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BACKGROUND: The role of total calcium intake in the prevention of hip fracture risk has not been well established. OBJECTIVE: The objective of the study was to assess the relation of calcium intake to the risk of hip fracture on the basis of meta-analyses of cohort studies and clinical trials. RESULTS: In women (7 prospective cohort studies, 170,991 women, 2,954 hip fractures), there was no association between total calcium intake and hip fracture risk [pooled risk ratio (RR) per 300 mg total Ca/d = 1.01; 95% CI: 0.97, 1.05]. In men (5 prospective cohort studies, 68,606 men, 214 hip fractures), the pooled RR per 300 mg total Ca/d was 0.92 (95% CI: 0.82, 1.03). On the basis of 5 clinical trials (n = 5666 women, primarily postmenopausal, plus 1074 men) with 814 nonvertebral fractures, the pooled RR for nonvertebral fractures between calcium supplementation (800-1600 mg/d) and placebo was 0.92 (95% CI: 0.81, 1.05). On the basis of 4 clinical trials with separate results for hip fracture (6,504 subjects with 139 hip fractures), the pooled RR between calcium and placebo was 1.64 (95% CI:1.02, 2.64). Sensitivity analyses including 2 additional small trials with <100 participants or per-protocol results did not substantially alter results. CONCLUSIONS: Pooled results from prospective cohort studies suggest that calcium intake is not significantly associated with hip fracture risk in women or men. Pooled results from randomized controlled trials show no reduction in hip fracture risk with calcium supplementation, and an increased risk is possible. For any nonvertebral fractures, there was a neutral effect in the randomized trials. [ABSTRACT FROM AUTHOR]

The current high life expectancy is overshadowed by neurodegenerative illnesses that lead to dementia and dependence. Alzheimer's disease (AD) is the most common of these conditions, and is considered to be a proteinopathy, with amyloid-beta42 as a key factor, leading via a cascade of events to neurodegeneration. Major factors involved are oxidative stress, perturbed Ca homeostasis and impaired energy metabolism. Protection against oxidative stress by micronutrients (including secondary bioactive substances) has been shown in transgenic Alzheimer model systems to delay AD. Epidemiological evidence is less conclusive, but the vast majority of the evidence supports a protective effect on cognitive functions in old age and AD. Thus, a diet rich in fruits and vegetables but also containing meat and fish is the most suitable to provide adequate micronutrients. The strong link between cardiovascular risk and AD may be explained by common pathogenetic mechanisms mediated, for example, by homocysteine and thus dependant on B-vitamins (folate and vitamins B(12) and B(6)). However, micronutrients may also be harmful. The high affinity of amyloid for metals (Fe, Al and Zn) favours the generation of reactive oxygen species and triggers an inflammatory response. Micronutrients in a balanced diet have a long-lasting, albeit low, protective impact on brain aging, hence prevention should be life long. [ABSTRACT FROM AUTHOR]

The influence of bopindolol monotherapy on blood pressure and plasma lipid fractions was investigated in 24 hypertensive patients. Bopindolol lowered blood pressure and heart rate significantly. When compared with placebo no changes were found in the plasma concentrations of total cholesterol, LDL cholesterol and HDL cholesterol. Plasma triglycerides were significantly increased after 4 and 8 weeks but not after 12 weeks of bopindolol. It is concluded that bopindolol is an effective and well tolerated beta-adrenoceptor blocker in hypertensive patients. The fact that it does not lower HDL cholesterol could be a potential advantage. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to test the individual and combined benefit of vitamin D, omega-3, and a simple home strength exercise program on the risk of any invasive cancer. Design: The DO-HEALTH trial is a three-year, multicenter, 2 × 2 × 2 factorial design double-blind, randomized-controlled trial to test the individual and combined benefit of three public health interventions. Setting: The trial was conducted between December 2012 and December 2017 in five European countries. Participants: Generally healthy community-dwelling adults ≥70 years were recruited. Interventions: Supplemental 2000 IU/day of vitamin D 3 , and/or 1 g/day of marine omega-3s, and/or a simple home strength exercise (SHEP) programme compared to placebo and control exercise. Main outcome: In this pre-defined exploratory analysis, time-to-development of any verified invasive cancer was the primary outcome in an adjusted, intent-to-treat analysis. Results: In total, 2,157 participants (mean age 74.9 years; 61.7% women; 40.7% with 25-OH vitamin D below 20 /ml, 83% at least moderately physically active) were randomized. Over a median follow-up of 2.99 years, 81 invasive cancer cases were diagnosed and verified. For the three individual treatments, the adjusted hazard ratios (HRs, 95% CI, cases intervention versus control) were 0.76 (0.49-1.18; 36 vs. 45) for vitamin D 3 , 0.70 (0.44-1.09, 32 vs. 49) for omega-3s, and 0.74 (0.48-1.15, 35 vs. 46) for SHEP. For combinations of two treatments, adjusted HRs were 0.53 (0.28-1.00; 15 vs. 28 cases) for omega-3s plus vitamin D 3 ; 0.56 (0.30-1.04; 11 vs. 21) for vitamin D 3 plus SHEP; and 0.52 (0.28-0.97; 12 vs. 26 cases) for omega-3s plus SHEP. For all three treatments combined, the adjusted HR was 0.39 (0.18-0.85; 4 vs. 12 cases). Conclusion: Supplementation with daily high-dose vitamin D 3 plus omega-3s, combined with SHEP, showed cumulative reduction in the cancer risk in generally healthy and active and largely vitamin D-replete adults ≥70 years. Clinical Trial Registration: ClinicalTrials.gov, Identifier: NCT01745263., Competing Interests: As part of the DO-HEALTH independent and investigator-initiated clinical trial, HB-F reports as the PI of the DO-HEALTH trial, grants from the European Commission (Grant Agreement No. 176;278588), from the University of Zurich, from NESTEC, from PFIZER Consumer Healthcare, from Streuli Pharma, plus non-financial support from DSM Nutritional Products and from Roche Diagnostics. Furthermore, HB-F reports speaker fees from Wild, Pfizer, Vifor, Mylan, Roche Diagnostics, and independent and investigator-initiated grants from Pfizer and from Vifor, outside the submitted work. JM reports grants from the National Institutes of Health, grants and non-financial support from Mars Symbioscience, outside the submitted work. BV reports personal fees from BIOGEN, CERECIN, ROCHE, and MSD, outside the submitted work. RR reports personal fees from Abiogen, Danone, Echolight, EMF, Mithra, ObsEva, Pfizer Consumer Health, and Theramex, outside the submitted work. JS is the scientific director of Forum D: a website dedicated to the critical revision and dissemination of knowledge regarding the medical uses of Vitamin D. EO reports a grant from Zurich University, during the conduct of the study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bischoff-Ferrari, Willett, Manson, Dawson-Hughes, Manz, Theiler, Braendle, Vellas, Rizzoli, Kressig, Staehelin, Da Silva, Armbrecht, Egli, Kanis, Orav and Gaengler.)

