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2 Nutritional Biochemistry Laboratory, Human Adaptation and Countermeasures Office, NASA Lyndon B. Johnson Space Center, Houston, TX 77058; 3 Enterprise Advisory Services, Inc., Houston, TX 77058; 4 Universities Space Research Association, Houston, TX 77058; 5 Consortium for Research in Elder Self-Neglect of Texas (CREST), Quentin Mease Hospital, Baylor College of Medicine, Houston, TX 77058; and 6 Sealy Center on Aging, University of Texas Medical Branch at Galveston, Galveston, TX 77555
* To whom correspondence should be addressed. E-mail: scott.m.smith{at}nasa.gov.
| ABSTRACT |
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-tocopherol were lower in SN subjects (0.28 ± 0.2 vs. 0.43 ± 0.33 µmol/L; 23.2 ± 9.3 vs. 27.8 ± 9.3 µmol/L, P < 0.05). SN subjects had a lower serum concentration of 25-hydroxyvitamin D than CN subjects (33.7 ± 16.4 vs. 44.1 ± 19.6 nmol/L, P < 0.05). These differences in markers of nutritional status show that the self-neglecting elderly are at risk for altered nutritional status, particularly of folate, antioxidants, and vitamin D. Evaluation of these data in relation to other functional and cognitive assessments are critical for evaluating the relation between nutrition and self-neglect.
| Introduction |
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Elder self-neglect is a phenomenon that encompasses a wide range of social, health, and housing issues. For risk factors to predict whether elder self-neglect can be determined, the condition itself must be better characterized in terms of these issues. Considerable evidence shows that the status of certain nutrients is related to some of the cognitive effects associated with self-neglect (37). For example, in community-based elderly populations with good health, adequate folate status is associated with higher cognitive function scores and is inversely associated with dementia (68). Elderly individuals commonly have lower blood concentrations of other nutrients, such as vitamin D, vitamin B-6, and vitamin B-12, than younger individuals, but it is not well understood whether the status of these and other nutrients is exacerbated by self-neglect (3,911).
Goodwin et al. (12) were the first to report that healthy elderly subjects who had low blood concentrations or intakes of folate, vitamin B-12, vitamin C, and riboflavin scored poorly on tests of memory and nonverbal abstract thinking. Several studies reported improvement in cognitive function after supplementation with these vitamins (1317). The role of B vitamins in homocysteine metabolism is fundamentally important, and may contribute to the mechanisms of altered cognitive function. Homocysteine is a sulfur-containing amino acid formed from the de-methylation of methionine. It is metabolized through 2 pathways, remethylation and transsulfuration, which require folate, vitamin B-6, and vitamin B-12 as cofactors. The literature is replete with data showing that elevated plasma total homocysteine is a risk factor for dementia, Alzheimer's disease, and other cognitive problems in the elderly (8,1821).
In the present study, we considered the possibility that elderly persons exhibiting self-neglect characteristics may have underlying nutrient deficiencies that could be identified as risk factors for the condition. These findings are part of a larger effort, the Consortium for Research in Elder Self-Neglect of Texas (CREST).7 The initial CREST project was designed to characterize individuals suffering from self-neglect. This article is a report of the initial findings with regard to nutritional assessment.
| Subjects and Methods |
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Subjects. Self-neglect (SN) subjects were recruited from individuals referred by the Adult Protective Services (APS) program of the Texas Department of Family and Protective Services. Once APS determined that one of their clients was a potential candidate for inclusion in the study, they obtained written permission from the client to refer the client's name to the CREST project. Upon receiving a client referral from APS, the CREST research field team, consisting of 2 research coordinators, visited the client at home and obtained the client's written consent to participate in the study. In instances when a subject's mental capacity to participate was uncertain, the research coordinator asked the subject to state the purpose of the study and to recite the risks and benefits of participation.
Self-neglectors were matched for age, gender, ethnicity, and socio-economic status to nonself-neglecting control (CN) subjects recruited from Baylor College of Medicine's geriatrics program at the Harris County Hospital District in Houston, Texas. Patients seen in the geriatrics program are generally frail elders who have impaired cognition or mobility problems and complex social issues, including poverty. The parameter used to match for age was the SN subject's age ± 2 y. To match for socio-economic status, the list of all 5-digit zip codes within the city of Houston was divided into deciles by median income, and a CN subject was recruited from any zip code within the same decile as the SN subject's zip code. A further requirement was that a CN subject had no history of validated self-neglect on record with APS. All SN and CN subjects were community-dwelling participants in an urban setting and all resided in Houston.
