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At the present time, the treatment of dementia with prescription medications has only minor benefits at high to very high costs. Only cholinesterase inhibitors and memantine (Namenda) have been approved by the FDA. Both are very expensive at the present time due to their patent protection. Both have very limited benefits which slightly delay the dementia. Donepezil (Aricept) was able to be imported very cheaply from India where the patent laws don't last 23 years like in the U.S.. In a sweetheart deal that the big drug companies obtained by bribing thousands of dishonest politicians in the U.S. and other countries, patent protection has been increased to 23 years. The drug companies managed just recently of get the Bush FDA to shut off access to cheap donepezil and many other drugs from India. Britain has stopped using donepezil for dementia because of it's very limited benefit. Memantine has an even worse cost-benefit ratio. The benefits of donepezil and memantine are quite minor. If people had to pay for them themselves, most people would rather leave the money for their children, i.e., the next generation. Somehow, saddling the next generation with massive public indebtedness is OK. Statins have not proven of any value in preventing dementia in the one huge study with the elderly which has been done. Anti-inflammatory medications like aspirin and ibuprofen have a lot of research showing some benefit for prevention but not for treatment. However, the side-effects clearly outweigh the potential benefits. Estrogen for women has some positive studies, but also at least one study finding no benefit. Again, the side-effects outweigh any benefits. The ACE inhibitor anti-depressant medication captopril might slow cognitive deterioration in hypertensives, but the research is very skimpy. In summary, medications to date don't offer much for treating or preventing dementia. Fortunately, many other interventions do appear to help prevent and possibly even treat dementia. Bright Light Helped AD Patients Sleep: In a 47 patient DB PC study of severe dementia, Harry Allen and E Jane Byrne of the Manchester Royal Infirmary found that 10 000 lux two hours daily for two weeks vs. 100 lux in an identical light box as the placebo had a beneficial effect. A nurse was with both sets of patients during the treatment. In the winter, patients receiving the bright light therapy slept for about 40 minutes longer than usual although there was no impact in spring or summer. BMJ 8/30/03 ACE Inhibitor Captopril May Be Better at Preventing Cognitive Deterioration: In a 1-year Japanese random assignment study of 162 patients with cognitive impairment and high blood pressure, those treated with brain-penetrating ACE inhibitors captopril or perindopril had only a 0.6 decline in their MMSE score vs. a 4.6 point decline with non-penetrating ACE inhibitors enalapril or imidapril and a 4.9 point decline with calcium channel blockers. Blood pressure was lowered to the normal range equally well with all the medications. Tokohu University, Neurol 10/2004. Ed: This study was not blinded, so needs to be repeated with more patients using a double-blind design. Captopril is very inexpensive costing about $3 per month (50 mg b.i.d.) wholesale and $13 per month retail. Perindopril (Aceon) is not available in the U.S. and costs $20 per month from Canada. Hypertension Treatment: Alzheimer's Reduced: In the Longitudinal Population Study in Sweden, the risk of dementia at age 80 is higher in people who had high blood pressure 15 years earlier (Lancet 347:1141, 1996). However, in the Honolulu Aisa study of 1,300 Japanese American men, Alzheimer's risk was 65% lower in those who had been treated for hypertension vs. those whose blood pressures were untreated (Stroke 37:1161, 2006). Clioquinol Helped in Alzheimer's in Small DB: A 36-patient 24-week DB PC study found patients with moderate to severe AD deteriorated only 1.5 points on their ADAS-cog Alzheimer's disease scores compared to an 8.9 point change on placebo. The FDA considers a 4 point difference significant. Clioquinol, a metal protein attenuating compound in development, binds zinc and copper. Univ College London. Arch Neurol 12/15/03. Doxycycline + Rifampin Helped AD in DB: In a randomized, triple-blind, controlled trial of 101 patients with probable AD and mild to moderate dementia, doxycycline 200 mg and rifampin 300 mg daily for 3 months resulted in significantly less decline in the SADAScog score at 6 months (-2.75 points, P=.034). At 12 months, the difference between groups in the SADAScog was -4.31 points (P=.079). The antibiotic group