Importance: The benefits of vitamin D, omega-3 fatty acids, and exercise in disease prevention remain unclear., Objective: To test whether vitamin D, omega-3s, and a strength-training exercise program, alone or in combination, improved 6 health outcomes among older adults., Design, Setting, and Participants: Double-blind, placebo-controlled, 2 × 2 × 2 factorial randomized clinical trial among 2157 adults aged 70 years or older who had no major health events in the 5 years prior to enrollment and had sufficient mobility and good cognitive status. Patients were recruited between December 2012 and November 2014, and final follow-up was in November 2017., Interventions: Participants were randomized to 3 years of intervention in 1 of the following 8 groups: 2000 IU/d of vitamin D3, 1 g/d of omega-3s, and a strength-training exercise program (n = 264); vitamin D3 and omega-3s (n = 265); vitamin D3 and exercise (n = 275); vitamin D3 alone (n = 272); omega-3s and exercise (n = 275); omega-3s alone (n = 269); exercise alone (n = 267); or placebo (n = 270)., Main Outcomes and Measures: The 6 primary outcomes were change in systolic and diastolic blood pressure (BP), Short Physical Performance Battery (SPPB), Montreal Cognitive Assessment (MoCA), and incidence rates (IRs) of nonvertebral fractures and infections over 3 years. Based on multiple comparisons of 6 primary end points, 99% confidence intervals are presented and P < .01 was required for statistical significance., Results: Among 2157 randomized participants (mean age, 74.9 years; 61.7% women), 1900 (88%) completed the study. Median follow-up was 2.99 years. Overall, there were no statistically significant benefits of any intervention individually or in combination for the 6 end points at 3 years. For instance, the differences in mean change in systolic BP with vitamin D vs no vitamin D and with omega-3s vs no omega-3s were both -0.8 (99% CI, -2.1 to 0.5) mm Hg, with P < .13 and P < .11, respectively; the difference in mean change in diastolic BP with omega-3s vs no omega-3s was -0.5 (99% CI, -1.2 to 0.2) mm Hg; P = .06); and the difference in mean change in IR of infections with omega-3s vs no omega-3s was -0.13 (99% CI, -0.23 to -0.03), with an IR ratio of 0.89 (99% CI, 0.78-1.01; P = .02). No effects were found on the outcomes of SPPB, MoCA, and incidence of nonvertebral fractures). A total of 25 deaths were reported, with similar numbers in all treatment groups., Conclusions and Relevance: Among adults without major comorbidities aged 70 years or older, treatment with vitamin D3, omega-3s, or a strength-training exercise program did not result in statistically significant differences in improvement in systolic or diastolic blood pressure, nonvertebral fractures, physical performance, infection rates, or cognitive function. These findings do not support the effectiveness of these 3 interventions for these clinical outcomes., Trial Registration: ClinicalTrials.gov Identifier: NCT01745263.