The informed consent procedure and data collection were conducted in each SN and CN subject's home to increase the subject's ease and comfort and minimize loss of follow-up due to lack of transportation or frailty. Reported here are data on 40 SN subjects (16 M, 24 F; age 76 ± 7 y; body weight 78 ± 27 kg) and 40 CN subjects (14 M, 26 F; 76 ± 7 y, 80 ± 23 kg). Ethnicity of the groups was divided as follows: SN: 52.5% black, 40% white, and 7.5% Hispanic; CN: 67.5% black and 32.5% white. There were no differences between groups with regard to marital status, income, or education level. SN subjects had fewer prescription medications than controls and tended to be more likely to live alone (see Table 1 for more detail on subject characteristics).
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Anthropometrics. The research coordinator used a scale and stadiometer to obtain body weight and height from individuals during their interview.
Biological sample collection and processing.
Blood samples were collected from all study participants at the end of the home visit. A total of
37.7 mL of blood was collected from each subject for all tests described here. Blood samples were collected into appropriate tubes (including mineral-free tubes for the mineral analyses). Whole blood analyses were performed immediately with a portable analyzer (22), and, as soon (not >30 min) as samples were returned to the Harris County Hospital District's clinical laboratory at Quentin Mease Hospital (the CREST lab), analyses were performed with the clinical hematology analyzer Sysmex XT-1800i (Dade Behring). Other samples were placed on ice until they were transported back to the CREST lab for further processing to yield red blood cells, plasma, or serum, depending on the specific analyte to be measured. Aliquots were stored frozen at 70°C, and were delivered about twice per month to the Johnson Space Center for the remaining analyses.
Biochemical analyses. The testing profile used here was a modification of the nutritional status assessment profile that we used in other clinical and research settings (i.e., the profile performed on astronauts before and after long-duration space missions) (23). With few exceptions, all biochemical analyses were performed at the Johnson Space Center by trained personnel. Most analyses were performed by standard commercial techniques, as described previously (2325). Serum ferritin and transferrin were analyzed using the Immulite (Diagnostic Products) and Array 360 (Beckman Coulter) instruments, respectively. Transferrin receptors were measured using a commercially available ELISA (Ramco Laboratories). Red blood cell folate and serum vitamin B-12 were measured using a commercially available radioreceptor assay (Diagnostic Products). Ferritin iron content was determined by inductively coupled plasma mass spectrometry (ICP-MS) as previously described (24). The pH and concentrations of electrolytes, glucose, and ionized calcium in whole blood were determined at subjects' homes with a portable analyzer (i-STAT) (22,24,26).
Serum total calcium, iron, zinc, and copper concentrations were measured by ICP-MS (27). Serum intact parathyroid hormone (PTH) was measured by immunoradiometric assay (Nichols Institute Diagnostics). The vitamin D metabolites, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, were determined using commercially available RIA kits (DiaSorin). Bone-specific alkaline phosphatase (BSAP) was measured by ELISA (Quidel), and serum osteocalcin was measured by a commercial RIA kit (Biomedical Technologies).
Serum samples were analyzed for the collagen crosslink N-telopeptide (NTx) using a commercially available kit (Osteomark NTX ELISA kit, Inverness Laboratories).
Red blood cell superoxide dismutase (SOD), glutathione peroxidase (GPX), and total antioxidant capacity (TAC) were measured spectrophotometrically using commercially available kits (Randox Laboratories).
Serum total cholesterol, triglycerides, albumin, sodium, potassium, chloride, creatinine, alanine transaminase (ALT), aspartate transaminase (AST), and total alkaline phosphatase were assayed using an Olympus AU400E automated clinical chemistry system (Olympus), and CRP was analyzed with the Immulite 2000 (Diagnostic Products). Serum protein electrophoresis was performed with the Beckman Appraise (Beckman Coulter). Retinol-binding protein (RBP) was measured using a radial immunodiffusion kit (The Binding Site).
