X-Message-Number: 29312 Date: Thu, 15 Mar 2007 10:42:11 -0800 (PST) From: Subject: reversing Alzheimer's [Combination therapy may be able to partially reverse dementia now.] Am J Alzheimers Dis Other Demen. 2005 Jan-Feb;20(1):21-6. Integrated treatment approach improves cognitive function in demented and clinically depressed patients. Bragin V, Chemodanova M, Dzhafarova N, Bragin I, Czerniawski JL, Aliev G. Stress Relief and Memory Training Center, Brooklyn, New York, USA. The purpose of this study was to evaluate the efficacy of an integrative treatment approach on cognitive performance. The study sample comprised 35 medically ill patients (20 male, 15 female) with an average age of 71.05, who were diagnosed with mild dementia and depression. These patients were evaluated at baseline and at six, 12, and 24 months of treatment, which included antidepressants (sertraline, citalopram, or venlafaxine XR, alone or in combination with bupropion XR), cholinesterase inhibitors (donepezil, rivastigmine or galantamine), as well as vitamins and supplements (multivitamins, vitamin E, alpha-lipoic acid, omega-3 and coenzyme Q-10). Patients were encouraged to modify their diet and lifestyle and perform mild physical exercises. Results show that the integrative treatment not only protracted cognitive decline for 24 months but even improved cognition, especially memory and frontal lobe functions. PMID: 15751450 Drugs Exp Clin Res. 2004;30(1):27-33. 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. Department of Neurology, Sestre Milosrdnice University Hospital, Zagreb, Croatia. This study was designed to evaluate the effect of 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. In previous trials NADH has been shown to improve cognitive functioning in patients with Parkinson's disease, depression and AD. The present trial was a randomized, placebo-controlled, matched-pairs, double-blind, 6-month clinical study. Patients with probable AD (n = 26) were randomized to receive either stabilized oral NADH (10 mg/day) or placebo. Twelve pairs of subjects were matched for age and baseline total score on the Mattis Dementia Rating Scale (MDRS) and the Mini Mental State Examination. After 6 months of treatment, subjects 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). Analysis of MDRS subscales revealed significantly better performance by NADH subjects on measures of verbal fluency (p = 0.019), visual-constructional ability (p = 0.038) and a trend (p = 0.08) to better performance on a measure of abstract verbal reasoning. There were no differences between groups in measures of attention, memory, or in clinician ratings of dementia severity (Clinical Dementia Rating). Consistent with earlier studies, the present findings support NADH as a treatment for AD. PMID: 15134388 Arch Neurol. 2006 Oct;63(10):1402-8. Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial. Freund-Levi Y, Eriksdotter-Jonhagen M, Cederholm T, Basun H, Faxen-Irving G, Garlind A, Vedin I, Vessby B, Wahlund LO, Palmblad J. Department of Neurobiology, Caring Sciences and Society, Section of Clinical Geriatrics, Karolinska University Hospital Huddinge, Stockholm. BACKGROUND: Epidemiologic and animal studies have suggested that dietary fish or fish oil rich in omega-3 fatty acids, for example, docosahexaenoic acid and eicosapentaenoic acid, may prevent Alzheimer disease (AD). OBJECTIVE: To determine effects of dietary omega-3 fatty acid supplementation on cognitive functions in patients with mild to moderate AD. DESIGN: Randomized, double-blind, placebo-controlled clinical trial. PARTICIPANTS: Two hundred four patients with AD (age range [mean +/- SD], 74 +/- 9 years) whose conditions were stable while receiving acetylcholine esterase inhibitor treatment and who had a Mini-Mental State Examination (MMSE) score of 15 points or more were randomized to daily intake of 1.7 g of docosahexaenoic acid and 0.6 g of eicosapentaenoic acid (omega-3 fatty acid-treated group) or placebo for 6 months, after which all received omega-3 fatty acid supplementation for 6 months more. MAIN OUTCOME MEASURES: The primary outcome was cognition measured with the MMSE and the cognitive portion of the Alzheimer Disease Assessment Scale. The secondary outcome was global function as assessed with the Clinical Dementia Rating Scale; safety and tolerability of omega-3 fatty acid supplementation; and blood pressure determinations. RESULTS: One hundred seventy-four patients fulfilled the trial. At baseline, mean values for the Clinical Dementia Rating Scale, MMSE, and cognitive portion of the Alzheimer Disease Assessment Scale in the 2 randomized groups were similar. At 6 months, the decline in cognitive functions as assessed by the latter 2 scales did not differ between the groups. However, in a subgroup (n = 32) with very mild cognitive dysfunction (MMSE >27 points), a significant (P<.05) reduction in MMSE decline rate was observed in the omega-3 fatty acid-treated group compared with the placebo group. A similar arrest in decline rate was observed between 6 and 12 months in this placebo subgroup when receiving omega-3 fatty acid supplementation. The omega-3 fatty acid treatment was safe and well tolerated. CONCLUSIONS: Administration of omega-3 fatty acid in patients with mild to moderate AD did not delay the rate of cognitive decline according to the MMSE or the cognitive portion of the Alzheimer Disease Assessment Scale. However, positive effects were observed in a small group of patients with very mild AD (MMSE >27 points). PMID: 17030655 Nutr Neurosci. 