Objectives: To evaluate 2 simple strategies, vitamin D 3 and a home exercise program, in functional recovery during the first year after hip fracture., Design: Secondary analysis of a factorial clinical trial. Patients were randomly allocated to 800 IU (standard of care) or 2000 IU vitamin D 3 and a daily instruction of a simple home exercise program (SHEP) or standard physiotherapy alone during acute care., Setting and Participants: Acute hip fracture patients aged ≥65 years, after hip fracture surgery, admitted to a large hospital in Zurich, Switzerland., Measures: Three objective measures of lower extremity function were assessed at baseline and 6 and 12 months, with the Timed Up and Go test (TUG) as the primary endpoint, and knee flexor and extensor strength, and a self-reported physical function score (PF-10) as secondary endpoints. Linear mixed model regression analyses were based on intention to treat, adjusting for baseline function, time, age, sex, and baseline 25-hydroxyvitamin D level., Results: We enrolled 173 patients (79.2% women; mean age 84 years; 77.5% living at home). A significant interaction was found between vitamin D 3 dose and SHEP for TUG (P = .045). Thus, findings compared the standard of care reference arm with 800 IU vitamin D 3 without SHEP to 3 interventions arms (800 IU vitamin D 3 +SHEP; 2000 IU vitamin D 3 without SHEP; 2000 IU vitamin D 3 +SHEP). For TUG, over 12 months the 800 IU vitamin D 3 +SHEP group performed significantly better than the standard-of-care group (13.8 vs 19.5 seconds; P = .01). Findings for knee flexor strength were in line with TUG results and approached significance (P = .07), whereas knee extensor strength and PF-10 did not differ by treatments., Conclusions/implications: For functional recovery after hip fracture, combining home exercise with 800 IU vitamin D 3 is superior to no home exercise or 2000 IU vitamin D 3 . None of the interventions improved subjective physical functioning., (Copyright © 2018 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To test whether daily high-dose vitamin D improves recovery after unilateral total knee replacement., Methods: Data come from a 24-month randomised, double-blind clinical trial. Adults aged 60 and older undergoing unilateral joint replacement due to severe knee osteoarthritis were 6-8 weeks after surgery randomly assigned to receive daily high-dose (2000 IU) or standard-dose (800 IU) vitamin D 3 . The primary endpoints were symptoms (Western Ontario and McMaster Universities Arthritis Index pain and function scores) assessed at baseline, 6, 12, 18 and 24 months in both knees, and the rate of falls over 24 months. The secondary outcomes were sit-to-stand performance, gait speed, physical activity and radiographic progression in the contralateral knee., Results: We recruited 273 participants, 137 were randomised to receive 2000 IU and 136 were randomised to receive 800 IU vitamin D per day. 2000 IU vitamin D increased 25-hydroxyvitamin D levels to 45.6 ng/mL and 800 IU vitamin D to 37.1 ng/mL at month 24 (p<0.0001). While symptoms improved significantly in the operated knee and remained stable in the contralateral knee over time, none of the primary or secondary endpoints differed by treatment group over time. The rate of falls over 24 months was 1.05 with 2000 IU and 1.07 with 800 IU (p=0.84). 30.5% of participants in the 2000 IU and 31.3% of participants in the 800 IU group had radiographic progression in the contralateral knee over 24 months (p=0.88)., Conclusions: Our findings suggest that a 24-month treatment with daily 2000 IU vitamin D did not show greater benefits or harm than a daily standard dose of 800 IU among older adults undergoing unilateral total knee replacement., Competing Interests: Competing interests: None declared.

Objectives: To determine whether statin use alters response of 25-hydroxyvitamin D (25(OH)D) level to vitamin D treatment., Design: Pooled analysis., Setting: Three double-blind randomized controlled trials that tested different doses of vitamin D., Participants: Participants of three trials (N = 646; mean age 76.3 ± 8.4, 65% female)., Measurements: In all three trials, 25(OH)D status and statin use were assessed repeatedly over time (baseline, 6 and 12 months). Repeated-measures analysis was used to compare 25(OH)D response to vitamin D treatment at baseline and 6 and 12 months of statin users and nonusers, controlling for age, sex, body mass index, Charlson Comorbidity Index, vitamin D dose, trial, and season., Results: At baseline, 17.5% were statin users, and 65% were vitamin D deficient (25(OH)D < 20 ng/mL). Baseline 25(OH)D levels did not differ significantly between groups at baseline (18.8 for statin users, 17.2 ng/mL for nonusers, P = .07), but according to the longitudinal analyses, the total increase over 12 months in 25(OH)D concentration was significantly lower in statin users (13.1 ng/L) than nonusers (15.9 ng/mL; 21.4% difference; P = .009)., Conclusion: Of persons aged 60 and older at high risk of vitamin D deficiency, statin users had a 21.4% smaller increase in 25(OH)D serum concentrations over time than nonusers, independent of vitamin D dose and other covariates., (© 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.)

Importance: Vitamin D deficiency has been associated with poor physical performance., Objective: To determine the effectiveness of high-dose vitamin D in lowering the risk of functional decline., Design, Setting, and Participants: One-year, double-blind, randomized clinical trial conducted in Zurich, Switzerland. The screening phase was December 1, 2009, to May 31, 2010, and the last study visit was in May 2011. The dates of our analysis were June 15, 2012, to October 10, 2015. Participants were 200 community-dwelling men and women 70 years and older with a prior fall., Interventions: Three study groups with monthly treatments, including a low-dose control group receiving 24,000 IU of vitamin D3 (24,000 IU group), a group receiving 60,000 IU of vitamin D3 (60,000 IU group), and a group receiving 24,000 IU of vitamin D3 plus 300 μg of calcifediol (24,000 IU plus calcifediol group)., Main Outcomes and Measures: The primary end point was improving lower extremity function (on the Short Physical Performance Battery) and achieving 25-hydroxyvitamin D levels of at least 30 ng/mL at 6 and 12 months. A secondary end point was monthly reported falls. Analyses were adjusted for age, sex, and body mass index., Results: The study cohort comprised 200 participants (men and women ≥ 70 years with a prior fall). Their mean age was 78 years, 67.0% (134 of 200) were female, and 58.0% (116 of 200) were vitamin D deficient (<20 ng/mL) at baseline. Intent-to-treat analyses showed that, while 60,000 IU and 24,000 IU plus calcifediol were more likely than 24,000 IU to result in 25-hydroxyvitamin D levels of at least 30 ng/mL (P = .001), they were not more effective in improving lower extremity function, which did not differ among the treatment groups (P = .26). However, over the 12-month follow-up, the incidence of falls differed significantly among the treatment groups, with higher incidences in the 60,000 IU group (66.9%; 95% CI, 54.4% to 77.5%) and the 24,000 IU plus calcifediol group (66.1%; 95% CI, 53.5%-76.8%) group compared with the 24,000 IU group (47.9%; 95% CI, 35.8%-60.3%) (P = .048). Consistent with the incidence of falls, the mean number of falls differed marginally by treatment group. The 60,000 IU group (mean, 1.47) and the 24,000 IU plus calcifediol group (mean, 1.24) had higher mean numbers of falls compared with the 24,000 IU group (mean, 0.94) (P = .09)., Conclusions and Relevance: Although higher monthly doses of vitamin D were effective in reaching a threshold of at least 30 ng/mL of 25-hydroxyvitamin D, they had no benefit on lower extremity function and were associated with increased risk of falls compared with 24,000 IU., Trial Registration: clinicaltrials.gov Identifier: NCT01017354.

