Fish oil has been found to help in treatment in one double-blind placebo-controlled trial and fish consumption has been repeated associated with low rates of Alzheimer's.  It is good for so many diseases that everyone should be taking it. 

Estrogen, but not estrogen with medroxyprogesterone, has been found to help women prevent Alzheimer's, although more research is needed.  This can be given to women who have had hysterectomies, since there is no fear of increasing endometrial cancer.  There are other side-effects from estrogen.  Current research suggests that low-dose estrogen with drug free periods for women who still have a uterus may be acceptable. Ibuprofen might be useful, but its side-effects are probably too common to recommend it.

The B vitamins folate, and B-12 may also help prevent Alzheimer's.  Herbals including sage, lemon balm, ginkgo, and vinpocetine may be of benefit in prevention and treatment.  All have at least one double-blind trial each showing some benefit in treatment, although only ginkgo has enough double-blind trials to get a solid idea.  It appears only mildly beneficial.  I like sage and hope the research holds up since it is cheap and easy to add to your diet.  

Eating dark berries like blueberries, drinking grape juice, and eating spinach or other greens all look promising as does avoiding mammal meat, especially mammal fats (butter, cheese, whole milk, fatty meat) and trans fats, as much as possible.  Exercise, both physical and mental, appears to be a good way to reduce the risk of developing Alzheimer's. Alcohol drinking at one to six drinks per week and never over one per day appears to reduce Alzheimer's as does coffee and tea.  Be careful: too much alcohol is a common cause of dementia in France.  Fruits and vegetables in general are probably good.

Avoiding smoking and obesity appear to reduce the risk of developing dementia as does avoiding salt and keeping your blood pressure down.  Avoiding dietary aluminum is also be a good idea.  Of course, don't get knocked out, have a stroke, or suffer significant head trauma.  See these studies under Causation.

I am impressed with the animal research on melatonin, which is reviewed below.  Acetyl-l-carnitine may also be of preventive value.

Aging: Melatonin-induced Reduction in Age-related Oxidative Damage in Mice. Lipid peroxidation, GSSG and acid phosphatase were reduced (P < 0.001) in melatonin-treated mice. Age-induced decline in the level of GSH, GSH-Px and alkaline phosphatase activity were inhibited significantly by melatonin for 3 months starting at age 16 months. Manda K, Bhatia AL. University of Rajasthan, Jaipur, India. Biogerontology. 2003;4(3):133-9

Aging: Melatonin and Acetyl-L-Carnitine Each Partially Reverse Exploratory Behavior Decline in Aged Mice: 8 weeks treatment of 25-month-old mice also lowered elevated nitic oxide synthase 1 to youthful levels with ALCAR and partially restored them with melatonin. Sharman EH, et al. University of California Irvine, Irvine, CA. Brain Res. 2002 Dec 13;957(2):223-30.

Melatonin: Mouse Model Helped: Melatonin alleviates behavioral deficits associated with apoptosis and cholinergic system dysfunction in the APP 695 transgenic mouse model of Alzheimer's disease. Feng Z, et al. J Pineal Res. 2004 Sep;37(2):129-36; Similar findings with increased survival. J Neurochem. 2003 Jun;85(5):1101-8.

Melatonin: Mouse Model Not Helped:  Tg2576 transgenic mice with heavy amyloid plaques not helped by 4 months of melatonin from age 14 months. Quinn J, et al. Portland, OR, VA , Brain Res. 2005 Mar 10;1037(1-2):209-13.

Melatonin: Inhibiting Melatonin Biosynthesis Reduced Spatial Memory and Increased Tau Phosphorylation in Rats. Zhu LQ, et al. Huazhong University, Wuhan, China.

