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Online Library: Alzheimer's Disease

The following pages provide an overview of the most recent research and clinical studies about the health benefits of micronutrients in fighting Alzheimer's disease. This collection of scientific facts proves that anyone who privately or publicly questions the health value of micronutrients does not serve YOUR health, or the health of the people, but rather the multi-billion dollar investment 'business with disease' based on patented pharmaceutical drugs.

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A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study.

Source: New England Journal of Medicine 1997;336(17):1216-22

Author: Sano M, Ernesto C, Thomas RG, Klauber MR, Schafer K, Grundman M, Woodbury P, Growdon J, Cotman CW, Pfeiffer E, Schneider LS, Thal LJ.

Affiliation:

Abstract: BACKGROUND: There is evidence that medications or vitamins that increase the levels of brain catecholamines and protect against oxidative damage may reduce the neuronal damage and slow the progression of Alzheimer's disease. METHODS: We conducted a double-blind, placebo-controlled, randomized, multicenter trial in patients with Alzheimer's disease of moderate severity. A total of 341 patients received the selective monoamine oxidase inhibitor selegiline (10 mg a day), alpha-tocopherol (vitamin E, 2000 IU a day), both selegiline and alpha-tocopherol, or placebo for two years. The primary outcome was the time to the occurrence of any of the following: death, institutionalization, loss of the ability to perform basic activities of daily living, or severe dementia (defined as a Clinical Dementia Rating of 3). RESULTS: Despite random assignment, the baseline score on the Mini-Mental State Examination was higher in the placebo group than in the other three groups, and this variable was highly predictive of the primary outcome (P<0.001). In the unadjusted analyses, there was no statistically significant difference in the outcomes among the four groups. In analyses that included the base-line score on the Mini-Mental State Examination as a covariate, there were significant delays in the time to the primary outcome for the patients treated with selegiline (median time, 655 days; P=0.012), alpha-tocopherol (670 days, P=0.001) or combination therapy (585 days, P=0.049), as compared with the placebo group (440 days). CONCLUSIONS: In patients with moderately severe impairment from Alzheimer's disease, treatment with selegiline or alpha-tocopherol slows the progression of disease.

Ascorbic acid in cerebrospinal fluid - a possible protection against free radicals in the brain.

Source: Archives of Gerontology and Geriatrics 1995;21(1):43-8.

Author: Barabás J, Nagy E, Degrell I.

Affiliation: Department of Psychiatry, University of Debrecen Medical School, Debrecen, Nagyerdei krt. 98., 4012 Hungary.

Abstract: Ascorbic acid and dehydroascorbate levels in the plasma and CSF of 12 patients with senile dementia of moderate grade Alzheimer's type were found to be significantly lower than 15 young, healthy volunteers. An intravenous infusion of 2 gm of ascorbic acid in 5 of these patients showed an active transport process for vitamin C from the plasma through the blood-CSF barrier. The study confirmed the free radical scavenging function of ascorbic acid in the central nervous system. Monitoring ascorbic acid levels in the plasma of demented patients is recommended because of its protective role in the free radical process that occurs in dementia. The amyloid precursor proteins aggregate only in the presence of free radicals. Vitamin C may reduce the harmful effects of free radicals in the brain.

Plasma concentrations of vitamins A and E and carotenoids in Alzheimer's disease.

Source: Age and Ageing. 1992;21(2):91-4.

Author: Zaman Z, Roche S, Fielden P, Frost PG, Niriella DC, Cayley AC.

Affiliation: Department of Chemical Pathology, Central Middlesex Hospital, London.

Abstract: This study of Alzheimer's and multi-infarct dementia patients, compared to nondemented elderly controls, found that in the 20 Alzheimer's and multi-infarct dementia patients there were significantly lower levels of vitamin E and beta-carotene than controls. Vitamin A was significantly reduced only in Alzheimer's disease patients. Vitamins A and E and the carotenoids act as free radical scavengers and their deficiency may increase the degenerative neurologic process in the brain and thereby exacerbate dementia.

Thiamine and Alzheimer's disease. A pilot study.

Source: Arch Neurol. 1988 Aug;45(8):833-5.

Author: Blass JP, Gleason P, Brush D, DiPonte P, Thaler H.

Affiliation: Will Rogers Institute, White Plains, NY.

Abstract: Seven females and 4 males who were between 59 and 83 years of age with Alzheimer's disease participated in a double-blind, placebo-controlled, crossover study evaluating the effects of 3 g/day of oral thiamin hydrochloride for 3 months compared with a placebo, 3 times daily. Results showed that the Mini-Mental State Examination was higher during the 3 months with 3 g/day of oral thiamin hydrochloride than with the placebo. These patients were not thiamin deficient in the conventional sense, malnourished or alcoholics.

Inositol treatment of Alzheimer's disease: a double blind, cross-over placebo controlled trial.