Unlabelled: In this study, we compare the extent to which seven available definitions of sarcopenia and two related definitions predict the rate of falling. Our results suggest that the definitions of Baumgartner and Cruz-Jentoft best predict the rate of falls among sarcopenic versus non-sarcopenic community-dwelling seniors., Introduction: The purpose of the study is to compare the extent to which seven available definitions of sarcopenia and two related definitions predict the prospective rate of falling., Methods: We studied a cohort of 445 seniors (mean age 71 years, 45 % men) living in the community who were followed with a detailed fall assessment for 3 years. For comparing the rate of falls in sarcopenic versus non-sarcopenic individuals, we used multivariate Poisson regression analyses adjusting for gender and treatment (original intervention tested vitamin D plus calcium against placebo). Of the seven available definitions, three were based on low lean mass alone (Baumgartner, Delmonico 1 and 2) and four required both low muscle mass and decreased performance in a functional test (Fielding, Cruz-Jentoft, Morley, Muscaritoli). The two related definitions were based on low lean mass alone (Studenski 1) and low lean mass contributing to weakness (Studenski 2)., Results: Among 445 participants, 231 fell, sustaining 514 falls over the 3-year follow-up. The prospective rate of falls in sarcopenic versus non-sarcopenic individuals was best predicted by the Baumgartner definition based on low lean mass alone (RR = 1.54; 95 % CI 1.09-2.18) with 11 % prevalence of sarcopenia and the Cruz-Jentoft definition based on low lean mass plus decreased functional performance (RR = 1.82; 95 % CI 1.24-2.69) with 7.1 % prevalence of sarcopenia. Consistently, fall rate was non-significantly higher in sarcopenic versus non-sarcopenic individuals based on the definitions of Delmonico 1, Fielding, and Morley., Conclusion: Among the definitions investigated, the Baumgartner definition and the Cruz-Jentoft definition had the highest validity for predicting the rate of falls.

Unlabelled: In this double-blind RCT, 4-month treatment with calcifediol compared with vitamin D3 improved gait speed by 18% among young postmenopausal women. Consistently, change in 25(OH)D blood levels over time were significantly correlated with improvement in gait speed in these women. No effect could be demonstrated for trunk sway., Introduction: The aim of this study is to test the effect of calcifediol compared with vitamin D3 on gait speed and trunk sway., Methods: Twenty healthy postmenopausal women with an average 25(OH)D level of 13.2 ng/ml (SD = ±3.9) and a mean age of 61.5 years (SD = ±7.2) were randomized to either 20 μg of calcifediol or 20 μg (800 IU) of vitamin D3 per day in a double-blind manner. At baseline and at 4 months of follow-up, the same physiotherapist blinded to treatment allocation tested 8-m gait speed and a body sway test battery (Sway star pitch and roll angle plus velocity while walking 8 m, and standing on both legs on a hard and soft surface). All analyses adjusted for baseline measurement, age, and body mass index., Results: Mean 25(OH)D levels increased to 69.3 ng/ml (SD = ±9.5) in the calcifediol group and to 30.5 ng/ml (SD = ±5.0) in the vitamin D3 group (p < 0.0001). Women receiving calcifediol compared with vitamin D3 had an 18% greater improvement in gait speed at 4-month follow-up (p = 0.046) adjusting for baseline gait speed, age, and body mass index. Also, change in gait speed was significantly correlated with change in serum 25(OH)D concentrations (r = 0.5; p = 0.04). Across three tests of trunk sway, there were no consistent differences between groups and no significant correlation between change in 25(OH)D serum concentrations and change in trunk sway., Conclusions: Calcifediol improved gait speed in early postmenopausal women compared with vitamin D3 and change in 25(OH)D level was moderately correlated with improvement in gait speed. A benefit on trunk sway could not be demonstrated.

Aim: Long-term pharmacokinetics after supplementation with vitamin D3 or calcifediol (the 25-hydroxyvitamin D3 metabolite) is not well studied. Additionally, it is unclear whether bolus doses of vitamin D3 or calcifediol lead to 25(OH)D3 plasma concentrations considered desirable for fracture prevention (30 ng/mL). We therefore investigated plasma pharmacokinetics of 25(OH)D3 during different vitamin D3 and calcifediol supplementation regimens., Methods: In this seven-arm, randomized, double-blind, controlled parallel-group study, 35 healthy females aged 50–70 years (5 per group) received 20 μg calcifediol or vitamin D(3) daily, 140 μg calcifediol or vitamin D(3) weekly, for 15 weeks, or a single bolus of either 140 μg calcifediol, or vitamin D(3), or both. 25(OH)D3 plasma concentrations were quantified using LC–MS/MS in 14 clinical visits among all participants., Results: For daily (weekly) dosing, the area under the concentration–time curve (AUC0–24h), which is the measure for exposure, was 28% (67%) higher after the first dose of calcifediol than after the first dose of vitamin D3. After 15 weeks, this difference was 123% (178%). All women in the daily and weekly calcifediol groups achieved 25(OH)D3 concentrations > 30 ng/mL (mean, 16.8 days), but only 70% in the vitamin D3 daily or weekly groups reached this concentration (mean, 68.4 days). A single dose of 140 μg calcifediol led to 117% higher 25(OH)D3 AUC0–96h values than 140 μg vitamin D3, while the simultaneous intake of both did not further increase exposure., Conclusions: Calcifediol given daily, weekly, or as a single bolus is about 2–3 times more potent in increasing plasma 25(OH)D3 concentrations than vitamin D3. Plasma 25(OH)D3 concentrations of 30 ng/mL were reached more rapidly and reliably with calcifediol.