showed significantly less dysfunctional behavior at 3 months. There was no significant difference in adverse events between groups (P=.34). There were no differences in Chlamydia pneumoniae detection using polymerase chain reaction or antibodies (immunoglobulin (Ig)G or IgA) between groups. A randomized, controlled trial of doxycycline and rifampin for patients with Alzheimer's disease. Loeb MB, et al. Hamilton, Ontario, Canada. . McMaster Univ. J Am Geriatr Soc 2004 Mar;52(3):381-7. N-PEP-12 for Memory Loss: N-PEP-12 is a derivative of cerebrolysin. Cerebrolysin is a brain-derived neuropeptide compound that has been approved for the treatment of Alzheimer's disease (AD) in more than 30 countries. N-PEP-12 is much less potent, but it can be administered orally instead of IV. In a 30-day DB PC study of 54 adults over age 49 with age-related memory loss, those on N-PEP-12 did better on the ADAS-cog Memory score, the SKT, clinical ratings and some, but not all other tests. N-PEP-12 may be an effective treatment for memory loss in healthy older adults. Effects of N-PEP-12 on memory among older adults. Crook TH, Ferris SH, et al. EBEWE Pharma, Unterach, Austria. Int Clin Psychopharmacol. 2005 Mar;20(2):97-100 Omega-3 Helps Improve Alzheimers in a DB Study: Supplement to a 4:1 balance omega-6:omega-3 in DB PC study of 100 AD patients with 60 on fatty acid supplement found increased quality of life, mood, cooperation, appetite, sleep, short memory after 28 days. 49 of 60 showed some overall improvement. Previous rat studies by same researches with same supplement found increases in learning, thermoregulation, neurotoxin recovery, and seizure protection. Yehuda, Bar-Ilan Univ, Israel, Int J Neurosci 11/96 87:141-9 Omega-3: EFA and Anti-oxidants Help: 36 patients with Alzheimer's disease in a DB PC study. Those who were treated with essential fatty acids (fish oil) and anti-oxidants showed greater improvement vs. placebo in 20 wk study. Corrigan, Scotland, Ann NY Acad Sci ’91;640:250 Raising Glucose Helped: Glucose regulation disrupted in AD. Increasing in blood glucose has been found to help memory in AD pts. This causes a secondary increase in plasma insulin. Study holding glucose at fasting levels while causing hyperinsulinemia by IV found markedly memory improvement as well. Kraft, Wash U, Neurobiol Aging 2/96;17:123 Raloxifene May Lower Dementia Risk: In the 3-year DB PC MORE study of 5,386 post-menopausal women, compared to placebo, women on 120 mg/day of raloxifene had a 33% lower risk of mild cognitive impairment (RR=0.67) and lower risks of Alzheimer's disease (RR=0.52, not statistically significant). Those taking 60 mg/day of raloxifene did not do better than controls. 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. Ed: This study means that 200 women would have to take raloxifene for 3 years at a cost of $2 million to prevent one case of dementia from occurring. In all probability, it would only be delaying the dementia. The cost per year of benefit would appear very high. There are many lower cost interventions available. Anti-Hypertensives Anti-Hypertensives Help Afro-Americans: Of 1900 participants, 288 (15.2%) developed incident cognitive impairment during 5.8 year follow-up. Using logistic regression to control for the effects of age, sex, education, baseline cognitive scores, and hypertension and angina or myocardial infarction, antihypertensive medications reduced the odds of incident cognitive impairment by 38%. OR 0.62. Preservation of cognitive function with antihypertensive medications: a longitudinal analysis of a community-based sample of African Americans. Murray MD, Lane KA, Gao S, Evans RM, Unverzagt FW, Hall KS, Hendrie H. Arch Intern Med 2002 Oct 14;162(18):2090-6; Statins No Benefit for in Huge 3-Year DB Study: In a 3-year DB PC PROSPER study of 5,804 elderly average age 75 and at high risk for coronary heart disease, pravastatin was found to lower deaths from heart disease by 19% but had no effect on strokes or cognition. The NNT (number needed to treat to prevent one death of any cause) was not reported in the abstract. A prospective study of pravastatin in the elderly at risk: new hope for older persons. Shepherd J., University of Glasgow. Am J Geriatr Cardiol. 