Source: Progress in neuro-psychopharmacology & biological psychiatry 1996 May;20(4):729-35

Author: Barak Y, Levine J, Glasman A, Elizur A, Belmaker RH.

Affiliation: Abarbanel Mental Health Center, Bat Yam, Israel.

Abstract: In a double-blind crossover study, inositol at 6 grams per day versus glucose for 1 month each was carried out in 11 Alzheimer's disease patients. There was an overall improvement in the Cognitive Subscale of the Cambridge Mental Disorder of the Elderly Examination (CAMDEX) with inositol but it was not significant. Language and orientation improved significantly more with inositol than the placebo. There were no serious side effects. The authors feel that higher doses of inositol should be studied in Alzheimer's disease patients for longer periods of time.

Progression from mild cognitive impairment to Alzheimer's Disease may be linked to depletion of antioxidant defenses

Source: Journal of Alzheimer's Disease 2010; 21(4):1165-77

Author: Baldeiras I, Santana I, et al

Affiliation: Laboratory of Neurochemistry, Neurology Department, Coimbra University Hospital, Coimbra, Portugal Center for Neuroscience and Cell Biology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal

Abstract: In a longitudinal study involving 70 patients with mild cognitive impairment at baseline, those who developed Alzheimer's disease were found to have a significant decrease in cellular antioxidant defenses (oxidized/reduced glutathione ratio and vitamin E), as compared to those who remained stable with mild cognitive impairment. The authors conclude, "These results suggest that accumulation of oxidative damage may start in pre-symptomatic phases of AD pathology and that progression to AD might be related to depletion of antioxidant defenses."

High Plasma Levels of Vitamin E Forms and Reduced Alzheimer's Disease Risk in Advanced Age

Source: Journal of Alzheimer's Disease, 2010; 20(4):1029-37

Author: Francesca Mangialasche, Miia Kivipelto, Patrizia Mecocci, Debora Rizzuto, Katie Palmer, Bengt Winblad, Laura Fratiglioni (Handling Associate Editor: D. Allan Butterfield)

Affiliation: Aging Research Center, Karolinska Institutet, Stockholm, Sweden.

Abstract: In this study we investigated the association between plasma levels of eight forms of vitamin E and incidence of Alzheimer's disease (AD) among oldest-old individuals in a population-based setting. In conclusion, high plasma levels of vitamin E are associated with a reduced risk of AD in advanced age. The neuroprotective effect of vitamin E seems to be related to the combination of different forms, rather than to α-tocopherol alone, whose efficacy in interventions against AD is currently debated.

25-Hydroxyvitamin D, dementia, and cerebrovascular pathology in elders receiving home services

Source: Neurology. 2010; 74 (1): 18-26

Author: J. S. Buell, PhD, B. Dawson-Hughes, MD, T. M. Scott, PhD, D. E. Weiner, MD, MS, G. E. Dallal, PhD, W. Q. Qui, MD, PhD, P. Bergethon, MD, I. H. Rosenberg, MD, M. F. Folstein, MD, S. Patz, PhD, R. A. Bhadelia, MD and K. L. Tucker, PhD

Affiliation: From the Friedman School of Nutrition Science and Policy (J.S.B., T.M.S., G.E.D., I.H.R., K.L.T.), Tufts University; Tufts Medical Center (T.M.S., D.E.W., W.Q.Q., M.F.F., S.P., R.A.B.), Tufts University School of Medicine; Jean Mayer USDA Human Nutrition Research Center on Aging (B.D.-H., G.E.D., I.H.R., K.L.T.); Beth Israel Deaconess Medical Center (R.A.B.); and Boston University Medical Center (P.B.), Boston, MA.

Abstract: Vitamin D insufficiency and deficiency was associated with all-cause dementia, Alzheimer disease, stroke (with and without dementia symptoms), and MRI indicators of cerebrovascular disease. These findings suggest a potential vasculoprotective role of vitamin D.

Omega-3 fatty acids: potential role in the management of early Alzheimer's disease.

Source: Clin Interv Aging. 2010; 5:45-61.

Author: Jicha GA, Markesbery WR.

Affiliation: University of Kentucky, Alzheimer's Disease Center and the Sanders-Brown Center on Aging University of Kentucky College of Medicine, Lexington, KY 40536-0230, USA.

Abstract: Several clinical trials investigating the effects of omega-3 fatty acid supplementation in AD have been completed and all failed to demonstrate its efficacy in the treatment of AD. However, these trials produced intriguing data suggesting that the beneficial effects of omega-3 fatty acid supplementation may depend on the stage of disease, other dietary mediators, and apolipoprotein E status.

Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial.

Source: International journal of geriatric psychiatry. 2011 Jul 21. doi: 10.1002/gps.2758.

Author: de Jager CA, Oulhaj A, Jacoby R, Refsum H, Smith AD.

Affiliation: OPTIMA, Nuffield Department of Clinical Medicine, University of Oxford, UK.

