Homocysteine and folate as risk factors for dementia and Alzheimer disease

被引:385
作者
Ravaglia, G
Forti, P
Maioli, F
Martelli, M
Servadei, L
Brunetti, N
Porcellini, E
Licastro, F
机构
[1] Univ Hosp S Orsola Malphigi, Dept Internal Med Cardioangiol & Hepatol, I-40138 Bologna, Italy
[2] Univ Bologna, Dept Expt Pathol, I-40126 Bologna, Italy
关键词
homocysteine; dementia; Alzheimer disease; incidence; folate;
D O I
10.1093/ajcn/82.3.636
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 ;
摘要
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. Design: 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 mu mol/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 (<= 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.
引用
收藏
页码:636 / 643
页数:8
相关论文
共 42 条
[1]   Homocysteine, vitamin B6, and vascular disease in patients with AD [J].
Borroni, B ;
Agosti, C ;
Panzali, AF ;
Di Luca, M ;
Padovani, A .
NEUROLOGY, 2002, 59 (09) :1475-1475
[2]   Plasma total homocysteine and cognitive performance in a volunteer elderly population [J].
Budge, M ;
Johnston, C ;
Hogervorst, E ;
De Jager, C ;
Milwain, E ;
Iversen, SD ;
Barnetson, L ;
King, E ;
Smith, AD .
VASCULAR FACTORS IN ALZHEIMER'S DISEASE, 2000, 903 :407-410
[3]   B vitamins, cognition, and aging: A review [J].
Calvaresi, E ;
Bryan, J .
JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES, 2001, 56 (06) :P327-P339
[4]   The mental deterioration battery: Normative data, diagnostic reliability and qualitative analyses of cognitive impairment [J].
Carlesimo, GA ;
Caltagirone, C ;
Gainotti, G ;
Fadda, L ;
Gallassi, R ;
Lorusso, S ;
Marfia, G ;
Marra, C ;
Nocentini, U ;
Parnetti, L .
EUROPEAN NEUROLOGY, 1996, 36 (06) :378-384
[5]   Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease [J].
Clarke, R ;
Smith, AD ;
Jobst, KA ;
Refsum, H ;
Sutton, L ;
Ueland, PM .
ARCHIVES OF NEUROLOGY, 1998, 55 (11) :1449-1455
[6]   Homocysteine and risk of ischemic heart disease and stroke -: A meta-analysis [J].
Clarke, R ;
Collins, R ;
Lewington, S ;
Donald, A ;
Alfthan, G ;
Tuomilehto, J ;
Arnesen, E ;
Bonaa, K ;
Blacher, J ;
Boers, GHJ ;
Bostom, A ;
Bots, ML ;
Grobee, DE ;
Brattström, L ;
Breteler, MMB ;
Hofman, A ;
Chambers, JC ;
Kooner, JS ;
Coull, BM ;
Evans, RW ;
Kuller, LH ;
Evers, S ;
Folsom, AR ;
Freyburger, G ;
Parrot, F ;
Genst, J ;
Dalery, K ;
Graham, IM ;
Daly, L ;
Hoogeveen, EK ;
Kostense, PJ ;
Stehouwer, CDA ;
Hopknis, PN ;
Jacques, P ;
Selhub, J ;
Luft, FC ;
Jungers, P ;
Lindgren, A ;
Lolin, YI ;
Loehrer, F ;
Fowler, B ;
Mansoor, MA ;
Malinow, MR ;
Ducimetiere, P ;
Nygard, O ;
Refsum, H ;
Vollset, SE ;
Ueland, PM ;
Omenn, GS ;
Beresford, SAA .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2002, 288 (16) :2015-2022
[7]  
Fassbender K, 1999, LANCET, V353, P1586
[8]   Homocysteine: a sulph'rous fire [J].
Hajjar, KA .
JOURNAL OF CLINICAL INVESTIGATION, 2001, 107 (06) :663-664
[9]   Hyperhomocysteinemia in high-aged subjects: relation of B-vitamins, folic acid, renal function and the methylenetetrahydrofolate reductase mutation [J].
Herrmann, W ;
Quast, S ;
Ullrich, M ;
Schultze, H ;
Bodis, M ;
Geisel, J .
ATHEROSCLEROSIS, 1999, 144 (01) :91-101
[10]   Similarities between Alzheimer's disease and vascular dementia [J].
Kalaria, R .
JOURNAL OF THE NEUROLOGICAL SCIENCES, 2002, 203 :29-34