ALZHEIMER'S DISEASE

In this section we will provide scientific studies related to the ingredients contained in the NMS Neuromuscular Support Formula that deal with Alzheimer's Disease. This is additional information that we feel relates to the efficacy of this amazing product and should also give you an idea of the breadth and scope of the information about the ingredients in the NMS Formula dealing with health conditions other than Pain & Inflammation.

ALZHEIMER'S DISEASE --- THIAMINE

Antioxid Redox Signal. 2007 Aug 8; [Epub ahead of print]
Thiamine-Dependent Processes and Treatment Strategies in Neurodegeneration.
Gibson GE, Blass JP.
Department of Neurology and Neurosciences, Weill Medical College of Cornell University, Burke Medical Research Institute, White Plains, New York.

Reductions in brain glucose metabolism and increased oxidative stress invariably occur in Alzheimer's disease (AD) and thiamine (vitamin B1) deficiency. Both conditions cause irreversible cognitive impairment; their behavioral consequences overlap but are not identical. Thiamine-dependent processes are critical in glucose metabolism, and recent studies implicate thiamine in oxidative stress, protein processing, peroxisomal function, and gene expression. The activities of thiamine-dependent enzymes are characteristically diminished in AD, and the reductions in autopsy AD brain correlate highly with the extent of dementia in the preagonal state. Abnormalities in thiamine-dependent processes can be plausibly linked to the pathology of AD. Seemingly paradoxical properties of thiamine-dependent processes may underlie their relation to the pathophysiology of AD: Reduction of thiamine-dependent processes increase oxidative stress. Thiamine can act as a free radical scavenger. Thiamine-dependent mitochondrial dehydrogenase complexes produce oxygen free radicals and are sensitive to oxidative stress. Genetic disorders of thiamine metabolism that lead to neurological disease can be treated with large doses of thiamine. Although thiamine itself has not shown dramatic benefits in AD patients, the available data is scanty. Adding thiamine or more absorbable forms of thiamine to tested treatments for the abnormality in glucose metabolism in AD may increase their efficacy.

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Gerontology. 1999;45(2):96-101.
Clinical relevance of thiamine status amongst hospitalized elderly patients.
Pepersack T, Garbusinski J, Robberecht J, Beyer I, Willems D, Fuss M.
Division of Geriatric Medicine, Brugmann University Hospital, Free University of Brussels, Belgium.

BACKGROUND: The prevalence and the consequences of thiamine deficiency among elderly patients admitted to acute geriatric wards are not known. OBJECTIVES: (1) To assess the prevalence of thiamine deficiency in patients admitted to a geriatric ward compared to age-matched ambulatory outpatients; (2) to identify their diseases and problems associated with thiamine deficiency, and (3) to determine the relationship between the thiamine status and the cognitive and functional status of these patients. MATERIALS AND METHODS: 118 aged hospitalized patients (83 +/- 7 years; mean age +/- SD) were prospectively enrolled on admission to the geriatric ward. Their cognitive status was assessed using the Mini-Mental State Examination (MMSE) and their ability to perform their activities of daily living (ADL) using ADL scales. The effect of exogenous thiamine pyrophosphate (TPP) addition on the blood transketolase (TK) activity (TPP TK effect) served to estimate thiamine deficiency. Socioeconomic data, diseases and treatment were identified as potential associated risk factors. This group of hospitalized patients was divided according to their thiamine status to characterize the conditions associated with thiamine deficiency. Thirty-five outpatients without any functional or cognitive impairment served as a control group. RESULTS: Of 118 inpatients, 46 (39%) presented with a TPP TK effect of >15%, and 6 with values of >22%, indicating moderate and severe thiamine deficiency, respectively. Only 6 of 30 outpatients (20%) exhibited a TPP TK effect of >15% and none of them reached values of >18%. Although it tended to be lower in outpatients, the mean TPP TK effect did not statistically differ from the mean of inpatients. Thiamine-deficient inpatients comprised a larger proportion of institutionalized subjects than nondeficient inpatients (87 versus 47%, p < 0.001). Functional status, cognitive functions and the occurrence of delirium did not differ according to their thiamine status. By contrast, thiamine-deficient inpatients exhibited a higher proportion of Alzheimer's disease, depression, cardiac failure and falls. Furosemide was more frequently taken by thiamine-deficient patients. CONCLUSIONS: Severe thiamine deficiency remained quite low among the hospitalized elderly. The prevalence of moderate thiamine deficiency approached 40%. Institutionalized subjects were at particular risk of developing thiamine deficiency. Its clinical relevance on functional status and on cognitive function remained not significant. By contrast, a high proportion of falls, Alzheimer's disease, depression, cardiac failure and furosemide use

