Homocysteine and folate as risk factors for dementia and Alzheimer disease.
BACKGROUND
In cross-sectional studies, elevated plasma total homocysteine (tHcy) concentrations have been associated with cognitive impairment and dementia. Incidence studies of this issue are few and have produced conflicting results.


OBJECTIVE
We investigated the relation between high plasma tHcy concentrations and risk of dementia and Alzheimer disease (AD) in an elderly population.


METHODS
A dementia-free cohort of 816 subjects (434 women and 382 men; mean age: 74 y) from an Italian population-based study constituted our study sample. The relation of baseline plasma tHcy to the risk of newly diagnosed dementia and AD on follow-up was examined. A proportional hazards regression model was used to adjust for age, sex, education, apolipoprotein E genotype, vascular risk factors, and serum concentrations of folate and vitamin B-12.


RESULTS
Over an average follow-up of 4 y, dementia developed in 112 subjects, including 70 who received a diagnosis of AD. In the subjects with hyperhomocysteinemia (plasma tHcy > 15 micromol/L), the hazard ratio for dementia was 2.08 (95% CI: 1.31, 3.30; P = 0.002). The corresponding hazard ratio for AD was 2.11 (95% CI: 1.19, 3.76; P = 0.011). Independently of hyperhomocysteinemia and other confounders, low folate concentrations (< or = 11.8 nmol/L) were also associated with an increased risk of both dementia (1.87; 95% CI: 1.21, 2.89; P = 0.005) and AD (1.98; 95% CI: 1.15, 3.40; P = 0.014), whereas the association was not significant for vitamin B-12.


CONCLUSIONS
Elevated plasma tHcy concentrations and low serum folate concentrations are independent predictors of the development of dementia and AD.
Ravaglia
Giovanni
G
Department of Internal Medicine, Cardioangiology, and Hepatology, University Hospital S Orsola-Malpighi, Bologna, Italy. ravaglia@med.unibo.it
Forti
Paola
P
Maioli
Fabiola
F
Martelli
Mabel
M
Servadei
Lucia
L
Brunetti
Nicoletta
N
Porcellini
Elisa
E
Licastro
Federico
F
D000368:Aged; D000375:Aging / Q000097:blood* / Q000502:physiology / Q000523:psychology; D000544:Alzheimer Disease / Q000097:blood / Q000453:epidemiology*; D003071:Cognition / Q000502:physiology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003704:Dementia / Q000097:blood / Q000453:epidemiology*; D005260:Female; D005492:Folic Acid / Q000097:blood*; D005500:Follow-Up Studies; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors; D016036:Seroepidemiologic Studies
D006710:Homocysteine; D005492:Folic Acid