Homocysteine, vitamin B-12, and folic acid and the risk of cognitive decline in old age: the Leiden 85-Plus study.
BACKGROUND
High concentrations of homocysteine and low concentrations of vitamin B-12 and folic acid are frequently observed in subjects with dementia.


OBJECTIVE
We assessed whether serum concentrations of homocysteine, vitamin B-12, or folic acid predict cognitive decline in old age.


METHODS
This was a prospective, population-based, longitudinal study of 599 subjects (Leiden 85-Plus Study, Netherlands). The subjects were administered a battery of cognitive tests (including the Mini Mental State Examination, the Stroop test, a letter digit coding test, and a word recall test) at 85 y of age and yearly thereafter until 89 y of age. Serum concentrations of homocysteine, vitamin B-12, and folic acid were measured at 85 and 89 y of age. Cross-sectional associations between serum concentrations and cognition were assessed at 85 and 89 y of age. The association between baseline serum concentrations and subsequent longitudinal cognitive decline was assessed with the use of mixed linear models.


RESULTS
In the cross-sectional analyses, serum concentrations of homocysteine and folic acid were significantly associated with cognitive performance, but serum concentrations of vitamin B-12 were not. In the longitudinal analyses, there were no significant associations of serum concentrations of homocysteine, vitamin B-12, or folic acid with rate of cognitive decline.


CONCLUSIONS
Elevated serum concentrations of homocysteine and reduced folic acid are associated with cognitive impairment in elderly persons but do not predict an increased rate of cognitive decline. The association of high serum concentrations of homocysteine and low folic acid with cognitive impairment in old age is likely to be a consequence of disease and not a contributory cause.
Mooijaart
Simon P
SP
Departments of Gerontology and Geriatrics and Clinical Chemistry, Leiden University Medical Center, Leiden, Netherlands.
Gussekloo
Jacobijn
J
Frölich
Marijke
M
Jolles
Jelle
J
Stott
David J
DJ
Westendorp
Rudi G J
RG
de Craen
Anton J M
AJ
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood* / Q000502:physiology / Q000523:psychology*; D003071:Cognition / Q000502:physiology; D003430:Cross-Sectional Studies; D003704:Dementia / Q000097:blood* / Q000453:epidemiology; D005260:Female; D005492:Folic Acid / Q000097:blood*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D009483:Neuropsychological Tests; D011446:Prospective Studies; D012307:Risk Factors; D014805:Vitamin B 12 / Q000097:blood*
D006710:Homocysteine; D005492:Folic Acid; D014805:Vitamin B 12