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, 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 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 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.
1. Yabe T, Toriizuka K, Yamada H. Kami-untan-to (KUT) improves cholinergic deficits in aged rats. Phytomedicine. 1996;2:253-258.
2. Yabe T, Yamada H. Kami-untan-to enhances choline acetyl-transferase and nerve growth factor mRNA levels in brain cultured cells. Phytomedicine. 1996/1997;3: 361-367.
3. Arai H, Suzuki T, Sasaki H, et al. A new interventional strategy for Alzheimer's disease by Japanese herbal medicine [in Japanese]. Nippon Ronen Igakkai Zasshi. 2000;37:212-215.
4. Petkov VD, Stancheva SL, Tocuschieva L, Petkov VV. Changes in brain biogenic monoamines induced by the nootropic drugs adafenoxate and meclofenoxate and by citicholine (experiments on rats). Gen Pharmacol. 1990;21:71-75.
5. Spasov AA, Wikman GK, Mandrikov VB, et al. A double-blind, placebo-controlled pilot study of the stimulating and adaptogenic effect of Rhodiola rosea SHR-5 extract on the fatigue of students caused by stress during an examination period with a repeated low-dose regimen. Phytomedicine. 2000;7:85-89.
6. Pettegrew JW, Levine J, McClure RJ. Acetyl-l-carnitine physical-chemical, metabolic and therapeutic properties: relevance for its mode of action in Alzheimer's disease and geriatric depression. Mol Psychiatry. 2000;5:616-632.
7. Arrigo A, Casale R, Buonocore M, Ciano C. Effects of acetyl-l-carnitine on reaction times in patients with cerebrovascular insufficiency. Int J Clin Pharmacol Res. 1990;10:133-137.
8. Thal LJ, Carta A, Clarke WR, et al. A one-year multicenter placebo-controlled study of acetyl-l-carnitine in patients with Alzheimer's disease. Neurology. 1996;47:705-711.
9. Calvani M, Carta A, Caruso G, et al. Action of acetyl-l-carnitine in neurodegeneration and Alzheimer's disease. Ann N Y Acad Sci. 1992;663:483-486.
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11. Passeri M, Cucinotta D, Abate G, et al. Oral 59-methyltetrahydrofolic acid in senile organic mental disorders with depression: results of a double-blind multi-center study. Aging (Milano). 1993;5:63-71.
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17. Jama JW, Launer LJ, Witteman JC, et al. Dietary antioxidants and cognitive function in a population-based sample of older persons. The Rotterdam study. Am J Epidemiol. 1996;144:275-280.
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19. Zandi PP, Anthony JC, Khachaturian AS, et al. Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements; the Cache County Study. Arch Neurol. 2004;61:82-88.
20. Friess E, Trachsel L, Guldner J, et al. DHEA administration increases rapid eye movement sleep and EEG power in the sigma frequency range. Am J Physiol. 1995;268(1 pt 1):E107-E113.
21. Huppert F, Van Niekerk J. Dehydroepiandrosterone (DHEA) supplementation for cognitive function (Cochrane Review). In: The Cochrane Library, Issue 2. Chichester, UK: John Wiley & Sons, Ltd; 2004.
22. Azuma T, Nagai Y, Saito T, et al. The effect of dehydroepiandrosterone sulfate administration to patients with multi-infarct dementia. J Neurol Sci. 1999;162(1): 69-73.
23. Thorgrimsen L, Spector A, Wiles A, Orrell M. Aroma therapy for dementia (Cochrane Review). In: The Cochrane Library, Issue 2. Chichester, UK: John Wiley & Sons, Ltd; 2004.
24. Holmes C, Hopkins V, Hensford C, et al. Lavender oil as a treatment for agitated behaviour in severe dementia: a placebo controlled study. Int J Geriatr Psychiatry. 2002;17:305-308.
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29. Koger SM, Chapin K, Brotons M. Is music therapy an effective intervention for dementia? A meta-analytic review of literature. J Music Ther. 1999;36:2-15.
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