Abstract: Homocysteine is a risk factor for Alzheimer's disease. In the first report on the VITACOG trial, the authors showed that homocysteine-lowering treatment with B vitamins slows the rate of brain atrophy in mild cognitive impairment (MCI). Here they report the effect of B vitamins on cognitive and clinical decline (secondary outcomes) in the same study. In a double-blind, single-centre study, which included participants with MCI, aged ≥70 y, participants were randomly assigned to receive a daily dose of 0.8 mg folic acid, 0.5 mg vitamin B(12) and 20 mg vitamin B(6) (133 participants) or placebo (133 participants) for 2 y. Changes in cognitive or clinical function were analyzed by generalized linear models or mixed-effects models. Conclusion: In this small intervention trial, B vitamins appear to slow cognitive and clinical decline in people with MCI, in particular in those with elevated homocysteine. Further trials are needed to see if this treatment will slow or prevent conversion from MCI to dementia.

Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial.

Source: PLoS One. 2010;5(9):e12244.

Author: Smith AD, Smith SM, de Jager CA, Whitbread P, Johnston C, Agacinski G, Oulhaj A, Bradley KM, Jacoby R, Refsum H.

Affiliation: Oxford Project to Investigate Memory and Ageing, University of Oxford, UK.

Abstract: An increased rate of brain atrophy is often observed in older subjects, in particular those who suffer from cognitive decline. Homocysteine is a risk factor for brain atrophy, cognitive impairment and dementia. Plasma concentrations of homocysteine can be lowered by dietary administration of B vitamins. This study was done to determine whether supplementation with B vitamins that lower levels of plasma total homocysteine can slow the rate of brain atrophy in subjects with mild cognitive impairment in a randomised controlled trial (VITACOG, ISRCTN 94410159). In a single-center, randomized, double-blind controlled trial of high-dose folic acid, vitamins B(6) and B(12) were given to 271 individuals (of 646 screened) over 70 y old with mild cognitive impairment. A subset (187) volunteered to have cranial MRI scans at the start and finish of the study. Participants were randomly assigned to two groups of equal size, one treated with folic acid (0.8 mg/d), vitamin B(12) (0.5 mg/d) and vitamin B(6) (20 mg/d), the other with placebo; treatment was for 24 months. The main outcome measure was the change in the rate of atrophy of the whole brain assessed by serial volumetric MRI scans. Conclusions: The accelerated rate of brain atrophy in elderly with mild cognitive impairment can be slowed by treatment with homocysteine-lowering B vitamins. Sixteen percent of those over 70 y old have mild cognitive impairment and half of these develop Alzheimer's disease. Since accelerated brain atrophy is a characteristic of subjects with mild cognitive impairment who convert to Alzheimer's disease, trials are needed to see if the same treatment will delay the development of Alzheimer's disease.

Docosahexaenoic acid and synaptic protection in Alzheimer's disease mice.

Source: Biochimica et biophysica acta 2010;1801(8):791-8.

Author: Oster T, Pillot T.

Affiliation: Laboratoire Lipidomix (EA 4422), PRES de l'Université de Lorraine, ENSAIA - INPL, 54505 Vandoeuvre-lčs-Nancy, France.

Abstract: Alzheimer's disease (AD) is a major public health concern due to longer life expectancy in the Western countries. Amyloid-beta (Abeta) oligomers are considered the proximate effectors in the early stages of AD. AD-related cognitive impairment, synaptic loss and neurodegeneration result from interactions of Abeta oligomers with the synaptic membrane and subsequent activation of pro-apoptotic signaling pathways. Therefore, membrane structure and lipid status appear determinant in Abeta-induced toxicity. Numerous epidemiological studies have highlighted the beneficial influence of docosahexaenoic acid (DHA, C22:6 n-3) on the preservation of synaptic function and memory capacities in aged individuals or upon Abeta exposure, whereas its deficiency is presented as a risk factor for AD. An elevated number of studies have been reporting the beneficial effects of dietary DHA supplementation on cognition and synaptic integrity in various AD models. In this review, the authors describe the important potential of DHA to preserve neuronal and brain functions and classified its numerous molecular and cellular effects from impact on membrane lipid content and organisation to activation of signaling pathways sustaining synaptic function and neuronal survival. DHA appears as one of the most valuable diet ingredients whose neuroprotective properties could be crucial for designing nutrition-based strategies able to prevent AD as well as other lipid- and age-related diseases whose prevalence is progressing in elderly populations.

Tocopherols and tocotrienols plasma levels are associated with cognitive impairment

Source: Neurobiology of aging 2011 Dec 20. [Epub ahead of print]

Author: Mangialasche F, Xu W, Kivipelto M, Costanzi E, Ercolani S, Pigliautile M, Cecchetti R, Baglioni M, Simmons A, Soininen H, Tsolaki M, Kloszewska I, Vellas B, Lovestone S, Mecocci P; AddNeuroMed Consortium.