Unlabelled: Our findings show that only about 20% of seniors receive vitamin D supplementation prior to their index hip fracture or after the event. We further confirm the high prevalence of severe vitamin D deficiency in this population and show that those who receive supplementation have significantly higher 25-hydroxyvitamin D (25(OH)D) status., Introduction: The aim of this study is to assess current practice in pre- and post-hip fracture care practice with respect to vitamin D supplementation., Methods: We surveyed 1,090 acute hip fracture patients age 65 and older admitted to acute care for hip fracture repair; 844 had serum 25-hydroxyvitamin D levels measured upon admission to acute care, and 362 agreed to be followed at 12 month after their hip fracture. Prevalence of vitamin D supplementation was assessed upon admission to acute care (at the time of hip fracture), upon discharge from acute care, and at 6 and 12 months follow-up., Results: Of 1,090 acute hip fracture patients (mean age 85 years, 78% women, 59 % community-dwelling), 19% had received any dose of vitamin D prior to the index hip fracture, 27% (of 854 assessed) at discharge from acute care, 22 % (of 321 assessed) at 6 month, and 21% (of 285 assessed) at 12 month after their hip fracture. At the time of fracture, 45% had 25(OH)D levels below 10 ng/ml, 81% had levels below 20 ng/ml, and 96% had levels below 30 ng/ml. Notably, 25(OH)D levels did not differ by season or gender but were significantly higher among 164 hip fracture patients, with any vitamin D supplementation compared with 680 without supplementation (19.9 versus 10.8 ng/ml; p < 0.0001)., Conclusion: Only about 20% of seniors receive vitamin D at the time of their fracture and after the event. This is despite the documented 81% prevalence of vitamin D deficiency. Interdisciplinary efforts may be warranted to improve vitamin D supplementation in seniors both before a hip fracture occurs and after.

Background: It is not well established if and to what extent mild to moderate cognitive impairment predicts mortality and risk of nursing home admission after hip fracture., Objective: To investigate prospectively whether and to what extent mild to moderate cognitive impairment, contributes to mortality and admission to nursing home in the first year after acute hip fracture., Methods: We enrolled 173 patients with acute hip fracture age 65 and older who reached a Mini-Mental State Examination (MMSE) score of at least 15 during acute care after hip fracture repair. An MMSE score of 15 to 24 (median) was classified as mild to moderate cognitive impairment. Primary outcomes were mortality in all and admission to nursing home among seniors who lived at home prior to their hip fracture. Follow-up was 12 months with clinical visits at baseline, 6, and 12 months, plus monthly phone calls. We used Cox proportional hazards models controlling for age, sex, body mass index, baseline number of comorbidities and 25-hydroxyvitamin D status, and severe incident infections to assess the risk of mortality and nursing home admission. Because the study population was enrolled in a factorial design clinical trial testing high dose vitamin D and/or an exercise home program, all analyses also controlled for these treatment strategies., Results: Of 173 acute hip fracture patients enrolled, 79% were women, 77% were admitted from home, and 80% were vitamin D deficient (<20ng/ml). Mean age was 84 years. 54% had mild to moderate cognitive impairment. Over the 12-month follow-up, 20 patients died (27% of 173) and 47 (35% of 134) were newly admitted to a nursing home. Mild to moderate cognitive impairment was associated with a more than 5-fold increased risk of mortality (HR=5.77; 95% CI: 1.55-21.55) and a more than 7-fold increased risk of nursing home admission (HR=7.37; 95% CI: 1.75-30.95). Additional independent risk factors of mortality were male gender (HR=3.55; 95% CI: 1.26-9.97), low BMI (HR=7.25; 95% CI: 1.61-33.74), and baseline 25-hydroxyvitamin D level (per 1ng/ml: HR=0.93; 95% CI: 0.87-0.998; p=0.04)., Conclusions: Mild to moderate cognitive impairment in patients with acute hip fracture is associated with a high risk of mortality and nursing home admission during the first year after hip fracture. Female gender, a greater BMI and a higher 25-hydroxyvitamin D status may protect against mortality after hip fracture independent of cognitive function., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Milk contains calcium, phosphorus, and protein and is fortified with vitamin D in the United States. All these ingredients may improve bone health. However, the potential benefit of milk on hip fracture prevention is not well established. The objective of this study was to assess the association of milk intake with risk of hip fracture based on a meta-analysis of cohort studies in middle-aged or older men and women. Data sources for this study were English and non-English publications via Medline (Ovid, PubMed) and EMBASE search up to June 2010, experts in the field, and reference lists. The idea was to compare prospective cohort studies on the same scale so that we could calculate the relative risk (RR) of hip fracture per glass of milk intake daily (approximately 300 mg calcium per glass of milk). Pooled analyses were based on random effects models. The data were extracted by two independent observers. The results show that in women (6 studies, 195,102 women, 3574 hip fractures), there was no overall association between total milk intake and hip fracture risk (pooled RR per glass of milk per day = 0.99; 95% confidence interval [CI] 0.96-1.02; Q-test p = .37). In men (3 studies, 75,149 men, 195 hip fractures), the pooled RR per daily glass of milk was 0.91 (95% CI 0.81-1.01). Our conclusion is that in our meta-analysis of cohort studies, there was no overall association between milk intake and hip fracture risk in women but that more data are needed in men., (Copyright © 2011 American Society for Bone and Mineral Research.)