Fat-soluble vitamins were analyzed in plasma by HPLC with electrochemical detection (28). We used a chromatographic system from ESA Biosciences consisting of 2 model 582 pumps, a high-pressure gradient mixer, a model 540 autosampler with a refrigerated sample tray, a CoulArray thermostatic chamber, and a model 5600 CoulArray 8-channel system to separate, detect, and quantify fat-soluble vitamins. The separation of fat-soluble vitamins was carried out on a C18 column (MD-150, 150 x 3.0 mm, 3 µm, ESA) using a methanol/1-propanol/ammonium acetate binary gradient with a flow rate of 0.8 mL/min. Both external and internal standard calibration curves were used for quantification. This method was linear for all analytes over their physiological range.
Methylmalonic acid (MMA), total homocysteine, cystathionine, and 2-methylcitric acid were determined in serum by GC-MS in an external commercial laboratory (Metabolite Laboratories).
Statistical analysis. Statistical analyses were designed to test the hypothesis that the nutritional status of self-neglect subjects was different from that of control subjects, and that nutritional status of females was different from that of males. This was accomplished using a 2-way factorial design and evaluating data using 2-way ANOVA (group, gender, group x gender interaction). Statistical analyses were performed with the data either in their original metric or transformed to a square root or natural logarithm scale to achieve acceptable distributional normality and homogeneity of variance as determined by the Kolmogorov-Smirnov normality test. Normalization was required for MMA, total homocysteine, cystathionine, 2-methylcitric acid, RBC folate, serum folate, vitamin B-12, C-reactive protein, ß-carotene, PTH, BSAP, osteocalcin, NTx, copper, iron, transferrin receptors, retinol-binding protein, ALT, AST, alkaline phosphatase, transferrin, ferritin, and creatinine.
The general linear model (GLM) was used to analyze the data. When analysis indicated the existence of outliers (data points exhibiting a standard GLM residual of
3.0), the data were then reanalyzed without the outliers. The number of outliers that manifested for each test are noted in the table footnotes.
When significant differences were found between SN and CN groups or genders, the Pearson correlation coefficient between the analyte and body weight was computed to assess whether a confounding effect of body weight was present. When a significant interaction between group and gender was noted, a post-hoc Bonferroni test was used to determine pairwise differences within groups and within genders.
Statistical analyses were performed using Minitab version 14 statistical software. Values are expressed as means ± SD, and significance was assigned at P < 0.05.
| Results |
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The triglyceride concentration of SN subjects was lower than that of CN subjects (Table 2). The Pearson correlation between triglyceride concentration and body weight was significant for SN (but not CN) subjects (P = 0.02) (Fig. 2). For both SN and CN subjects, no correlation was found between the amount of time since the last meal and serum triglyceride.
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Oxidative damage markers and antioxidants. RBC SOD was lower in SN subjects than in CN subjects. TAC of the 2 groups did not differ, but males had a higher TAC than females (P < 0.05). Whole blood GPX activity was not affected by group or gender GPX (Table 3).
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-tocopherol concentration was lower in SN subjects than in CN subjects, but there was no gender difference. An interaction between group and gender occurred for coenzyme Q10, but no difference was seen between groups or genders for
-tocopherol (Table 4). Only one subject (SN male) had elevated plasma retinyl palmitate (0.334 µmol/L).
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The serum parathyroid hormone concentration tended to be higher in SN subjects (P = 0.09) (Table 6). In the original statistical analysis, 3 CN outliers were removed (as noted in Table 6 footnote). Several subjects (5 SN, 3 CN) with elevated PTH concentrations (>100 nmol/L) were not identified as outliers. Removal of these additional points did not change findings (SN tended to be higher than CN, P = 0.08), but the variability in the data were reduced: SN males, 46 ± 15; SN females, 47 ± 22; CN males, 37 ± 21; CN females, 38 ± 21 nmol/L.
Serum minerals. Serum zinc, copper, and selenium concentrations did not differ between groups (data not shown). Males had a lower concentration of copper (P < 0.05), and tended to have a higher serum concentration of selenium (P = 0.09) than females.
| Discussion |
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Homocysteine is a known neurotoxin (31,32), and evidence exists that it is involved in cardiovascular disease (33,34). Whether a high serum homocysteine concentration is a cause or an effect of disease is a point of controversy (5,35,36), but for the self-neglectors in this study, the high serum homocysteine may be related to one or more nutrient deficiencies, given its association with elevated MMA. In addition to the neurotoxic effect of homocysteine that accompanies a folate deficiency, other mechanisms potentially relating folate deficiency to elder self-neglect include decreased methylation reactions in the central nervous system. These reactions are needed for proper myelination of neurons, synthesis of neurotransmitters and membrane phospholipids, and DNA methylation.