2004 May-Jun;13(3 Suppl):17-24 No Benefit in Large 5-Year Epidemiologic Study: In a 5-year follow-up of 2798 adults over age 64, there was no benefit from any of six statin medications or any of three other cholesterol medications on the percentage of elderly developing dementia. Compared with never use of lipin-lowering agents (LLAs), ever use of statins was not associated with the risk of all-cause dementia (multivariable-adjusted hazard ratio [HR], 1.08), Alzheimer disease alone (HR, 1.21), mixed Alzheimer disease and vascular dementia (HR, 0.87), or vascular dementia alone (HR, 1.36). In contrast, in secondary analyses, current use of statins compared with nonuse of LLAs was associated with HRs of 0.69 for all-cause dementia and 0.56 for any Alzheimer disease. Statin use and the risk of incident dementia: the Cardiovascular Health Study. Rea TD, et al. University of Washington, Seattle. . Arch Neurol. 2005 Jul;62(7):1047-51 Statins No Benefit in Epidemiologic Study: In cross-sectional and prospective community-based cohort studies, a random sample of 4,316 Medicare recipients, found that elevated levels of non-high-density lipoprotein (HDL-C) and low-density lipoprotein cholesterol (LDL-C) and decreased levels of HDL-C were weak risk factors for VaD in either cross-sectional or prospective analyses. Higher levels of total cholesterol were associated with a decreased risk of AD after adjustment for demographics, apolipoprotein E genotype, and cardiovascular risk factors. Treatment with drugs to lower lipid levels did not change the disease risk of either disorder. Relation of plasma lipids to Alzheimer disease and vascular dementia. Reitz C, Tang MX, Luchsinger J, Mayeux R. Columbia University. Arch Neurol. 2004 May;61(5):705-14 Statins May lower: Patients receiving lovastatin or pravastatin—but not simvastatin—had a 70% lower prevalence of Alzheimer’s disease than the entire patient population aged 60 and older (P<0.001 for each site). Moreover, patients receiving statins had a lower incidence (by 57-73%) of Alzheimer’s disease than patients receiving beta-blockers (by 73%), furosemide (furosemide) (by 57%), or captopril (by 64%). BMJ 2000;321:1040. Statins Lower Brain Cholesterol: UT Southwestern researchers report that participants who took statins lowered their brain cholesterol levels by 21.4 percent. Brain cholesterol is involved in the formation of amyloid plaques. Unlike dietary cholesterol, which is transported to the liver and excreted through the bile, the brain gets rid of cholesterol by first converting it into 24S-hydroxycholesterol, which is elevated in individuals with Alzheimer's disease. 44 AD patients with "normal" cholesterol DB a statin or niacin found 20% decrease in 24S- with a statin and 10% decrease with niacin. Archives of Neurology 4/22/03 Simvastatin Claimed to Help in Very Small DB: Professor Konrad Beyreuther, of the University of Heidelberg, Germany said 44 patients were randomized to receive either simvastatin or placebo in a 26-week DB PC. 16th European College of Neuropsychopharmacology conference in Prague. Reuters 9/22/03. Ed: Such reports, not yet subject to peer review, should be viewed very cautiously. Unfortunately, they are given far more media attention that they deserve. Indeed, this one didn't deserve any. Statins Might Help: 478 survivors of the 1932 Scottish Mental Health Survey (n=87,498) without dementia, who had been tested at age 11, were tested at age 80. After adjusting for sex, neuroactive drugs had a detrimental effect on life long cognitive change age (F=12.2, p=0.001, partial eta-squared=0.026), statins a beneficial effect (F=5.78, p=0.017, partial eta-squared=0.013) and polypharmacy a detrimental effect (F=6.46, p=0.011, partial eta-squared=0.014). In the optimal model estimated marginal means revealed: a relative improvement for statin users, IQ age 11=93.2 and age 80=100.6; compared with non-users, IQ age 11=100.9 and age 80=100.0. Life long changes in cognitive ability are associated with prescribed medications in old age. Starr JM, McGurn B, Whiteman M, Pattie A, Whalley LJ, Deary IJ. University of Edinburgh, Int J Geriatr Psychiatry. 2004 Apr;19(4):327-32 Other AD Studies Antibiotic May Help: Clioquinoline used in 1970s but caused rare neurological disease. Binds copper to zinc, both of which are present in sticky beta-amyloid plaques. The medicine decreased plaques by 51% vs. untreated mice. Soc Neurosci, AP 11/6/00 New Orleans. Catalase & Superoxide Dismutase Help Worms, Mice: Science 9/1/00 reports that Eukarion of Bedford, Mass. has shown that their synthetic enzymes thwart free radical damage in mice suffering strokes or conditions similar to AD or Parkinson’s and increase life-span of worms by 50%. Fruit flies given extra copies for superoxide dismutase live 33% longer. No side-effects in mice except at very high doses. Buck Institute for Age Research, Novato, Calif. GABA Helps Elderly Monkeys: 26-32 yo monkeys responded like 7-9yos to visual stimuli when given injection of GABA into brain. Science 5/2/03 Glutamate, Glycine, Choline, Pycnogenol: