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Background. Recent prospective studies reported that increased plasma homocysteine levels are an independent predictor of osteoporotic fracture in elderly persons. These studies, however, did not take into account folate and vitamin B12, which are the major nutritional determinants of homocysteinemia. Methods. Incident osteoporotic fractures were assessed in 702 Italian participants aged 65–94 years with a mean follow-up of 4 years (1999/2000–2003/2004). A multivariable logistic regression model was used to study the relation of baseline plasma homocysteine, serum folate, and serum vitamin B12 with risk of fracture. Results. After adjustment for sociodemographic and clinical confounders, the odds ratio (OR) for each increase of 1 standard deviation in log-transformed plasma homocysteine was 1.39 (95% confidence interval [CI], 1.01–1.91), but decreased to 1.22 (95% CI, 0.85–1.74) after further adjustment for serum folate and vitamin B12. The corresponding multivariable-adjusted OR for hyperhomocysteinemia (plasma total homocysteine [tHcy] . 15 lmoL) was 1.58 (95% CI, 0.71–3.53). Participants in the lowest serum folate quartile (� 9.3 nmol/L) had an increased risk of fracture than did those in higher quartiles (multivariable-adjusted OR ¼ 2.06; 95% CI. 1.02–4.18), but no dose-related protective effect for increasing serum folate levels was found (multivariable-adjusted OR ¼ 0.84 for each increase of 1 standard deviation in log-transformed serum folate, 95% CI, 0.59–1.19). No independent association was found for serum vitamin B12. Conclusions. Low serum folate is responsible for the association between homocysteine and risk of osteoporotic fracture in elderly persons.

Background: In cross-sectional studies, elevated plasma total homocysteine (tHcy) concentrations have been associated with cognitiveimpairmentanddementia.Incidencestudiesofthisissuearefew 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 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.

BACKGROUND Chronic low-grade inflammation, as measured with the peripheral serum marker C-reactive protein (sCRP), may be a risk factor for dementia in elderly persons. METHODS The relationship between sCRP and score on the Mini-Mental State Examination (MMSE), a commonly used screening cognitive measure, was investigated in 540 well functioning, healthy, and cognitively normal elders (age 73 +/- 6 years). Sociodemographic status, lifestyle, health status, traditional and nontraditional cardiovascular risk factors including plasma total homocysteine (tHcy), and other peripheral blood markers of vascular inflammation (leukocyte count, serum albumin, and plasma fibrinogen) were also assessed. RESULTS Risk for having sCRP in the highest decile (>0.7 mg/dl) was significantly higher in individuals with MMSE score 24-25 (odds ratio = 3.07, 95% confidence interval, 1.2-7.9) and 26-28 (odds ratio = 2.10, 95% confidence interval, 1.1-3.9) compared with those scoring above 28 (reference group). Results were unaffected by adjustment for all potential confounders. No association was found between MMSE and peripheral markers of vascular inflammation other than sCRP, but lower MMSE scores were also independently associated with hyperhomocysteinemia (plasma tHcy > 15 mmol/L). CONCLUSION In healthy, cognitively normal elderly community dwellers, increased sCRP levels are associated with concurrent cognitive impairment as measured by MMSE. The association is independent of sociodemographic status, lifestyle, health status, and traditional and nontraditional cardiovascular risk factors including hyperhomocysteinemia. Results support the hypothesis that chronic low-grade inflammation may be involved in age-related cognitive impairment.