Besides nutrient deficiencies, another possible explanation for the higher blood concentration of homocysteine in SN subjects may be the likelihood that certain drugs can alter homocysteine concentrations by interfering with folate, vitamin B-12, or vitamin B-6 metabolism, or by altering renal function. Some drugs known to increase plasma homocysteine concentration include lipid-lowering drugs (such as fibrates and niacin) and oral hypoglycemic drugs (e.g., metformin), insulin, and drugs used to treat arthritis or epilepsy (3741).
Although genetic factors were not investigated in the present study, plasma homocysteine is influenced by genetics (33,42). In situations where folate intake is low, the 5,10-methylenetetrahydrofolate reductase (MTHFR) C(677)T polymorphism is associated with elevated plasma homocysteine concentrations (42,43). Furthermore, several studies showed that individuals who had this polymorphism along with low folate status had decreased cognitive performance (4446). Further research is needed to determine whether a relation exists between self-neglect and genetics as it pertains to folate metabolism.
It is likely that several mechanisms can explain the neurological consequences of self-neglect, and more research is needed to determine whether elevated plasma homocysteine or low nutrient status is a cause or effect of the condition. A limitation of this study is that the cross-sectional design precludes determination of cause and effect. The data do, however, provide strong evidence that self-neglectors are in a state of compromised nutritional status.
The difference in fat-soluble vitamin status between SN and CN subjects is somewhat striking, and may help to substantiate a causal relation between self-neglect and nutrition. The role of vitamins A and E as antioxidants has been well established, as have the effects of these antioxidants on the aging process (47). The lower plasma concentrations in the SN group of certain antioxidants, as well as the lower concentrations of RBC superoxide dismutase and retinol-binding protein, suggest that these individuals may be at increased risk for oxidative stress, development and advancement of cataracts (48,49), and changes in mental status (50).
Vitamin D has received much attention in recent years due to the re-emergence of vitamin-D deficiency as a public health concern, especially for the elderly (51,52). The findings here validate this concern, insofar as a large percentage of both SN and CN groups had very low vitamin D stores. The metabolic effects of vitamin-D deficiency were clear: of 16 subjects (10 SN, and 6 CN) who had 25-hydroxyvitamin D levels <25 nmol/L, 13 of them had above-mean serum NTx (bone resorption marker). Presumably, self-neglectors do not get out in the sun often. The fact that the data presented here are from subjects whose blood samples were collected April through October, and who lived in the sun-belt city of Houston, shows that vitamin D is not an issue for northerners only.
The image most often conjured by self-neglect is of frail, thin, elderly persons, but the subjects reported here were generally not petite. Although we documented many specific nutrient deficits, these appear to be related to poor food choices, rather than to general undernutrition. Moreover, the fact that SN and CN groups did not differ in the values of many variables (e.g., hematology and clinical chemistry variables, and proteins) is further evidence that this is not a situation of general malnutrition, as might be expected, but of an as-yet-unknown set of contributing factors that may have led to specific nutrient deficiencies.
The question that arises quite naturally, given a subject population such as the one included in this study is, What was the prevalence of multiple deficiencies? To answer this question, we determined the number of subjects with abnormal results for homocysteine (high), 25-hydroxyvitamin D (low),
-tocopherol (low), and retinol (low) (Fig. 3). Our answer is puzzling: although the incidence of multiple deficiencies was greater in the SN subjects, the proportion of subjects from either the SN or CN group who had multiple deficiencies was by no means overwhelming. The lack of a common finding may complicate the generalization of nutritional deficiencies in self-neglectors.
