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Background. The associations of endogenous sex hormones with risk of dementia in the elderly population are not well known. Methods. The relationship of baseline serum total estradiol (E2) and free testosterone (FT) to 4-year risk of all-cause dementia, Alzheimer’s disease (AD), and vascular dementia (VaD) was examined in a dementia-free, population-based cohort of 433 women (mean age 74 years) and 376 men (mean age 73 years). Multivariable proportional hazards regression was used to adjust for sociodemographic and lifestyle variables, body mass index, apolipoprotein E genotype, cardiovascular conditions, and homocysteinemia. Results. Dementia developed in 71 women (46 AD, 21 VaD) and 39 men (23 AD, 12 VaD). In women with high E2 (serum E2 � 10 pg/mL), the multivariable-adjusted hazard ratio (HR) for dementia was 1.75 (95% confidence interval [CI], 1.06-2.89). The corresponding multivariable-adjusted HR for AD was 1.94 (95% CI, 1.04-3.61), whereas no association was found for VaD. No association with dementia was found for serum FT in women and for either serum E2 or FT in men. Conclusion. High serum E2 is an independent predictor for dementia and AD in elderly women.

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 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.

Background. Bone loss in elderly men is associated with changes in body composition and reduced secretion of endogenous anabolizing hormones. The independent influences of body composition and endocrine factors on male bone metabolism, however, are unclear. Methods. Bone mass density (BMD) (bone mass content [BMC, g]/projected bone area [BA, cm 2 ]) at different skeletal sites, skeletal muscle, and body fat mass were measured by dual-energy X-ray absorptiometry in 129 men aged 20 to 95 years. Free testosterone, 17- b -estradiol, dehydroepiandrosterone-sulfate, and insulin-like growth factor 1 (IGF-1) serum concentrations were measured. Because BMD may fail to control for differences in skeletal size, the associations of bone mass with body composition and hormones were studied by comparing BMD regression models incorporating age and knee height only with BMC regression models also incorporating BA. Results. Skeletal muscle had close associations ( p at least , .01) with BMD and BMC at almost all skeletal sites, but the strength of these associations was generally reduced in BMC with respect to BMD models. Weak associations ( p , .05) were found in both models for fatness with femoral bone and for 17- b -estradiol with total body and femoral bone. The association of 17- b -estradiol with spinal bone was significant ( p , .05) in the BMD but not in the BMC model. No association of BMC or BMD with androgens and IGF-1 reached significancy. Conclusions. Skeletal muscle may be more important than fatness and anabolizing hormones in preserving bone mass in elderly men. In contrast to traditional belief, estrogens may be more important than androgens and IGF-1 in male bone metabolism.