2003 Jun;6(3):153-62. Blueberry supplementation enhances signaling and prevents behavioral deficits in an Alzheimer disease model. Joseph JA, Denisova NA, Arendash G, Gordon M, Diamond D, Shukitt-Hale B, Morgan D. USDA-HNRCA at Tufts University, 711 Washington Street, Boston, MA 02111, USA. Previously, we showed that blueberry (BB) supplementation reversed the deleterious effects of aging on motor behavior and neuronal signaling in senescent rodents. We now report that BB-fed (from 4 months of age) APP + PS1 transgenic mice showed no deficits in Y-maze performance (at 12 months of age) with no alterations in amyloid beta burden. It appeared that the protective mechanisms are derived from BB-induced enhancement of memory-associated neuronal signaling (e.g. extracellular signal-regulated kinase) and alterations in neutral sphingomyelin-specific phospholipase C activity. Thus, our data indicate for the first time that it may be possible to overcome genetic predispositions to Alzheimer disease through diet. PMID: 12793519 Am J Med. 2006 Sep;119(9):751-9. Fruit and vegetable juices and Alzheimer's disease: the Kame Project. Dai Q, Borenstein AR, Wu Y, Jackson JC, Larson EB. Department of Medicine, Division of General Internal Medicine and Public Health, Vanderbilt Center for Health Services Research, Vanderbilt-Ingram Cancer Center, Vanderbilt School of Medicine, Nashville, Tenn, USA. BACKGROUND: Growing evidence suggests that oxidative damage caused by the beta-amyloid peptide in the pathogenesis of Alzheimer's disease may be hydrogen peroxide mediated. Many polyphenols, the most abundant dietary antioxidants, possess stronger neuroprotection against hydrogen peroxide than antioxidant vitamins. METHODS: We tested whether consumption of fruit and vegetable juices, containing a high concentration of polyphenols, decreases the risk of incident probable Alzheimer's disease in the Kame Project cohort, a population-based prospective study of 1836 Japanese Americans in King County, Washington, who were dementia-free at baseline (1992-1994) and were followed through 2001. RESULTS: After adjustment for potential confounders, the hazard ratio for probable Alzheimer's disease was 0.24 (95% confidence interval [CI], 0.09-0.61) comparing subjects who drank juices at least 3 times per week with those who drank less often than once per week with a hazard ratio of 0.84 (95% CI, 0.31-2.29) for those drinking juices 1 to 2 times per week (P for trend < .01). This inverse association tended to be more pronounced among those with an apolipoprotein Eepsilon-4 allele and those who were not physically active. Conversely, no association was observed for dietary intake of vitamins E, C, or beta-carotene or tea consumption. CONCLUSIONS: Fruit and vegetable juices may play an important role in delaying the onset of Alzheimer's disease, particularly among those who are at high risk for the disease. These results may lead to a new avenue of inquiry in the prevention of Alzheimer's disease. PMID: 16945610 Neurobiol Aging. 2005 Dec;26 Suppl 1:133-6. Epub 2005 Nov 2. Prevention of Alzheimer's disease: Omega-3 fatty acid and phenolic anti-oxidant interventions. Cole GM, Lim GP, Yang F, Teter B, Begum A, Ma Q, Harris-White ME, Frautschy SA. Greater Los Angeles Veterans Affairs Healthcare System, Geriatric Research, Education and Clinical Center, Sepulveda, CA 91343, USA. Alzheimer's disease (AD) and cardiovascular disease (CVD) are syndromes of aging that share analogous lesions and risk factors, involving lipoproteins, oxidative damage and inflammation. Unlike in CVD, in AD, sensitive biomarkers are unknown, and high-risk groups are understudied. To identify potential prevention strategies in AD, we have focused on pre-clinical models (transgenic and amyloid infusion models), testing dietary/lifestyle factors strongly implicated in reducing risk in epidemiological studies. Initially, we reported the impact of non-steroidal anti-inflammatory drugs (NSAIDs), notably ibuprofen, which reduced amyloid accumulation, but suppressed few inflammatory markers and without reducing oxidative damage. Safety concerns with chronic NSAIDs led to a screen of alternative NSAIDs and identification of the phenolic anti-inflammatory/anti-oxidant compound curcumin, the yellow pigment in turmeric that we found targeted multiple AD pathogenic cascades. The dietary omega-3 fatty acid, docosahexaenoic acid (DHA), also limited amyloid, oxidative damage and synaptic and cognitive deficits in a transgenic mouse model. Both DHA and curcumin have favorable safety profiles, epidemiology and efficacy, and may exert general anti-aging benefits (anti-cancer and cardioprotective.). PMID: 16266772 J Neurosci. 2001 Nov 1;21(21):8370-7. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM. Departments of Medicine and Neurology, University of California, Los Angeles, Los Angeles, California 90095, USA. Inflammation in Alzheimer's disease (AD) patients is characterized by increased cytokines and activated microglia. Epidemiological studies suggest reduced AD risk associates with long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs). Whereas chronic ibuprofen suppressed inflammation and plaque-related pathology in an Alzheimer transgenic APPSw mouse model (Tg2576), excessive use of NSAIDs targeting cyclooxygenase I can cause gastrointestinal, liver, and renal toxicity. One alternative NSAID is curcumin, derived from the curry spice turmeric. Curcumin has an extensive history as a food additive and herbal medicine in India and is also a potent polyphenolic antioxidant. To evaluate whether it could affect Alzheimer-like pathology in the APPSw mice, we tested a low (160 ppm) and a high dose of dietary curcumin (5000 ppm) on inflammation, oxidative damage, and plaque pathology. Low and high doses of curcumin significantly lowered oxidized proteins and interleukin-1beta, a proinflammatory cytokine elevated in the brains of these mice. With low-dose but not high-dose curcumin treatment, the astrocytic marker GFAP was reduced, and insoluble beta-amyloid (Abeta), soluble Abeta, and plaque burden were significantly decreased by 43-50%. However, levels of amyloid precursor (APP) in the membrane fraction were not reduced. Microgliosis was also suppressed in neuronal layers but not adjacent to plaques. In view of its efficacy and apparent low toxicity, this Indian spice component shows promise for the prevention of Alzheimer's disease. PMID: 11606625 Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=29312