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This study was designed to characterize the self-neglecting elderly, and to document their nutritional status. The data clearly indicate that nutritional deficiencies are a critical issue for the self-neglecting elderly and, specifically, that they are at risk for deficiencies of folate, vitamin B-12, antioxidants, and vitamin D. These data are particularly striking when one considers that the control group was composed of elderly public hospital outpatients rather than healthy, community-dwelling seniors. An evaluation of these data in relation to other functional and cognitive assessments of self-neglectors is crucial for evaluating the relation between nutrition and self-neglect. Of the many questions that arise from this research, the 2 that are, in our view, the most obvious and most critical are these: 1) Are nutritional deficiencies a cause of self-neglect, or a consequence? and 2) Can these deficiencies be corrected and, if so, will that enable a return to self-reliance?
| ACKNOWLEDGMENTS |
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| FOOTNOTES |
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7 Abbreviations used: ALT, alanine transaminase; AST, aspartate transaminase; APS, Adult Protective Services; BSAP, bone-specific alkaline phosphatase; CN, control group; CREST, Consortium for Research in Elder Self-Neglect of Texas; CRP, C-reactive protein; GPX, glutathione peroxidase; ICP-MS, inductively coupled plasma mass spectrometry; MMA, methylmalonic acid; NTx, N-telopeptide; PTH, parathyroid hormone; SN, self-neglectors; SOD, superoxide dismutase; TAC, total antioxidant capacity. ![]()
Manuscript received 31 March 2006. Initial review completed 13 May 2006. Revision accepted 17 July 2006.
| LITERATURE CITED |
|---|
|
|
|---|
1. Lauder W, Davidson G, Anderson I, Barclay A. Self-neglect: the role of judgements and applied ethics. Nurs Stand. 2005;19:4551; quiz 52, 54.[Medline]
2. Teaster PB, Dugar TA, Mendiondo MS, Abner EL, Cecil KA, Otto JM. The 2004 survey of state adult protective services: abuse of adults 60 years of age and older [monograph on the Internet]. Washington: National Center on Elder Abuse; 2006 [cited 2006 Aug 11]. Available from: http://www.elderabusecenter.org/pdf/2-14-06%20FINAL%2060+REPORT.pdf.
3. Nilsson-Ehle H. Age-related changes in cobalamin (vitamin B-12) handling. Implications for therapy. Drugs Aging. 1998;12:27792.[Medline]
4. Bottiglieri T. Homocysteine and folate metabolism in depression. Prog Neuropsychopharmacol Biol Psychiatry. 2005;29:110312.[Medline]
5. Selhub J, Bagley LC, Miller J, Rosenberg IH. B vitamins, homocysteine, and neurocognitive function in the elderly. Am J Clin Nutr. 2000;71:614S20S.
6. Ramos MI, Allen LH, Haan MN, Green R, Miller JW. Plasma folate concentrations are associated with depressive symptoms in elderly Latina women despite folic acid fortification. Am J Clin Nutr. 2004;80:10248.
7. Ramos MI, Allen LH, Mungas DM, Jagust WJ, Haan MN, Green R, Miller JW. Low folate status is associated with impaired cognitive function and dementia in the Sacramento area Latino study on aging. Am J Clin Nutr. 2005;82:134652.
8. Ravaglia G, Forti P, Maioli F, Martelli M, Servadei L, Brunetti N, Porcellini E, Licastro F. Homocysteine and folate as risk factors for dementia and Alzheimer disease. Am J Clin Nutr. 2005;82:63643.
9. Krall EA, Sahyoun N, Tannenbaum S, Dallal GE, Dawson-Hughes B. Effect of vitamin D intake on seasonal variations in parathyroid hormone secretion in postmenopausal women. N Engl J Med. 1989;321:177783.[Abstract]
10. Tolonen M, Schrijver J, Westermarck T, Halme M, Tuominen SE, Frilander A, Keinonen M, Sarna S. Vitamin B6 status of Finnish elderly. Comparison with Dutch younger adults and elderly. The effect of supplementation. Int J Vitam Nutr Res. 1988;58:737.[Medline]
11. Chen LH, Fan-Chiang WL. Biochemical evaluation of riboflavin and vitamin B6 status of institutionalized and non-institutionalized elderly in central Kentucky. Int J Vitam Nutr Res. 1981;51:2328.[Medline]
12. Goodwin JS, Goodwin JM, Garry PJ. Association between nutritional status and cognitive functioning in a healthy elderly population. JAMA. 1983;249:291721.