Affiliation: Aging Research Center, Karolinska Institutet, Stockholm, Sweden; Institute of Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy.

Abstract: Vitamin E includes 8 natural compounds (4 tocopherols, 4 tocotrienols) with potential neuroprotective activity. a-Tocopherol has mainly been investigated in relation to cognitive impairment. The authors examined the relation of all plasma vitamin E forms and markers of vitamin E damage (a-tocopherylquinone, 5-nitro-?-tocopherol) to mild cognitive impairment (MCI) and Alzheimer's disease (AD). Within the AddNeuroMed-Project, plasma tocopherols, tocotrienols, a-tocopherylquinone, and 5-nitro-?-tocopherol were assessed in 168 AD cases, 166 MCI, and 187 cognitively normal (CN) people. Compared with cognitively normal subjects, AD and MCI had lower levels of total tocopherols, total tocotrienols, and total vitamin E. In multivariable-polytomous-logistic regression analysis, both MCI and AD cases had 85% lower odds to be in the highest tertile of total tocopherols and total vitamin E, and they were, respectively, 92% and 94% less likely to be in the highest tertile of total tocotrienols than the lowest tertile. Further, both disorders were associated with increased vitamin E damage. Conclusion: Low plasma tocopherols and tocotrienols levels are associated with increased odds of MCI and AD.

Plasma tocopherols and risk of cognitive impairment in an elderly Italian cohort

Source: The American journal of clinical nutrition 2008 May;87(5):1306-13.

Author: Ravaglia G, Forti P, Lucicesare A, Pisacane N, Rietti E, Mangialasche F, Cecchetti R, Patterson C, Mecocci P

Affiliation: Department of Internal Medicine, Cardioangiology, and Hepatology, University Hospital Sant'Orsola-Malpighi, University of Bologna, Bologna, Italy.

Abstract: Evidence that vitamin E may preserve cognitive function in elderly subjects is conflicting. The most abundant and most investigated form of vitamin E in humans is alpha-tocopherol, but other antioxidant tocopherols (beta, gamma, and delta) exist in nature. The authors aimed to investigate plasma concentrations of the natural tocopherols and the tocopherol oxidation markers alpha-tocopherylquinone (alphaTQ) and 5-nitro-gamma-tocopherol (5NGT) in relation to cognitive function in the elderly. Baseline plasma tocopherols and their oxidation markers were measured in 761 elderly Italian subjects from a population-based cohort assessed in 1999-2000 for mild cognitive impairment (MCI) and dementia. In 2003-2004, information about cognitive status was collected for 615 of the 666 subjects without baseline cognitive impairment. Tocopherols and oxidation markers were analyzed as plasma absolute values divided by serum total cholesterol because lipids affect their blood availability. Analyses were adjusted for sociodemographic, genetic, lifestyle, and medical confounders. Compared with the corresponding lowest tertile, the risk of prevalent dementia was higher for the highest tertile of delta-tocopherol/cholesterol and alphaTQ/cholesterol, but the risk of incident dementia was not directly associated with plasma vitamin E metabolites. A U-shaped association, with lower risk for intermediate tertiles, was found for prevalent MCI with 5NGT/cholesterol and for incident dementia with gamma-tocopherol/cholesterol. Conclusion: Plasma concentrations of some non-alpha-tocopherol forms of vitamin E are associated with cognitive impairment in elderly people. However, the associations depend on concurrent cholesterol concentration and need further investigation.

Vitamin E levels, cognitive impairment and dementia in older persons: the InCHIANTI study

Source: Neurobiology of aging 2005 Jul;26(7):987-94.

Author: Cherubini A, Martin A, Andres-Lacueva C, Di Iorio A, Lamponi M, Mecocci P, Bartali B, Corsi A, Senin U, Ferrucci L

Affiliation: Institute of Gerontology and Geriatrics, University of Perugia Medical School, Department of Clinical and Experimental Medicine, via Brunamonti, Policlinico Monteluce, Padiglione E, Perugia 06122, Italy.

Abstract: There is conflicting evidence that antioxidants contribute to maintaining cognitive function in elderly subjects. The authors investigated whether vitamin E plasma levels are related to the presence of dementia and cognitive impairment in a population-based cohort study conducted in Italy. A total of 1033 participants aged at least 65 years received clinical and neuropsychological examinations, donated blood for vitamin E analysis and had their diets assessed. Participants with plasma vitamin E levels in the bottom tertile had a significantly higher probability of being demented and also of suffering from cognitive impairment compared to those in the highest vitamin E tertile after adjustment for age, gender, education, lipid levels, energy intake, vitamin E intake, and smoking. This study supports the notion that higher vitamin E plasma levels might provide significant protection against cognitive impairment and dementia in elderly subjects.

