 40 percent in the brains of rats.
Prevents the loss of acetylcholinesterase, thereby indirectly enhancing cholinergic function.