13. Deijen JB, van der Beek EJ, Orlebeke JF, van den Berg H. Vitamin B-6 supplementation in elderly men: effects on mood, memory, performance and mental effort. Psychopharmacology (Berl). 1992;109:48996.[Medline]
14. Martin DC, Francis J, Protetch J, Huff FJ. Time dependency of cognitive recovery with cobalamin replacement: report of a pilot study. J Am Geriatr Soc. 1992;40:16872.[Medline]
15. Wouters-Wesseling W, Wagenaar LW, Rozendaal M, Deijen JB, de Groot LC, Bindels JG, van Staveren WA. Effect of an enriched drink on cognitive function in frail elderly persons. J Gerontol A Biol Sci Med Sci. 2005;60:26570.
16. Sram RJ, Binkova B, Topinka J, Kotesovec F, Fojtikova I, Hanel I, Klaschka J, Kocisova J, Prosek M, Machalek J. Effect of antioxidant supplementation in an elderly population. Basic Life Sci. 1993;61:45977.[Medline]
17. Masaki KH, Losonczy KG, Izmirlian G, Foley DJ, Ross GW, Petrovitch H, Havlik R, White LR. Association of vitamin E and C supplement use with cognitive function and dementia in elderly men. Neurology. 2000;54:126572.
18. Tucker KL, Qiao N, Scott T, Rosenberg I, Spiro, 3rd A. High homocysteine and low B vitamins predict cognitive decline in aging men: the veterans affairs normative aging study. Am J Clin Nutr. 2005;82:62735.
19. Bell IR, Edman JS, Selhub J, Morrow FD, Marby DW, Kayne HL, Cole JO. Plasma homocysteine in vascular disease and in nonvascular dementia of depressed elderly people. Acta Psychiatr Scand. 1992;86:38690.[Medline]
20. McCaddon A, Davies G, Hudson P, Tandy S, Cattell H. Total serum homocysteine in senile dementia of Alzheimer type. Int J Geriatr Psychiatry. 1998;13:2359.[Medline]
21. Lehmann M, Gottfries CG, Regland B. Identification of cognitive impairment in the elderly: homocysteine is an early marker. Dement Geriatr Cogn Disord. 1999;10:1220.[Medline]
22. Smith SM, Davis-Street JE, Fontenot TB, Lane HW. Assessment of a portable clinical blood analyzer during space flight. Clin Chem. 1997;43:105665.
23. Smith SM, Zwart SR, Block G, Rice BL, Davis-Street JE. Nutritional status assessment of international space station crew members. J Nutr. 2005;135:43743.
24. Smith SM, Davis-Street JE, Rice BL, Nillen JL, Gillman PL, Block G. Nutritional status assessment in semiclosed environments: ground-based and space flight studies in humans. J Nutr. 2001;131:205361.
25. Smith SM, Davis-Street JE, Fesperman JV, Smith MD, Rice BL, Zwart SR. Nutritional assessment during a 14-d saturation dive: the NASA extreme environment mission operations V project. J Nutr. 2004;134:176571.
26. Smith MD, Davis-Street JE, Calkins DS, Nillen JL, Smith SM. Stability of i-Stat EC6+ cartridges: effect of storage temperature on shelf life. Clin Chem. 2004;50:66973.
27. Hsiung CS, Andrade JD, Costa R, Ash KO. Minimizing interferences in the quantitative multielement analysis of trace elements in biological fluids by inductively coupled plasma mass spectrometry. Clin Chem. 1997;43:230311.
28. ESA Biosciences I. Simultaneous analysis of carotenoidsretinoids, tocopherols, vitamin K1 and coenzyme Q10 in plasma. Chelmsford, MA: ESA Biosciences; 1996. Report No.: Technical brief 101176F.
29. Harris SS. Vitamin D and African Americans. J Nutr. 2006;136:11269.
30. Abrams RC, Lachs M, McAvay G, Keohane DJ, Bruce ML. Predictors of self-neglect in community-dwelling elders. Am J Psychiatry. 2002;159:172430.
31. Lipton SA, Kim WK, Choi YB, Kumar S, D'Emilia DM, Rayudu PV, Arnelle DR, Stamler JS. Neurotoxicity associated with dual actions of homocysteine at the N-methyl-D-aspartate receptor. Proc Natl Acad Sci USA. 1997;94:59238.
32. Kruman II, Kumaravel TS, Lohani A, Pedersen WA, Cutler RG, Kruman Y, Haughey N, Lee J, Evans M, Mattson MP. Folic acid deficiency and homocysteine impair DNA repair in hippocampal neurons and sensitize them to amyloid toxicity in experimental models of Alzheimer's disease. J Neurosci. 2002;22:175262.