Low plasma N-3 fatty acids and dementia in older persons: the InCHIANTI study

Source: The journals of gerontology. Series A, Biological sciences and medical sciences 2007 Oct;62(10):1120-6

Author: Cherubini A, Andres-Lacueva C, Martin A, Lauretani F, Iorio AD, Bartali B, Corsi A, Bandinelli S, Mattson MP, Ferrucci L

Affiliation: Institute of Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy.

Abstract: N-3 fatty acids (FA) have an important role in brain development and function. However, there is conflicting evidence concerning the relationship between n-3 FA and dementia in older persons. In the Invecchiare in Chianti (InCHIANTI) study, the authors measured plasma FA by gas chromatography in 935 community-dwelling older persons randomly extracted from the population of two towns near Florence, Italy. Cognitive impairment was measured using the Mini-Mental Status Examination. Participants who scored

Mild cognitive deterioration with subcortical features: prevalence, clinical characteristics, and association with cardiovascular risk factors in community-dwelling older persons (The InCHIANTI Study).

Source: Journal of the American Geriatrics Society 2003 Aug;51(8):1064-71.

Author: Geroldi C, Ferrucci L, Bandinelli S, Cavazzini C, Zanetti O, Guralnik JM, Frisoni GB; InCHIANTI Study.

Affiliation: Laboratory of Epidemiology and Neuroimaging, IRCCS San Giovanni di Dio, Brescia, Italy.

Abstract: This study was conducted to identify subjects with minimal or mild non-amnestic cognitive impairment with parkinsonian stance and gait and investigate vascular correlates of this condition. The design of this study was a first wave of an epidemiological longitudinal study (InCHIANTI) on factors predicting loss of mobility in older persons, in the Chianti geographic area (Tuscany, Italy). Therefore 556 subjects aged 70 to 90 with Mini-Mental State Examination (MMSE) scores greater than 23 of 30, of the 1,260 persons aged 65 and older were randomly selected from the population registry of Greve in Chianti and Bagno a Ripoli, two small towns near Florence. Low cognitive performance (LCP) was defined as an age- and education-adjusted MMSE below the 50th percentile for the InCHIANTI population. Subcortical features were plastic rigidity on neurological examination (parkinsonism), gait disturbance (small-step gait or parkinsonian gait), and dysexecutive features. 243 participants had high cognitive performance, 166 had LCP without subcortical features, and 75 had LCP with subcortical features. Vascular risk factors were hypertension, atrial fibrillation or pathological findings on electrocardiogram (ECG), low serum high-density lipoprotein (HDL) or high low-density lipoprotein cholesterol, diabetes mellitus, obesity, and heavy smoking. 3 main vascular risk factors were significantly more prevalent in LCP with subcortical features: hypertension, atrial fibrillation or ECG changes, and low HDL cholesterol. LCP with subcortical features was significantly associated with cerebrovascular risk factors. Conclusion: Gait disturbance and non-amnestic cognitive symptoms might be the consequence of subcortical vascular damage.

An examination of the effects of the antioxidant Pycnogenol on cognitive performance, serum lipid profile, endocrinological and oxidative stress biomarkers in an elderly population

Source: Journal of Psychopharmacology 2008 Jul; 22(5):553-62.

Author: Ryan J, Croft K, Mori T, Wesnes K, Spong J, Downey L, Kure C, Lloyd J, Stough C

Affiliation: National Institute of Complementary Medicine (NICM)-Collaborative Centre for the Study of Natural Medicines and Neurocognition in Health and Disease, Brain Sciences Institute, Swinburne University of Technology, Hawthorn, Australia.

Abstract: The study examines the effects of the antioxidant flavonoid Pycnogenol on a range of cognitive and biochemical measures in healthy elderly individuals. The study used a double-blind, placebo-controlled, matched-pair design, with 101 elderly participants (60-85 years) consuming a daily dose of 150 mg of Pycnogenol for a three-month treatment period. Participants were assessed at baseline, then at 1, 2, and 3 months of the treatment. The control (placebo) and Pycnogenol groups were matched by age, sex, body mass index, micronutrient intake, and intelligence. The cognitive tasks comprised measures of attention, working memory, episodic memory, and psychomotor performance. The biological measures comprised levels of clinical hepatic enzymes, serum lipid profile, human growth hormone, and lipid peroxidation products. Statistically significant interactions were found for memory-based cognitive variables and lipid peroxidation products, with the Pycnogenol group displaying improved working memory and decreased concentrations of F2-isoprostanes* relative to the control group.

* markers of oxidative stress

How does pycnogenol influence oxidative damage to DNA and its repair ability in elderly people?

Source: Prague medical report 2010; 111(4):263-71.

Author: Dvoráková M, Paduchová Z, Muchová J, Duracková Z, Collins AR

Affiliation: Department of Medical Chemistry, Biochemistry and Clinical Biochemistry, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic.

