In the first part of this article (Psychiatric Times, June 2006, page 41), I pointed out that the numbers of patients with Alzheimer disease (AD), as well as those with severe cognitive impairment caused by traumatic brain injury and stroke, are continuing to increase. I noted that in addition to conventional pharmacologic treatments, promising research findings are being reported for many nonconventional treatments. In that column, I reviewed the more substantiated nonconventional approaches. This month, I look at some approaches for which the evidence is more limited.
HERBS AND SUPPLEMENTS
This compound herbal formula consists of 13 different herbs. It is used in Japanese traditional healing (Kampo) to treat cognitive impairment and frank dementia, as well as other psychiatric symptoms. Animal studies suggest that kami-untan-to (KUT) increases brain levels of both nerve growth factor and choline acetyltransferase, the enzyme that makes acetylcholine.1,2
In a 12-month open trial, 20 patients with moderate dementia and AD who received KUT alone and 7 who received a combined regimen of vitamin E(Drug information on vitamin e), estrogen, and a nonsteroidal anti-inflammatory drug deteriorated at a significantly slower rate than 32 control patients with moderate dementia who received no treatment.3 The beneficial effects of KUT were most notable 3 months into the study.
Golden root (Rhodiola rosea) was the object of intensive research in the former Soviet Union because of its use as a performance enhancer in athletes, soldiers, and cosmonauts. Psychiatric benefits are probably related to increased dopamine, serotonin, and norepinephrine(Drug information on norepinephrine) levels in the brain4 and include improved memory, increased mental stamina, and a general calming effect. Results from open studies suggest that golden root, 500 mg/d,improves overall mental performance and stamina in healthy persons5 and may accelerate return to normal cognitive functioning following traumatic brain injury. No studies on the use of golden root in dementia have been done.
This substance occurs naturally in the brain and liver. Its mechanism of action may involve stabilization of nerve cell membranes, stimulation of acetylcholine synthesis, and increased efficiency of mitochondrial energy production. Acetyl-l-carnitine (ALC) is widely used to treat and self-treat cognitive impairments related to dementia or other neurodegenerative diseases; however, findings from human clinical trials are inconsistent.6
Three small double-blind placebo-controlled studies show that ALC, 1500 to 3000 mg/d, improves overall performance on tests of reaction time, memory, and cognitive performance in patients with dementia and may slow the overall rate of progression of cognitive impairment.7-9 A Cochrane systematic review of 11 double-blind placebo-controlled studies of ALC in dementia confirmed significant positive effects at weeks 12 and 24, but these were not sustained at 1 year with continued treatment.10 ALC is well tolerated, and there are few reports of adverse effects.
Certain B vitamins are essential enzyme cofactors in the synthesis of neurotransmitters. A diet low in folic acid(Drug information on folic acid) and B12 leads to elevated blood levels of homocysteine and decreased synthesis of S-adenosyl methionine (SAMe), resulting in reduced synthesis of several neurotransmitters critical for normal cognitive functioning. Dietary deficiencies of folate and B12 eventually manifest as moderate to severe cognitive impairment.