Plasma vitamin B12 status and cerebral white-matter lesions.
OBJECTIVE
Elevated homocysteine has been associated with a higher prevalence of cerebral white-matter lesions and infarcts, and worse cognitive performance. This raises the question whether factors involved in homocysteine metabolism, such as vitamin B(12), are also related to these outcomes. This study examined the association of several markers of vitamin B(12) status with cerebral white-matter lesions, infarcts and cognition.


METHODS
The study evaluated the association of plasma concentrations of vitamin B(12), methylmalonic acid, holotranscobalamin and transcobalamin saturation with cerebral white-matter lesions and infarcts at baseline and cognition at baseline and during follow-up among 1019 non-demented elderly participants of the population-based Rotterdam Scan Study. Analyses were adjusted for several potential confounders, including homocysteine and folate concentration.


RESULTS
Poorer vitamin B(12) status was significantly associated with greater severity of white-matter lesions, in particular periventricular white-matter lesions, in a concentration-related manner. Adjustment for common vascular risk factors (including blood pressure, smoking, diabetes and intima media thickness) did not alter the associations. Adjustment for homocysteine and folate modestly weakened the associations. No association was observed for any of the studied markers of vitamin B(12) status with presence of brain infarcts and baseline cognition or cognitive decline during follow-up.


CONCLUSIONS
These results indicate that vitamin B(12) status in the normal range is associated with severity of white-matter lesions, especially periventricular lesions. Given the absence of an association with cerebral infarcts, it is hypothesised that this association is explained by effects on myelin integrity in the brain rather than through vascular mechanisms.
de Lau
L M L
LM
Department of Epidemiology and Biostatistics, Erasmus Medical Centre, Rotterdam, The Netherlands.
Smith
A D
AD
Refsum
H
H
Johnston
C
C
Breteler
M M B
MM
D000368:Aged; D015415:Biomarkers; D001921:Brain / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D002544:Cerebral Infarction / Q000097:blood* / Q000175:diagnosis* / Q000453:epidemiology; D002560:Cerebrovascular Circulation / Q000502:physiology; D003072:Cognition Disorders / Q000175:diagnosis / Q000453:epidemiology; D005260:Female; D005492:Folic Acid / Q000097:blood; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009186:Myelin Sheath / Q000378:metabolism; D009483:Neuropsychological Tests; D011159:Population Surveillance; D015995:Prevalence; D012307:Risk Factors; D012720:Severity of Illness Index; D014805:Vitamin B 12 / Q000097:blood*
D015415:Biomarkers; D006710:Homocysteine; D005492:Folic Acid; D014805:Vitamin B 12