Abstract: The purpose in this randomized, double blind, placebo controlled study was to find out the possible effect of a polyphenolic pine bark extract, Pycnogenol (Pyc) on the level of 8-oxo-7,8-dihydroguanine (8-oxoG) as representative of oxidative damage to DNA and on the DNA repair ability of elderly people. According to our results, three months of Pyc administration had no effect on the level of oxidative damage to DNA or on repair ability, but we found a relationship between the level of 8-oxoG and repair ability of DNA in this group. To conclude, even if the positive effect of Pyc was not confirmed in the case of elderly people it is important to highlight the necessity of further investigations about the mechanisms of Pyc acting on different age groups.

Red blood cell ω-3 fatty acid levels and markers of accelerated brain aging.

Source: Neurology 2012; 78(9):658-64.

Author: Tan ZS, Harris WS, Beiser AS, et al

Affiliation: Department of Medicine, Division of Geriatric Medicine, Easton Center for Alzheimer’s Disease Research, David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, USA.

Abstract: Higher dietary intake and circulating levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have been related to a reduced risk for dementia, but the pathways underlying this association remain unclear. The authors examined the cross-sectional relation of red blood cell (RBC) fatty acid levels to subclinical imaging and cognitive markers of dementia risk in a middle-aged to elderly community-based cohort. They related RBC DHA and EPA levels in dementia-free Framingham Study participants (n = 1575; 854 women, age 67 ± 9 years) to performance on cognitive tests and to volumetric brain MRI, with serial adjustments for age, sex, and education (model A, primary model), additionally for APOE ε4* and plasma homocysteine (model B), and also for physical activity and body mass index (model C), or for traditional vascular risk factors (model D). Participants with RBC DHA levels in the lowest quartile (Q1) when compared to others (Q2-4) had lower total brain and greater white matter hyperintensity volumes with persistence of the association with total brain volume in multivariable analyses. Participants with lower DHA and ω-3 index (RBC DHA+EPA) levels (Q1 vs. Q2-4) also had lower scores on tests of visual memory, executive function, and abstract thinking in model A, the results remaining significant in all models. Conclusion: Lower RBC DHA levels are associated with smaller brain volumes and a "vascular" pattern of cognitive impairment even in persons free of clinical dementia.

* The E4 variant is the largest known genetic risk factor for late-onset sporadic Alzheimer's Disease (AD) in a variety of ethnic groups.

The effects of multivitamins on cognitive performance: a systematic review and meta-analysis.

Source: Journal of Alzheimer's disease 2012;29(3):561-9.

Author: Grima NA, Pase MP, Macpherson H, Pipingas A.

Affiliation: Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Australia.

Abstract: Complementary medicine use is becoming increasingly popular with multivitamins being the most commonly used vitamin supplement. Although adequate vitamin and nutrient concentrations are necessary for optimal health and cognitive functioning, there is no scientific consensus as to whether multivitamin use prevents cognitive decline or improves mental functioning. The aim of the present study was to determine if multivitamins can be used efficaciously to improve cognitive abilities. A systematic review of randomized controlled trials was performed. Meta-analysis was performed on those cognitive tests used across the largest number of studies. Multiple electronic databases were searched until July 2011 by two authors. Randomized, placebo-controlled trials were considered appropriate if they reported on the chronic effects (≥1 month) of oral multivitamin supplementation on any valid cognitive outcomes. Ten trials were included in review (n = 3,200). Meta-analysis indicated that multivitamins were effective in improving immediate free recall memory but not delayed free recall memory or verbal fluency. There was no evidence of publication bias or heterogeneity. Other cognitive abilities sensitive to AD pathology, such as executive and visuospatial functions, were found to be under researched. In conclusion, multivitamins were found to enhance immediate free recall memory but no other cognitive domains.

1alpha,25-dihydroxyvitamin D3 interacts with curcuminoids to stimulate amyloid-beta clearance by macrophages of Alzheimer's disease patients.

Source: Journal of Alzheimer's disease 2009;17(3):703-17.

Author: Masoumi A, Goldenson B, Ghirmai S, Avagyan H, Zaghi J, Abel K, Zheng X, Espinosa-Jeffrey A, Mahanian M, Liu PT, Hewison M, Mizwickie M, Cashman J, Fiala M.

Affiliation: Department of Orthopaedic Surgery, UCLA School of Medicine, Los Angeles, USA.