Objective: To test the efficacy of supplemental vitamin D and active forms of vitamin D with or without calcium in preventing falls among older individuals., Data Sources: We searched Medline, the Cochrane central register of controlled trials, BIOSIS, and Embase up to August 2008 for relevant articles. Further studies were identified by consulting clinical experts, bibliographies, and abstracts. We contacted authors for additional data when necessary. Review methods Only double blind randomised controlled trials of older individuals (mean age 65 years or older) receiving a defined oral dose of supplemental vitamin D (vitamin D(3) (cholecalciferol) or vitamin D(2) (ergocalciferol)) or an active form of vitamin D (1alpha-hydroxyvitamin D(3) (1alpha-hydroxycalciferol) or 1,25-dihydroxyvitamin D(3) (1,25-dihydroxycholecalciferol)) and with sufficiently specified fall assessment were considered for inclusion., Results: Eight randomised controlled trials (n=2426) of supplemental vitamin D met our inclusion criteria. Heterogeneity among trials was observed for dose of vitamin D (700-1000 IU/day v 200-600 IU/day; P=0.02) and achieved 25-hydroxyvitamin D(3) concentration (25(OH)D concentration: <60 nmol/l v >or=60 nmol/l; P=0.005). High dose supplemental vitamin D reduced fall risk by 19% (pooled relative risk (RR) 0.81, 95% CI 0.71 to 0.92; n=1921 from seven trials), whereas achieved serum 25(OH)D concentrations of 60 nmol/l or more resulted in a 23% fall reduction (pooled RR 0.77, 95% CI 0.65 to 0.90). Falls were not notably reduced by low dose supplemental vitamin D (pooled RR 1.10, 95% CI 0.89 to 1.35; n=505 from two trials) or by achieved serum 25-hydroxyvitamin D concentrations of less than 60 nmol/l (pooled RR 1.35, 95% CI 0.98 to 1.84). Two randomised controlled trials (n=624) of active forms of vitamin D met our inclusion criteria. Active forms of vitamin D reduced fall risk by 22% (pooled RR 0.78, 95% CI 0.64 to 0.94)., Conclusions: Supplemental vitamin D in a dose of 700-1000 IU a day reduced the risk of falling among older individuals by 19% and to a similar degree as active forms of vitamin D. Doses of supplemental vitamin D of less than 700 IU or serum 25-hydroxyvitamin D concentrations of less than 60 nmol/l may not reduce the risk of falling among older individuals.

Background: Since children have frequent contact with the health care system, while their young parents very often do not, screening children routinely might represent an important opportunity to target the young parents. We examined whether cardiovascular risk factors in children predicted the risk of their parents., Methods: Five silent (hypertension, high triglycerides, high LDL-, high non-HDL-, and low HDL-cholesterol) and two clinical apparent (general and central adiposity) risk factors were compared in 2720 child-parent pairs from a well-defined sample of German elementary school children and parents., Results: All clinical apparent and silent risk factors were significantly correlated between children and their parents, and most pronounced were those for three silent risk factors: HDL cholesterol, LDL cholesterol, and non-HDL cholesterol (correlation coefficient r=0.26-0.28). In multivariate models, adjusting for age and gender, child general and abdominal adiposity conferred a significant 2.9-fold and a 2.6-fold enhanced odds among parents of carrying the same risk factors. Similarly, abnormal LDL, HDL, or non-HDL among children conferred a significant 3.0-fold, 2.0-fold, or 2.9-fold increased odds among parents. The odds of parents appeared stronger if the child had the same sex only for clinical apparent risk factors, and most pronounced for general adiposity., Conclusions: Cardiovascular risk screening in children may serve as a case finding strategy for early prevention in high risk families. The inclusion of silent risk factors in a screening program of school children may be warranted for the high prevalence among children and enhanced case-finding potential among parents.

Nutrition is a central factor in today's observed aging of the population. However, the good prospect of longevity is overshadowed by the high prevalence of mental decline in old age. The most prevalent form of neurodegeneration is Alzheimer's disease(AD) reaching a prevalence of over 30 % above age 80.The question is reviewed whether nutrients may protect or slow down the age associated mental decline due to neuronal degeneration. The amyloid hypothesis states that the amyloid fragment (Abeta) originating from the metabolism of the amyloid precursor protein (APP) is neurotoxic and causes the damage to the neurons. The most popular hypothesis states that a deranged APP metabolism increases oxidative stress in addition to age associated increase. Thus, antioxidative nutrients could potentially protect against AD. Numerous observational studies demonstrate a positive correlation between a high intake of antioxidants and better cognitive function in the elderly; however these studies need to be interpreted with caution. Randomized controlled studies over sufficient long periods are not possible. A hypothesis gaining today more weight are the age-related proinflammattory cytokines. Observational studies show a reduced risk of AD in users of nonsteroidal anti-inflammatory drugs. Also omega-3 fatty acids are known to reduce cytokines could then lower the AD risk.

We review the potential of vitamin D for the prevention of falls and fractures. Evidence from randomized-controlled trials will be reviewed for both endpoints, as well as epidemiologic data that correlates higher 25-hydroxyvitamin D status with better bone and muscle health. This review summarizes the compelling dual benefit of vitamin D on bone and muscle health, a concept that is unique and important for optimal fracture prevention at higher age. We will review sources of vitamin D and calcium and also outline why calcium supplementation alone may not contribute to fracture prevention at higher age. This review concludes that vitamin D at a dose of at least 800 IU per day should be provided to all postmenopausal women and everybody starting at age 60 for optimal bone and muscle health. In combination with a vitamin D supplement, dairy products may be an optimal source of calcium at higher age as milk provides both calcium and protein.

