Friday, February 13, 2009

Prevention of Alzheimer's Disease

In an interview with www.pharmexperts.com Zaven Khachaturian, PhD, former Director of the Office for Alzheimer's Disease Research at NIH and currently President of Lou Ruvo Brain Institute, emphasized the need for the preventive approach to the therapy of Alzheimer's disease (AD). In the following video Dr. Khachaturian reviews the current status of research on Alzheimer's disease and the need to find  new approaches to the prevention of this disease. This videointerview is also available on http://scivee.com/ .

The evidence that AD is preventable is rapidly accumulating. A review of current literature indicated that diet, vitamin supplementation as well as drugs may delay or prevent Alzheimer's pathology in the transgenic mice as well as the appearance of memory and learning deficits in elderly patients. The available information has to be rapidly disseminated to physicians, other medical professionals as well as potential patients. Preventive consultations with elderly patients alone have been shown in a large French study to reduce the incidence of AD (1).
Diet. Dietary approaches to prevention of AD include restrictions in the caloric intake as well as a decrease in the consumption of saturated fat. It has been reported that caloric restriction in AD transgenic mice (Tg2576) mediates activation of insulin receptor pathway leading to inactivation of a transcriptor factor (Fox03a). This effect has been correlated with the prevention of amyloid pathology (2). Diet rich in saturated fat has been shown to increase blood-to-brain delivery of amyloid beta (Abeta) (3). Mediterranean diet has been claimed to reduce the incidence of AD. According to Saura-Calixto and Goni (4) this diet should have a monosaturated/saturated fat ratio not in excess of 2 and total fat content not in excess of 62 g/person/day. In addition it should have high antioxidant capacity and phytosterols' content in excess of 400 mg/person/day.
Vitamins. The benefical effects of vitamin supplementation are controversial, although folic acid, 800 microg/day over 3 years has been reported to improve global functioning in AD patients (5). All-trans retinoic acid (ATRA, a metabolite of vitamin A) at 20 mg/kg orally 3 times weekly decreased Abeta deposition in the brain of 5-months old double transgenic mice (APP+PS1). It also reduced neuronal degeneration and improved learning and memory in these animals (6). There are many publications favoring the use of antioxidants, including vitamins C and E in the prevention of AD. A review of the existing literature led, however, to conclusion that long term prospective studies are still needed to justify its widespread use (7)
Drugs. Additional evidence has been recently published that non-steroidal antiinflammatory drugs (NSAIDs) are likely to prevent deposition of Abeta in the brain of animals. Lipopolysaccharide (LPS) has been shown to to increase Abeta 1-42 levels in the brain of mice. Sulindac sulfate (3.75 and 7.5 mg/kg orally, daily for 3 weeks) suppressed this effect (8). Use of statins was associated with the reduced risk for AD in patients (9). Valproic acid (an anticonvulsant) appears to prevent Abeta deposition in the brain of AD mice (10). In Russia cerebrolysin, a mixture of peptides from the pork brain, has been claimed to prevent cognitive deficits in elderly patients (11).
Summary. Animal studies and anecdotal clinical reports suggest that the onset of Alzheimer disease can be delayed or that disease may be prevented by diet, dietary supplements and/or drugs. Unfortunately, there are no reliable long-term clinical studies that clearly demostrate AD prevention. A regimen consisting of Mediterranian diet, supplemented with vitamins and antioxidants and combined with a NSAID or a statin can be expected to at least delay the onset of the disease.
Alex Scriabine M.D.
Keywords: Pharmacology - neuroscience - drug discovery - Alzheimer's disease - disease prevention - cognition
References: 1. Guyonnet G. et al. J. Nutrition, Health and Aging 520-9, 2008.
2. Quin W. et al Ann. NY Acad. Sci 1147:335-47, 2008.
3. Takeuchi R. et al. Atherosclerosis Supplements 9(2):19-25, 2008.
4. Saura-Calixto F. and Goni I. Crit. Reviews in Food Science and Nutrition 49(2):145-52, 2009.
5. Malouf R. and Grimley Evans J. Cochran Database Syst. Reviews (4) CD0045419, 2008.
6. Ding Y. et al J. Neuroscience 28(45):11622-34, 2008
7. Frank B. and Gupta S. Ann Clin Psychiatry 17(4):269-86,2005.
8. Lee JW et al. J. Inflammation 5:37, 2008
9. Sparks DL et al. Curr. Alzheimer Res. 5:416-21, 2008
10. Qing H et al J Exp Med 205:2781-9, 2008.
11. Gavrilova SI et al. J Neurology and Psychiatry (In Russian) 108:24-8, 2008

3 comments:

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