A 44-month clinical-brain MRI follow-up in a patient with B
            <sub>12</sub>
            deficiency

Stojsavljević, Nebojša; Lević, Z; Drulović, Jelena; Dragutinović, G

doi:10.1212/wnl.49.3.878

Cited by 42 publications

(22 citation statements)

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“…Areas of demyelination on brain MRI have been described in vitamin B12-deficient patients or in those with diseases that affect vitamin B12 metabolism. [33][34][35] Thus, our findings lend support for the contention that poor vitamin B12 status is a risk factor for brain atrophy and possibly WMHV which in turn may contribute to cognitive impairment. The single MRI measure in the present study prevents direct investigation of whether poor vitamin B12 status results in cognitive decline by promoting faster rates of total brain atrophy or demyelination in selected white matter areas.…”

Section: Resultssupporting

confidence: 77%

Vitamin B12, cognition, and brain MRI measures: A cross-sectional examination

2011

Neurology

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Objective: To investigate the interrelations of serum vitamin B12 markers with brain volumes, cerebral infarcts, and performance in different cognitive domains in a biracial population sample cross-sectionally. Methods:In 121 community-dwelling participants of the Chicago Health and Aging Project, serum markers of vitamin B12 status were related to summary measures of neuropsychological tests of 5 cognitive domains and brain MRI measures obtained on average 4.6 years later among 121 older adults. Results:Concentrations of all vitamin B12-related markers, but not serum vitamin B12 itself, were associated with global cognitive function and with total brain volume. Methylmalonate levels were associated with poorer episodic memory and perceptual speed, and cystathionine and 2-methylcitrate with poorer episodic and semantic memory. Homocysteine concentrations were associated with decreased total brain volume. The homocysteine-global cognition effect was modified and no longer statistically significant with adjustment for white matter volume or cerebral infarcts. The methylmalonate-global cognition effect was modified and no longer significant with adjustment for total brain volume. Conclusions:Methylmalonate, a specific marker of B12 deficiency, may affect cognition by reducing total brain volume whereas the effect of homocysteine (nonspecific to vitamin B12 deficiency) on cognitive performance may be mediated through increased white matter hyperintensity and cerebral infarcts. Vitamin B12 status may affect the brain through multiple mechanisms. Neurology White matter hyperintensity volume (WMHV), cerebral infarcts, and total brain volume (TBV) have been related to performance in multiple cognitive domains 1-4 but few reports exist in which both cognitive performance and structural brain abnormalities are examined in the context of vitamin B12 status. 5,6 To date, no study has investigated these relations with vitamin B12 status among nonwhites or in populations with folic acid fortification policies such as in the United States.In our ongoing study of the risk factors for cognitive disorders in a biracial community, the Chicago Health and Aging Project (CHAP), we reported that brain MRI measures were associated with cognitive performance, especially perceptual speed in both blacks and whites. Moreover, we found that serum vitamin B12 and methylmalonic acid (MMA) concentrations were associated with 6-year cognitive decline.7 However, neither performance in specific cognitive domains nor brain MRI measures were examined in relation to vitamin B12-related markers in these reports. Thus, our primary objective in this study was to examine the relations of circulating levels of

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Section: Resultssupporting

confidence: 77%

Vitamin B12, cognition, and brain MRI measures: A cross-sectional examination

2011

Neurology

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“…Cobalamin levels below 100 pg/ml represent significant tissue deficiency of B 12 , and levels between 100 and 300 pg/ml justify testing for the metabolites homocysteine and methylmalonic acid, elevations of which also signify clinically relevant B 12 deficiency (Miller et al 2005). Well documented cases of dementia with MRI white matter lesions have demonstrated that treatment using parenteral vitamin B 12 improve both the dementia and the white matter changes (Chatterjee et al 1996;Stojsavljević et al 1997).…”

Section: Metabolic Disordersmentioning

confidence: 99%

White Matter: Organization and Functional Relevance

Filley

2010

Neuropsychol Rev

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Norman Geschwind's landmark paper in 1965, "Disconnexion Syndromes in Animals and Man," inspired a generation of investigators to consider the effects of focal brain lesions disrupting higher brain functions. Although Geschwind viewed disconnection as resulting from either white or gray matter lesions, his signature article drew upon the insights of 19th century neurologists and firmly established white matter within the vocabulary of behavioral neurology, neuropsychology, and cognitive neuroscience. This influence, and the advent of sensitive neuroimaging techniques later in the 20th century, led to white matter gradually gaining more attention as an essential component of distributed neural networks subserving cognition and emotion. Today, whereas focal white matter lesions remain central to the pathogenesis of classic neurobehavioral syndromes, diffuse white matter involvement is regarded as increasingly relevant to a wide variety of dementia syndromes and a host of neuropsychiatric disorders as well. In parallel, better understanding of the neurobiology of brain white matter at all ages has been achieved. While much remains to be explored, a general conceptual formulation is that white matter supports information transfer to complement the information processing carried out by gray matter. As knowledge of the organization and functional relevance of white matter continues to advance, improved understanding of the role of myelinated tracts in higher function can be anticipated, and with it many clinical benefits.

