It is known that homocysteine is a risk factor for Alzheimer disease, but recently it has been reported that treatment to lower homocysteine had no effect for Alzheimer dementia, which suggests two possible explanations. One is that homocysteine's role as a risk factor may be doubtful, and the other is that there may be another possibility. I would like to discuss this other possibility: that homocysteic acid may be metabolized not only from homocysteine, but may also be metabolized from methionine (1). This might explain why treatment to reduce homocysteine alone would not be effective for Alzheimer dementia, because this treatment would not by itself lower homocysteic acid. Thus, we should not consider that homocysteine per se is a risk factor for Alzheimer dementia, but that homocysteic acid is the true risk factor.

References:
1. Do KQ, Benz B, Binns KE, Eaton SA, Salt TE. Release of homocysteic acid from rat thalamus following stimulation of somatosensory afferents in vivo: feasibility of glial participation in synaptic transmission. Neuroscience. 2004;124(2):387-93. Abstract

View all comments by Tohru Hasegawa

Dramatic improvements in cognition are available to patients whose hyperhomocysteinemia is not improved by adjusting folic acid and B-12 defietary intake but who have polymorphisms for enzymes in the pathways of methionine metabolism. The most common polymorphisms in this area are in MTHFR (methylene tetra-hydro folate reductase). When such polymorphisms are found on blood testing, and when high doses of methyl folate are used for replacement, cognitive performance usually improves.

Another fact in the connection between homocysteine and dementia is that methotrexate is damaging to people with this MTHFR polymorphism, so they can be hurt by taking methotrexate, even for a valid reason such as rheumatoid arthritis.

It is necessary to consider the amount of profit being made on pharmaceuticals such as acetylcholinesterase inhibitors when trying to sort out the politics of dementia research. I recently learned that memantine can cause paranoia and anxiety in some patients. When this drug is prescribed to demented patients, does the development of paranoic ideation and/or...  Read more

Dramatic improvements in cognition are available to patients whose hyperhomocysteinemia is not improved by adjusting folic acid and B-12 defietary intake but who have polymorphisms for enzymes in the pathways of methionine metabolism. The most common polymorphisms in this area are in MTHFR (methylene tetra-hydro folate reductase). When such polymorphisms are found on blood testing, and when high doses of methyl folate are used for replacement, cognitive performance usually improves.

Another fact in the connection between homocysteine and dementia is that methotrexate is damaging to people with this MTHFR polymorphism, so they can be hurt by taking methotrexate, even for a valid reason such as rheumatoid arthritis.

It is necessary to consider the amount of profit being made on pharmaceuticals such as acetylcholinesterase inhibitors when trying to sort out the politics of dementia research. I recently learned that memantine can cause paranoia and anxiety in some patients. When this drug is prescribed to demented patients, does the development of paranoic ideation and/or worsening of anxiety come from the drug or the disease? I suspect the design of the homocysteine experiments for cure rather than prevention is no accident. When homocysteine correction is shown to be ineffectual for treatment, prevention is forgotten and the cash cow (i.e. dementia) is preserved.

View all comments by Laura Fisher