33. Chu NF. Plasma hyperhomocysteinemia, MTHFR polymorphism and thromboembolic disease: an example of gene-nutrition interactions in chronic disease. J Chin Med Assoc. 2005;68:5579.[Medline]
34. Undas A, Brozek J, Szczeklik A. Homocysteine and thrombosis: from basic science to clinical evidence. Thromb Haemost. 2005;94:90715.[Medline]
35. Marcucci R, Gori AM, Abbate R. Hyperhomocysteinemia: cause or effect of disease? Blood. 2005;105:33823; author reply 34.
36. Shai I, Stampfer MJ, Ma J, Manson JE, Hankinson SE, Cannuscio C, Selhub J, Curhan G, Rimm EB. Homocysteine as a risk factor for coronary heart diseases and its association with inflammatory biomarkers, lipids and dietary factors. Atherosclerosis. 2004;177:37581.[Medline]
37. Dierkes J, Westphal S. Effect of drugs on homocysteine concentrations. Semin Vasc Med. 2005;5:12439.[Medline]
38. Dierkes J, Westphal S, Luley C. Fenofibrate-induced hyperhomocysteinaemia: clinical implications and management. Drug Saf. 2003;26:8191.[Medline]
39. Dierkes J, Westphal S, Luley C. The effect of fibrates and other lipid-lowering drugs on plasma homocysteine levels. Expert Opin Drug Saf. 2004;3:10111.[Medline]
40. Westphal S, Rading A, Luley C, Dierkes J. Antihypertensive treatment and homocysteine concentrations. Metabolism. 2003;52:2613.[Medline]
41. Huemer M, Ausserer B, Graninger G, Hubmann M, Huemer C, Schlachter K, Tscharre A, Ulmer H, Simma B. Hyperhomocysteinemia in children treated with antiepileptic drugs is normalized by folic acid supplementation. Epilepsia. 2005;46:167783.[Medline]
42. Gellekink H, den Heijer M, Heil SG, Blom HJ. Genetic determinants of plasma total homocysteine. Semin Vasc Med. 2005;5:98109.[Medline]
43. Cravo M. Alcohol, methylenetetrahydrofolate 677C->T genotype, and low folate intake: concurrent causes for hyperhomocysteinemia. Am J Clin Nutr. 2005;82:34.
44. Durga J, van Boxtel MP, Schouten EG, Bots ML, Kok FJ, Verhoef P. Folate and the methylenetetrahydrofolate reductase 677C
T mutation correlate with cognitive performance. Neurobiol Aging. 2006;27:33443.[Medline]
45. Kelly CB, McDonnell AP, Johnston TG, Mulholland C, Cooper SJ, McMaster D, Evans A, Whitehead AS. The MTHFR C677T polymorphism is associated with depressive episodes in patients from Northern Ireland. J Psychopharmacol. 2004;18:56771.
46. Calvaresi E, Bryan J. B vitamins, cognition, and aging: a review. J Gerontol B Psychol Sci Soc Sci. 2001;56:P32739.
47. Mayne S. Antioxidant nutrients and chronic disease: use of biomarkers of exposure and oxidative status in epidemiologic research. J Nutr. 2003;133:933S40S.
48. Knekt P, Heliovaara M, Rissanen A, Aromaa A, Aaran RK. Serum antioxidant vitamins and risk of cataract. BMJ. 1992;305:13924.
49. Varma SD, Devamanoharan PS, Morris SM. Prevention of cataracts by nutritional and metabolic antioxidants. Crit Rev Food Sci Nutr. 1995;35:11129.[Medline]
50. Cherubini A, Martin A, Andres-Lacueva C, Di Iorio A, Lamponi M, Mecocci P, Bartali B, Corsi A, Senin U, Ferrucci L. Vitamin E levels, cognitive impairment and dementia in older persons: the InCHIANTI study. Neurobiol Aging. 2005;26:98794.[Medline]
51. Dawson-Hughes B. Racial/ethnic considerations in making recommendations for vitamin D for adult and elderly men and women. Am J Clin Nutr. 2004;80:1763S6S.
52. Gennari C. Calcium and vitamin D nutrition and bone disease of the elderly. Public Health Nutr. 2001;4:54759.[Medline]
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