Drugs to Treat Alzheimer's Disease: Comparisons

Lane Simonian

There are two basic types of treatments for Alzheimer's disease: drugs that limit the formation of oxidants, and drugs/natural products that limit the formation of oxidants, remove them, and reverse part of the damage that they do to the brain. The second types of treatments are more effective.

To limit the formation of oxidants, you can either target a factor that causes the formation of the oxidant or inhibit a step in the process that leads to oxidation and nitration (oxidation and nitration damage key receptors, transport systems, and enzymes in the brain; in doing so they deplete the brain of neurotransmitters needed for the retrieval of short-term memory, sleep, social recognition, balanced mood, and alerteness, prevent the regeneration of neurons, and lead to the death of neurons). Anti-amyloid drugs such as Aduhelm, Leqembi, and donanemab remove one of the secondary factors--amyloid--that can cause oxidation and nitration. However, they do not help those without the APOE4 gene because non-carriers do not have enough amyloid to contribute to the onset and progression of the disease. Statistically, but perhaps not clinically, anit-amyloid drugs can produce a significant decline in the rate of progression in APOE4 carriers, but pulling out amyloid can result in brain swelling and brain bleeds.

A second group of drugs (sigma-1 receptor agonists) impede intracellular calcium release that can lead to oxidation and nitration in the brain. They may to a limited extent slow the progression of mild Alzheimer's disease in those with functioning sigma-1 receptors:

MMSE [Mini-Mental Examination] scores to one year (except 57 weeks for blarcamesine)

Galatamine (218 patients): 23.17 to 22.98

Aricept (498 patients): 22 to 21

Simufilam (216 patients): 21.5 to 20.3

Barcamesine (9 patients): 21 to 19.3 (rough calculation)

One estimate is that those on placebo, decline by an average of 2.3 points from a mean baseline of 21 at one year.At three years those on galantamine declined by 2.6 points, those on Aricept declined by 3.8 points, and those on blarcamesine at high concentrations declined by about one point (eight patients at 148 weeks).

Panax ginseng acts upstream of these drugs, so it helps those without a functioning sigma-1 receptor and it also acts downstream of the sigma-1 receptor so it may for awhile also help those with moderate Alzheimer's disease. In addition, it contains several compounds that are strong antioxidants. The following results then are to be expected:

Panax ginseng (high dose 9 grams): 21.4 to 22 to 24

Panax ginseng (low dose 4.5 grams): 22 to 25.7 to 23.7

If you combine treatments that limit the formation of oxidants, removes those oxidants, and reverses part of their damage to the brain, you may be able to largely stablize mild Alzheimer's disease for years and significantly reduce decline in those with moderate to severe Alzheimer's disease.