Background: Most clinical guidelines for the prevention of hip fractures recommend 800 IU vitamin D per day. This dose shifted serum 25-hydroxyvitamin D levels (25(OH)D) in previous studies to between 60 and 100 nmol/l., Aim: To measure 25(OH)D levels and prevalence of vitamin D supplementation in individuals age 65+ with acute hip fracture., Methods: 222 consecutive hip fracture patients were investigated over a 12 month period. Mean age of patients was 86 years and 77% were women., Results: Mean serum 25(OH)D levels were low among hip fracture patients admitted from home (34.6 nmol/l), from assisted living (27.7 nmol/l), and from nursing homes (24 nmol/l). Severe vitamin D deficiency below 30 nmol/l was present in 60%, 80% were below 50 nmol/l, and less than 4% reached desirable levels of at least 75 nmol/l. Consistently, only 10% of hip fracture patients had any vitamin D supplementation on admission to acute care with significantly higher 25(OH)D levels among individuals supplemented with 800-880 IU/day (63.5 nmol/l). Controlling for age and gender, vitamin D supplementation, type of dwelling, and season were independently and significantly associated with 25(OH)D levels., Conclusion: These data provide evidence that current guidelines for the prevention of hip fractures need further effort to be translated into clinical practice.

The influence of calcitropic hormones on functional mobility has been studied in vitamin D (calcidiol) deficient elderly or elderly with a history of falls, however, data in community-dwelling independent vitamin D replete elderly are missing. We therefore assessed in an observational survey the association of calcidiol (25(OH)D3) and calcitriol (D-hormone / 1,25(OH)2D3) status as well as of daily calcium intake on functional mobility in older subjects We evaluated 192 women and 188 men, aged superior 70 years and living independently. Average Timed-up and go test (TUG-test) in seconds was taken as measure of functional mobility. Calcidiol and D-hormone serum concentrations and daily calcium intake were studied in multivariate controlled linear regression models with TUG-test performance as the dependent variable and/or as dichotomous variables (deficient vs. non-deficient, above vs. below the median, respectively). Subjects with low D-hormone serum concentrations took significantly more time to perform the TUG-test (low = 7.70s +/- 2.52 SD ; high = 6.70s +/- 1.29 SD; p = 0.004). In the linear multivariate controlled regression model increased D-hormone serum concentrations predicted better TUG-test performance (estimate -0.0007, p = 0.044). Participants with a calcium intake of > or =512 mg/day were significantly faster to perform the TUG-test than participants with a daily calcium intake of <512 mg/day (estimate:-0.43, p = 0.007). Other significant predictors of better TUG-test performance in both models were: male gender, less comorbid conditions, younger age, lower BMI, iPTH serum levels and creatinine clearance. Calcidiol serum levels were not associated with TUG-test performance. Higher D-hormone status and a calcium intake of > or =512 mg/day in community-dwelling independent older persons are significant determinants of better functional mobility. Therefore, to ensure optimal functional mobility, the care of older persons should address correction of D-hormone deficiency and increasing daily calcium intake.

A 30 cM broad genomic region on the long arm of chromosome 10 at 80 cM shows significant and consistent linkage with AD and with plasma concentration of the beta-amyloid peptide 1-42 (Abeta42). The PLAU gene, which is involved in the production and degradation of Abeta42, maps to that region and is therefore a strong positional candidate for association with sporadic AD. We analyzed the non-synonymous single nucleotide polymorphism (SNP) rs2227564 in two independent case-control series from Switzerland and Greece and investigated the influence of this SNP on cognition in elderly individuals. Because PLAU modulates the cleavage of the amyloid precursor protein (APP) and the degradation of Abeta, we also determined the levels of Abeta in the brain, plasma and in the cerebrospinal fluid (CSF). We found no evidence for association of this SNP with AD or with AD-related traits such as beta-amyloid load in the medial temporal lobe or Abeta42 concentration in the CSF and in plasma. Our findings do not support a major role of PLAU polymorphisms as susceptibility factors for AD and suggest that large-scale association studies which combine genetic information from populations with similar genetic background might prevent the generation of spurious associations. Although PLAU may be pathophysiologially related to AD, the contribution of common genetic variants of this gene to the risk for developing AD is likely to be low., (Copyright 2004 Wiley-Liss, Inc.)

Context: Falls among elderly individuals occur frequently, increase with age, and lead to substantial morbidity and mortality. The role of vitamin D in preventing falls among elderly people has not been well established., Objective: To assess the effectiveness of vitamin D in preventing an older person from falling., Data Sources: MEDLINE and the Cochrane Controlled Trials Register from January 1960 to February 2004, EMBASE from January 1991 to February 2004, clinical experts, bibliographies, and abstracts. Search terms included trial terms: randomized-controlled trial or controlled-clinical trial or random-allocation or double-blind method, or single-blind method or uncontrolled-trials with vitamin D terms: cholecalciferol or hydroxycholecalciferols or calcifediol or dihydroxycholecalciferols or calcitriol or vitamin D/aa[analogs & derivates] or ergocalciferol or vitamin D/bl[blood]; and with accidental falls or falls, and humans., Study Selection: We included only double-blind randomized, controlled trials (RCTs) of vitamin D in elderly populations (mean age, 60 years) that examined falls resulting from low trauma for which the method of fall ascertainment and definition of falls were defined explicitly. Studies including patients in unstable health states were excluded. Five of 38 identified studies were included in the primary analysis and 5 other studies were included in a sensitivity analysis., Data Extraction: Independent extraction by 3 authors using predefined data fields including study quality indicators., Data Synthesis: Based on 5 RCTs involving 1237 participants, vitamin D reduced the corrected odds ratio (OR) of falling by 22% (corrected OR, 0.78; 95% confidence interval [CI], 0.64-0.92) compared with patients receiving calcium or placebo. From the pooled risk difference, the number needed to treat (NNT) was 15 (95% CI, 8-53), or equivalently 15 patients would need to be treated with vitamin D to prevent 1 person from falling. The inclusion of 5 additional studies, involving 10 001 participants, in a sensitivity analysis resulted in a smaller but still significant effect size (corrected RR, 0.87; 95% CI, 0.80-0.96). Subgroup analyses suggested that the effect size was independent of calcium supplementation, type of vitamin D, duration of therapy, and sex, but reduced sample sizes made the results statistically nonsignificant for calcium supplementation, cholecalciferol, and among men., Conclusions: Vitamin D supplementation appears to reduce the risk of falls among ambulatory or institutionalized older individuals with stable health by more than 20%. Further studies examining the effect of alternative types of vitamin D and their doses, the role of calcium supplementation, and effects in men should be considered.