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“…223,224 A high prevalence of WMHs is also found in 22q11-deletion syndrome frequently associated with psychosis, 225 cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, which is caused by mutations in the NOTCH3 gene on chromosome 19 and frequently associated with depression, and other less common genetic conditions. [226][227][228][229] Nongenetic factors are associated with WMHs as well; [230][231][232][233][234][235][236][237][238] for example, Moore et al 239 reported a correlation between WMH and season of birth in a group of patients with BD. Thus, it appears that WMHs are not specific to BD and their usefulness as an endophenotype remains to be established.…”

Section: Basal Gangliamentioning

confidence: 99%

The phenotypes of bipolar disorder: relevance for genetic investigations

2005

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The search for susceptibility genes for bipolar disorder (BD) depends on appropriate definitions of the phenotype. In this paper, we review data on diagnosis and clinical features of BD that could be used in genetic studies to better characterize patients or to define homogeneous subgroups. Clinical symptoms, long-term course, comorbid conditions, and response to prophylactic treatment may define groups associated with more or less specific loci. One such group is characterized by symptoms of psychosis and linkage to 13q and 22q. A second group includes mainly bipolar II patients with comorbid panic disorder, rapid mood switching, and evidence of chromosome 18 linkage. A third group comprises typical BD with an episodic course and favourable response to lithium prophylaxis. Reproducibility of cognitive deficits across studies raises the possibility of using cognitive profiles as endophenotypes of BD, with deficits in verbal explicit memory and executive function commonly reported. Brain imaging provides a more ambiguous data set consistent with heterogeneity of the illness. Keywords: bipolar disorder; genetics; endophenotype; neurocognitive function; brain imaging Bipolar disorder (BD) has a genetic basis with heritability of at least 80%. 1 A number of studies have attempted to map the susceptibility loci giving evidence of linkage in multiple genomic regions. In particular, findings in 4p, 4q, 8q, 10p, 12q24, 13q, 18p, 18q, 21q, and 22q have been supported by more than one study. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] However, these studies have not identified any specific genes, and a recent metaanalysis of available genome scans showed no regions with a conclusive evidence of linkage. 20 The relatively slow progress of gene-mapping efforts is often explained by the 'complex' nature of the illness and of the genotype-phenotype relation. The complexity most likely includes heterogeneity, interactions of multiple loci, incomplete penetrance, as well as phenotypes resulting from environmental effects-either alone or in interaction with the genetic predisposition. The goal of psychiatric genetic research is identification of (heritable) variations in DNA sequence or function that influence behaviour or give rise to mental illness. By definition, in complex (multifactorial) traits, this link is not unique and specific. That is, a particular change in gene sequence does not necessarily lead to a specific behaviour, and similar behaviours (symptoms) may be due to distinct (sets of) genes. Moreover, we must consider the possibility that the path between the genotype and behaviour is not unidirectional. Emerging examples point not only to general effects of environment, for instance stress, on behaviour, but also to specific behaviours influencing gene function that can be transmitted onto the next generation. 21 No single method is considered clearly superior in identifying susceptibility genes for complex traits such as BD. Most researchers agree that a combination of strategies is most lik...

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A 44-month clinical-brain MRI follow-up in a patient with B ₁₂ deficiency

Cited by 42 publications

References 3 publications

Vitamin B12, cognition, and brain MRI measures: A cross-sectional examination

Vitamin B12, cognition, and brain MRI measures: A cross-sectional examination

White Matter: Organization and Functional Relevance

The phenotypes of bipolar disorder: relevance for genetic investigations

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A 44-month clinical-brain MRI follow-up in a patient with B 12 deficiency

Cited by 42 publications

References 3 publications

Vitamin B12, cognition, and brain MRI measures: A cross-sectional examination

Vitamin B12, cognition, and brain MRI measures: A cross-sectional examination

White Matter: Organization and Functional Relevance

The phenotypes of bipolar disorder: relevance for genetic investigations

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A 44-month clinical-brain MRI follow-up in a patient with B ₁₂ deficiency