Melatonin: Prevents of Isoproterenol-induced Tau Hyperphosphorylation in the Rat: Wang XC, et al. Huazhong University, Wuhan, China. Sheng Li Xue Bao. 2005 Feb 25;57(1):7-12

Melatonin: Melatonin Blocks Haldol-Induced Hyperphosphorylation: Melatonin protects SH-SY5Y neuroblastoma cells from calyculin A-induced neurofilament impairment and neurotoxicity. Haloperidol is a specific inhibitor of 5-hydroxyindole-O-methyltransferase, a key enzyme in melatonin biosynthesis. Injection of haloperidol into the lateral ventricle and into peritoneal cavity compromises spatial memory retention of rats and induces hyperphosphorylation of microtubule-associated protein tau. Supplementation with melatonin by prior injection for 1 week and reinforcement during the haloperidol administration significantly improved memory retention deficits, arrested tau hyperphosphorylation and oxidative stress, and restored PP-2A activity. These results strongly support the involvement of decreased melatonin in Alzheimer-like spatial memory impairment and tau hyperphosphorylation, and PP-2A may play a role in mediating aberrant melatonin-induced lesions. J Pineal Res. 2004 Sep;37(2):71-7

Melatonin: Melatonin Helped Mouse Model: A transgenic (Tg) mouse model for Alzheimer's disease mimics the accumulation of senile plaques, neuronal apoptosis and memory impairment. Melatonin reduces beta-amyloid (Abeta)-induced neurotoxicity. In this four month study of 8 month old Tg mice, melatonin alleviated learning and memory deficits. Choline acetyltransferase (ChAT) activity also decreased in the frontal cortex and hippocampus of APP 695 Tg mice compared with non-Tg littermates. Melatonin supplementation increased ChAT activity in the frontal cortex and hippocampus. Melatonin reduced the number of apoptotic neurons. Melatonin decreased the Abeta deposits. Melatonin alleviates behavioral deficits associated with apoptosis and cholinergic system dysfunction in the APP 695 transgenic mouse model of Alzheimer's disease. Feng Z, et al. Peking Union Medical College, Beijing, China. J Pineal Res. 2004 Sep;37(2):129-36 

Melatonin: Improves Cognitive Impairment: Long-term effects of melatonin or 17 beta-estradiol on improving spatial memory performance in cognitively impaired, ovariectomized adult rats. Feng Z, et al. J Pineal Res. 2004 Oct;37(3):198-206

Melatonin May Help: Dietary supplementation results in a rise in endogenous melatonin in serum as well as other tissues. Elevated brain melatonin results in a significant reduction in levels of toxic cortical Abeta of both 40- and 42-amino-acid forms. Dietary melatonin supplementation may slow the neurodegenerative changes associated with brain aging and that the depletion of melatonin in the brain of aging mice may, in part, account for this adverse change. Lahiri DK, Chen D, et al. Indiana University. Ann N Y Acad Sci. 2004 Dec;1035:216-30

Melatonin: Isoproterenol-induced Tau Hyperphosphorylation Prevented by Melatonin Pretreatment in the rat. Wang

Raloxifene Very Minor Beneficial Effect: In the 3-year DB PC MORE study of 5,386 postmenopausal women with osteoporosis, 3.4% developed mild cognitive impairment, and 1.0% dementia. Compared to those taking placebo, women receiving 120 mg/day of raloxifene had a 33% lower risk of mild cognitive impairment (relative risk, 0.67; 95% confidence interval [CI], 0.46-0.98) and somewhat lower risks of Alzheimer's disease (relative risk=0.52, not significant) and any cognitive impairment (relative risk=0.73, not significant). Risks of mild cognitive impairment, Alzheimer's disease, and any impairment were not significantly different in the group taking 60 mg/day of raloxifene. Effect of Raloxifene on Prevention of Dementia and Cognitive Impairment in Older Women: The Multiple Outcomes of Raloxifene Evaluation (MORE) Randomized Trial. Yaffe K, Krueger K, et al. University of California, San Francisco. Am J Psychiatry. 2005 Apr;162(4):683-90.

Thomas E. Radecki, M.D., J.D.

modern-psychiatry.com