Abstract: Patients with Alzheimer's disease (AD) suffer from brain amyloidosis* related to defective clearance of amyloid-beta (Abeta) by the innate immune system. To improve the innate immune system of AD patients, the authors studied immune stimulation of macrophages by 1alpha,25(OH)2-vitamin D3(1,25D3) in combination with curcuminoids*. AD patients' macrophages segregate into Type I (positively stimulated by curcuminoids regarding MGAT-III transcription) and Type II (not stimulated). In both Type I and Type II macrophages, 1,25D3 strongly stimulated Abeta phagocytosis and clearance while protecting against apoptosis. Certain synthetic curcuminoids in combination with 1,25D3 had additive effects on phagocytosis in Type I but not Type II macrophages. In addition, the authors investigated the mechanisms of 1,25D3 and curcuminoids in macrophages. The 1,25D3 genomic antagonist analog MK inhibited 1,25D3 but not curcuminoid effects, suggesting that 1,25D3 acts through the genomic pathway. In silico, 1,25D3 showed preferential binding to the genomic pocket of the vitamin D receptor, whereas bisdemethoxycurcumin showed preference for the non-genomic pocket. Conclusion: 1,25D3 is a promising hormone for AD immunoprophylaxis because in Type I macrophages combined treatment with 1,25D3 and curcuminoids has additive effects, and in Type II macrophages 1,25D3 treatment is effective alone. Human macrophages are a new paradigm for testing immune therapies for AD.

* Amyloidosis refers to a variety of conditions wherein amyloid proteins are abnormally deposited in organs or tissues and cause harm. Abeta is a form of amyloid proteins found in Alzheimer disease brain lesions.
* A curcuminoid is a curcumin or a derivative of a curcumin with different chemical groups that have been formed to increase solubility of curcumins.

Genomic and nongenomic signaling induced by 1α,25(OH)2-vitamin D3 promotes the recovery of amyloid-β phagocytosis by Alzheimer's disease macrophages.

Source: Journal of Alzheimer's disease 2012 Jan 1;29(1):51-62.

Author: Mizwicki MT, Menegaz D, Zhang J, et al

Affiliation: Department of Biochemistry, University of California, Riverside, USA.

Abstract: Brain clearance of amyloid-β (Aβ42) by innate immune cells is necessary for maintenance of normal brain function. Phagocytosis of soluble Aβ42 by Alzheimer's disease (AD) macrophages is defective, recovered in all "Type I and Type II" AD patients by 1α,25(OH)2-vitamin D3 (1,25D3) and blocked by the nuclear vitamin D receptor (VDR) antagonist (23S)-25-dehydro-1α(OH)-vitamin D3-26,23-lactone (MK). Conclusion: The structure-function results provide evidence that 1,25D3 activation of VDR-dependent genomic and nongenomic signaling, work in concert to recover dysregulated innate immune function in AD.

Higher vitamin D dietary intake is associated with lower risk of Alzheimer's disease: a 7-year follow-up.

Source: J Gerontol A Biol Sci Med Sci. 2012 Nov;67(11):1205-11.

Author: Annweiler C, Rolland Y, Schott AM, Blain H, Vellas B, Herrmann FR, Beauchet O.

Affiliation: Department of Neuroscience, Division of Geriatric Medicine, Angers University Hospital, 49933 Angers, France.

Abstract: Hypovitaminosis D is associated with cognitive decline among older adults. The relationship between vitamin D intakes and cognitive decline is not well understood. The objective of this study was to determine whether the dietary intake of vitamin D was an independent predictor of the onset of dementia within 7 years among women aged 75 years and older. 498 community-dwelling women (mean, 79.8 ± 3.8 years) free of vitamin D supplements from the EPIDemiology of OSteoporosis Toulouse cohort study were divided into 3 groups according to the onset of dementia within 7 years (ie, no dementia, Alzheimer's disease [AD], or other dementias). Baseline vitamin D dietary intakes were estimated from self-administered food frequency questionnaire. Age, body mass index, initial cognitive performance, education level, physical activity, sun exposure, disability, number of chronic diseases, hypertension, depression, use of psychoactive drugs, and baseline season were considered as potential confounders. Women who developed AD (n = 70) had lower baseline vitamin D intakes (mean, 50.3 ± 19.3 ěg/wk) than non-demented (n = 361; mean intake = 59.0 ± 29.9 ěg/wk) or those who developed other dementias (n = 67; mean intake = 63.6 ± 38.1 ěg/wk). There was no difference between other dementias and no dementia. Baseline vitamin D dietary intakes were associated with the onset of AD but not with other dementias. Being in the highest quintile of vitamin D dietary intakes was associated with a lower risk of AD compared with the lower 4 quintiles combined. Conclusion: Higher vitamin D dietary intake was associated with a lower risk of developing AD among older women.

Serum vitamin D deficiency as a predictor of incident non-Alzheimer dementias: a 7-year longitudinal study.

Source: Dement Geriatr Cogn Disord. 2011;32(4):273-8.

Author: Annweiler C, Rolland Y, Schott AM, Blain H, Vellas B, Beauchet O.

Affiliation: Department of Neuroscience, Division of Geriatric Medicine, Angers University Hospital, Angers University Memory Center, University of Angers, UNAM, Angers, France.