All promoted for AD prevention or treatment as well as L-deprenyl, piracetam, and hydergine. L-depreneyl supposedly in study of 17 patients at 10 mg/d for AD for 21 day and improvement. Hydergine: Hydergine does have at least 20 DB studies showing minor benefit. Average dosage 3 mg/d. However, benefit very minor and the medicine, despite being very inexpensive, is out of favor. Lecithin: Phosphotidylcholine: Tacrine with or without lecithin didn’t help al though maybe helped more severe. Dementia 12/96;7:260 Lecithin Small Added Value to Tacrine: Review of 5 studies found tacrine helps 1/3 and that lecithin has a small added value. Eur J Clin Pharm ‘94;47:17 Lecithin Review Finds No Evidence of Value Yet: Reviews 12 DB trials but they cover only 376 patients. Cochrane Database Syst Rev. 2003;(3):CD001015 NADH Helped in Small Study: Stabilized oral reduced nicotinamide adenine dinucleotide (NADH) on cognitive functioning in patients with Alzheimer's disease (AD). NADH is a coenzyme that plays a key role in cellular energy production and stimulates dopamine production. NADH has been shown to improve cognitive functioning in patients with Parkinson's disease, depression, and AD. In a 6-month, 26-patient DB PC trial of NADH (10 mg/day) or placebo, those treated with NADH showed no evidence of progressive cognitive deterioration and had significantly higher total scores on the MDRS compared with subjects treated with placebo (p < 0.05). Treatment of Alzheimer's disease with stabilized oral nicotinamide adenine dinucleotide: a randomized, double-blind study. Demarin V, Podobnik SS, Storga-Tomic D, Kay G. Sestre Milosrdnice University, Zagreb. Drugs Exp Clin Res. 2004;30(1):27-33; Other small studies have found benefit with chronic fatigue syndrome (Ann Allergy Asthma Immunol. 1999 Feb;82(2):185-91) and jet lag. Piracetam, Gingko, Nimodipine Most Pop in Germany: German MDs most frequently use piracetam 26%, gingko 24%, and nimodipine 14% although aspirin was cited by 29%. Pharmacopsychiatry 7/96;29:150-5. Calcium antagonists, and other nootropics also recommended early. Wien Med Wochenschr ’96;146:546-8. Piribedil: There is an age-dependent decline of dopamine D2-like receptor availability. In a 2-month crossover DB PC study of the D(2)/D(3) dopaminergic agonist piribedil (50 mg/day) of the cognitive skill learning in healthy elderly adults, piribedil showed a beneficial effect on the acquisition of a problem-solving routine, depending on the age of subjects, as revealed by solution reliability indexes measures. The effect of piribedil on the ability to learn to solve the puzzle was found to be dependent on the subject's working memory capacities. Psychopharmacology (Berl). 2004 May 12. Ed: Piribedil is used as an adjunctive medicine for early Parkinson's disease. Propentofylline May Help: Aventis is researching Propentofylline is a novel therapeutic agent for dementia that readily crosses the blood-brain barrier and acts by blocking the uptake of adenosine and inhibiting the enzyme phosphodiesterase. In vitro and in vivo its mechanism of action appears to be twofold; it inhibits the production of free radicals and reduces the activation of microglial cells. It therefore interacts with the inflammatory processes that are thought to contribute to dementia. Available research suggests may be of value but Aventis hasn’t released studies on 1200. Cochrane Database Syst Rev. 2003;(2):CD002853 Testosterone May Help: men with lower than normal testosterone levels have higher levels of beta amyloid protein in their blood. Women on HRT much lower risk of developing Alzheimer's disease. Maintaining normal levels of testosterone in ageing men, and adding testosterone to oestrogen supplements for postmenopausal women, could help reduce their risk of developing the disease. U Tx Houston, Proceedings of the National Academy of Sciences, New Scientist 1/21/02 Testosterone May Helped Helped in Brief Study: In a DB PC 6-week study of 15 Alzheimer and 17 mild cognitive impairment patients ages 63-85, those on weekly injections of 100 mg testosterone enanthate had improvements in spatial memory (p < 0.05) and constructional abilities (p < 0.05) and verbal memory. No changes were noted for selective and divided attention or language. Prostate specific antigen did not significantly change during this brief treatment. Testosterone improves spatial memory in men with Alzheimer disease and mild cognitive impairment. Cherrier MM, Matsumoto AM, et al. University of Washington, Seattle. Neurology. 2005 Jun 28;64(12):2063-8 Thomas E. Radecki, M.D., J.D. modern-psychiatry.com
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