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Title:   Author  item
                                            Garrod, Marjorieitem
                                            GREEN, RALPH - UCDMC, MED. PATHOLOGYitem
                                            Allen, Lindsay

                                                         - *A*item
                                            MUNGAS, DAN - UCD NEUROLOGYitem
                                            JAGUST, WILLIAM - UNIV. BERKELEY,NEURO INSTitem
                                            HAAN, MARY - UNIV.MICHIGAN,EPIDEMIOLOGitem
                                            MILLER, JOSHUA - UCDMC
  Submitted to: Clinical Chemistry
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 3/18/2008
                                    Publication  Date: 7/1/2008
                                    Citation: Garrod, M.G., Green, R., Allen, L.H., Mungas, D.M., Jagust, W.J., Haan, M.N., Miller, J.W. 2008. THE FRACTION OF TOTAL PLASMA VITAMIN B12 BOUND TO TRANSCOBALAMIN CORRELATES WITH COGNITIVE FUNCTION IN ELDERLY LATINOS WITH DEPRESSIVE SYMPTOMS. Clinical Chemistry.  54:7, 1210-1217, 2008.Interpretive Summary: Only the 20-30% of the plasma vitamin B-12 is in the form of holotranscobalamin (holoTC). HoloTC is considered to be the only fraction of total plasma B12 that delivers the vitamin to cells, but there is little information on the associations between holoTC concentrations and various clinical and functional outcomes. The association between holoTC, as well as total plasma B-12 and the holoTC/B12 ratio, was assessed in 1089 elderly (age 60-101 years) Latinos living in Sacramento, CA. The holoTC/B12 ratio was associated with cognitive function (Mini-Mental State Examination 3MSE score) but not with a delayed recall test. Elderly who had more depressive symptoms (scoring 16 or more on the Center for Epidemiological Studies Depression Scale) and were in the lowest third of holoTC/B12 ratio values were 3.6 times more likely to have clinical cognitive impairment than those in the highest third of holoTC/B12 ratios.  HoloTC was also correlated with the 3MSE score. There were no associations between cognitive function and total plasma B12. The holoTC/B12 ratio may be a better reflection of vitamin B12 adequacy for nervous system function than either total plasma B12 or holoTC alone.
                                Technical Abstract: Background: The fraction of total plasma vitamin B12 bound to transcobalamin (holoTC/B12 ratio) may reflect tissue levels of the vitamin, but its clinical relevance is unclear. 
Methods: associations between cognitive function and total B12, holoTC, and holoTC/B12 ratio were assessed in a cohort of elderly Latinos (n=1089; age 60–101y). Cognitive function was assessed using the modified mini-mental state examination (3MSE) and a delayed recall test; clinical cognitive impairment was diagnosed by neuropsychological and clinical exam with expert adjudication; and depressive symptoms were assessed using the Center for
Epidemiological Studies Depression Scale (CES-D). Total B12 was measured by radioassay and holoTC by antibody assay.
Results: HoloTC/B12 ratio was directly associated with 3MSE score (p=0.026), but not delayed recall score. Interactions between holoTC/B12 ratio and CES-D score were observed for 3MSE (p=0.026) and delayed recall scores (p=0.013) such that associations between the ratio and cognitive function scores were confined to subjects with CES-D =16. For subjects with CES-D =16, the odds ratio for clinical cognitive impairment for the lowest holoTC/B12 ratio tertile was 3.6 (1.2, 11.2) compared with the highest tertile (p=0.03). No associations were observed between cognitive function and total B12 or holoTC alone except between holoTC and 3MSE
score (p=0.021). No interactions between holoTC or total B12 and CES-D score on cognitive function were observed.
Conclusions: HoloTC/B12 ratio is associated with cognitive function in elderly Latinos with depressive symptoms, and may better reflect the adequacy of B12 for nervous system function
than either holoTC or total B12 alone.


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