Abstract: Hypovitaminosis D has been cross-sectionally associated with dementia and stroke. The objective of this longitudinal study was to determine whether serum vitamin D deficiency at baseline could predict the onset of non-Alzheimer dementias (NAD) within 7 years among older women. 40 high-functioning older women (78.4 years, 76.4/82.0; median, 25th/75th percentile) from the EPIDOS Toulouse study were divided into 2 groups based on vitamin D deficiency (i.e., serum 25-hydroxyvitamin D <10 ng/ml) at baseline. At the end of the 7-year follow-up period, women matching the DSM-IV but not the NINCDS-ADRDA criteria were diagnosed with NAD while those matching the NINCDS-ADRDA criteria were considered to have Alzheimer's disease (AD). Subtle cognitive impairments at baseline, cardiovascular risk factors and Parkinson's disease were used as potential confounders. NAD was reported in 6 women (82.8 years, 80.6/86.0) after 7 years of follow-up. More NAD were observed in women with vitamin D deficiency. There was no between-group difference regarding the onset of AD. The authors found an association between vitamin D deficiency at baseline and the onset of NAD. Conversely, vitamin D deficiency was not associated with AD. Conclusion: Baseline vitamin D deficiency predicted the onset of NAD within 7 years among older women.

Preventing Alzheimer's disease-related gray matter atrophy by B-vitamin treatment.

Source: http://www.ncbi.nlm.nih.gov/pubmed/23690582

Author: Douaud G, Refsum H, de Jager CA, Jacoby R, Nichols TE, Smith SM, Smith AD.

Affiliation: Functional Magnetic Resonance Imaging of the Brain (FMRIB) Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, United Kingdom.

Abstract: Is it possible to prevent atrophy of key brain regions related to cognitive decline and Alzheimer's disease (AD)? One approach is to modify non-genetic risk factors, for instance by lowering elevated plasma homocysteine using B vitamins. In an initial, randomized controlled study on elderly subjects with increased dementia risk (mild cognitive impairment according to 2004 Petersen criteria), the authors showed that high-dose B-vitamin treatment (folic acid 0.8 mg, vitamin B6 20 mg, vitamin B12 0.5 mg) slowed shrinkage of the whole brain volume over 2 y. Here, the authors go further by demonstrating that B-vitamin treatment reduces, by as much as seven fold, the cerebral atrophy in those gray matter (GM) regions specifically vulnerable to the AD process, including the medial temporal lobe. In the placebo group, higher homocysteine levels at baseline are associated with faster GM atrophy, but this deleterious effect is largely prevented by B-vitamin treatment. The authors additionally show that the beneficial effect of B vitamins is confined to participants with high homocysteine (above the median, 11 µmol/L) and that, in these participants, a causal Bayesian network analysis indicates the following chain of events: B vitamins lower homocysteine, which directly leads to a decrease in GM atrophy, thereby slowing cognitive decline. Conclusion: The authors results show that B-vitamin supplementation can slow the atrophy of specific brain regions that are a key component of the AD process and that are associated with cognitive decline.

B vitamins slow brain atrophy in people with memory problems

Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial

Source: PLoS ONE 5(9): e12244. doi:10.1371/journal.pone.0012244

Author: Smith AD, Smith SM, de Jager CA, Whitbread P, Johnston C, et al.

Affiliation: Oxford Project to Investigate Memory and Ageing (OPTIMA), University of Oxford, Oxford, United Kingdom, University Department of Pharmacology and Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, United Kingdom, Department of Clinical Neurology, Oxford Centre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford, Oxford, United Kingdom, Department of Radiology and Nuclear Medicine, Oxford Radcliffe Hospitals NHS Trust, Oxford, United Kingdom, University Department of Psychiatry, University of Oxford, Oxford, United Kingdom, Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway

Abstract: An increased rate of brain atrophy is often observed in older subjects, in particular those who suffer from cognitive decline. Homocysteine is a risk factor for brain atrophy, cognitive impairment and dementia. Plasma concentrations of homocysteine can be lowered by dietary administration of B vitamins. The study was done to determine whether supplementation with B vitamins that lower levels of plasma total homocysteine can slow the rate of brain atrophy in subjects with mild cognitive impairment in a randomised controlled trial. Single-center, randomized, double-blind controlled trial of high-dose folic acid (0.8 mg/d), vitamins B6 (20 mg/d) and B12 (0.5 mg/d) in 271 individuals over 70 y old with mild cognitive impairment. Participants were randomly assigned to two groups of equal size, one treated with folic acid, vitamin B12 and vitamin B6, the other with placebo; treatment was for 24 months. The main outcome measure was the change in the rate of atrophy of the whole brain assessed by serial volumetric MRI scans. Conclusions: The accelerated rate of brain atrophy in elderly with mild cognitive impairment can be slowed by treatment with homocysteine-lowering B vitamins. Sixteen percent of those over 70 y old have mild cognitive impairment and half of these develop Alzheimer's disease. Since accelerated brain atrophy is a characteristic of subjects with mild cognitive impairment who convert to Alzheimer's disease, trials are needed to see if the same treatment will delay the development of Alzheimer's disease.