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ALZHEIMER'S DISEASE --- VITAMIN B6

Brain Nerve. 2007 Jul;59(7):731-7
[Disruption of amino acid metabolism in astrocyte and neurological disorders--possible implication of abnormal glia-neuron network in homocystineuria][Article in Japanese]
Enokido Y.
Department of Neuropathology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.

CBS is a vitamin B6-dependent transsulfuration enzyme needed to synthesize cysteine from methionine, catalyzing the condensation of serine with homocysteine to form cystathionine. A deficiency of CBS causes homocystinuria (MIM 236200), one of the most prevalent inborn errors, characterized by mental retardation, seizures, psychiatric disturbances, skeletal abnormalities and vascular disorders. Patients with CBS deficiency exhibit a major biochemical abnormality, hyperhomocysteinemia (HHcy), a condition associated with highly elevated plasma homocysteine levels. HHcy is recognized as a risk factor for several neurological diseases, such as cognitive impairment, dementia and Alzheimer's disease. Although the link between CBS deficiency and homocystinuria was first described over 40 years ago and mental retardation was the first clinical feature of the disease to be classified, very little is known about the role of CBS in the CNS. Here we show the regional and cellular distribution of CBS in the adult and developing mouse brain. In the adult mouse brain, CBS was expressed ubiquitously, but most intensely in the cerebellar molecular layer and hippocampal dentate gyrus. Immunohistochemical analysis revealed that CBS is preferentially expressed in cerebellar Bergmann glia and in astrocytes throughout the brain. At early developmental stages, CBS was expressed in neuroepithelial cells in the ventricular zone, but its expression changed to radial glial cells and then to astrocytes during the late embryonic and neonatal periods. Moreover, CBS was significantly accumulated in reactive astrocytes in the hippocampus after kainic acid-induced seizures, and cerebellar morphological abnormalities were observed in CBS-deficient mice. These results support the role of CBS in the development and maintenance of the CNS, and suggest that radial glia/astrocyte dysfunction might be involved in the complex neuropathological features associated with abnormal homocysteine metabolism.

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Nutr Hosp. 2007 Jan-Feb;22(1):7-24
Vitamin B6 status, deficiency and its consequences--an overview.
Spinneker A, Sola R, Lemmen V, Castillo MJ, Pietrzik K, Gonz�lez-Gross M.
Grupo Effects 262, Facultad de Medicina, Universidad de Granada, Spain.

BACKGROUND: Vitamin B6 is thought to be a most versatile coenzyme that participates in more than 100 biochemical reactions. It is involved in amino acid and homocysteine metabolism, glucose and lipid metabolism, neurotransmitter production and DNA/RNA synthesis. Vitamin B6 can also be a modulator of gene expression. Nowadays, clinically evident vitamin B6 deficiency is not a common disorder, at least in the general population. Nevertheless, a subclinical, undiagnosed deficiency may be present in some subjects, particularly in the elderly. OBJECTIVE: This review gives a complete overview over the metabolism and interactions of vitamin B6. Further, we show which complications and deficiency symptoms can occur due to a lack of vitamin B6 and possibilities for public health and supplemental interventions. METHODS: The database Medline (www.ncvi.nlm.nih.gov) was searched for terms like "vitamin B6", "pyridoxal", "cancer", "homocysteine", etc. For a complete understanding, we included studies with early findings from the forties as well as recent results from 2006. These studies were summarised and compared in different chapters. RESULTS AND CONCLUSION: In fact, it has been proposed that suboptimal vitamin B6 status is associated with certain diseases that particularly afflict the elderly population: impaired cognitive function, Alzheimer's disease, cardiovascular disease, and different types of cancer. Some of these problems may be related to the elevated homocysteine concentrations associated to vitamin B6 deficiency, but there is also evidence for other mechanisms independent of homocysteine by which a suboptimal vitamin B6 status could increase the risk for these chronic diseases.

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