The European Academy for Medicine of Ageing, founded by professors in geriatric medicine, provides a geriatric education program for European postgraduate physicians in geriatric medicine who are future academics in geriatric medicine in their countries. The course is organized for 30 participants involved in four one week residential sessions over two years. The program of each session involves 20 teachers, and includes state of the art lectures, student's lectures and working-group discussions. A first course took place in 1995-96, a second in 1997-98, a third has been accomplished in 1999-00, a fourth for 2001-02 and a fifth is ongoing for 2003--2004. The sessions are subjected to an evaluation program regarding the skills of the students, the value of the presentations and the satisfaction about the educational activities. The evaluations of the four sessions of EAMA course II (1997-1998) are presented here, with emphasis on the changes across the sessions for the whole group and for the individual students. The results are good to excellent for the main goals of the course, both by self-evaluation and by peer-evaluation. The dynamic process of this European academic-oriented geriatric education program attracts an increasing number of participants seeking the necessary skills and expertise to obtain academic position in geriatrics, and to meet international colleagues for further collaborative opportunities. Changes and adaptations of the following programs are fostered by the evaluation program to enhance weaker points. Accordingly, improvements in the programs and in the evaluation methods have been introduced during the third course, and are tested during the fourth and the fifth course.

Sterol-regulatory element-binding protein (SREBP)-2 is a key regulator of cholesterol. When cells are deprived of cholesterol, proteolytic cleavage releases the NH(2)-terminal domain of SREBP-2 that binds and activates the promoters of SREBP-2-regulated genes including the genes encoding the low-density lipoprotein (LDL) receptor, 3-hydroxymethyl-3-glutaryl-(HMG-)CoA-synthase, and HMG-CoA-reductase. Thus, SREPB-2 gene activation leads to enhanced cholesterol uptake and biosynthesis. A novel protein polymorphism (SREBP-2-595A/G) discovered in the regulatory domain of human SREBP-2 was investigated regarding its impact on cholesterol homeostasis. In human embryonic kidney (HEK)-293-cells, the cleavage-rate of the SREBP-2-595A-isoform was slightly decreased compared to that of the SREBP-2-595G-isoform. Since cleavage of SREBP-2 activates the LDL receptor-mediated uptake of plasma cholesterol, we hypothesized the LDL receptor-mediated uptake to be decreased in homozygous SREBP-2-595A-carriers and thus, plasma total cholesterol (TC) to be higher than in SREBP-2-595G-carriers. Multiple linear regression analysis of population samples from Switzerland (N=1334) and Israel (N=923) demonstrated a significant positive, gene dose-dependent association of the SREBP-2-595A-isoform with higher plasma TC (P=0.001). This cholesterol-modulating effect was present in hypercholesterolaemic (DeltaTC=1.05 mmol/l, 14.4%; P=0.002; N=477), but absent in normocholesterolaemic subjects (DeltaTC=0.06 mmol/l, 1.4%; P=0.334; N=1780). In summary, a slightly but constantly decreased cleavage-rate of the SREBP-2-595A-isoform compared to that of the SREBP-2-595G-isoform may lead to a reduced transcriptional activation of the LDL receptor-gene weakening the SREBP-mediated compensation mechanisms, and may, therefore, be a critical factor in the development of polygenic hypercholesterolaemia.

Objective: To consider the relationship between nutrition and aging. To summarize existing knowledge and identify areas of ignorance., Design: Experts from a range of relevant disciplines received and considered a series of questions related to aspects of the topic., Setting: University of Hohenheim, Stuttgart, Germany., Intervention: The experts met and discussed the questions and arrived at a consensus., Conclusion: Many specific conclusions were drawn that support the general view that as we age an inadequate nutrition contributes to the loss of function and the development and progression of disease. Nutritional status is influenced by a range of medical, physiological, psychological, social and situational variables. Adequate nutrition and physical activity are aspects of a health-promoting lifestyle. The encouraging of better nutrition and the taking of exercise is a cost-effective way of decreasing the incidence and progression of age-related disease. The earlier such interventions are introduced the better.

Objective: To determine whether the cystatin C gene (CST3) is genetically associated with late-onset Alzheimer disease (AD)., Design: A case-control study with 2 independent study populations of patients with AD and age-matched, cognitively normal control subjects., Setting: The Alzheimer's Disease Research Unit at the University Hospital Hamburg-Eppendorf, Hamburg, Germany, for the initial study (n = 260). For the independent multicenter study (n = 647), an international consortium that included the Massachusetts Alzheimer's Disease Research Center at the Massachusetts General Hospital, Boston; the Scientific Institute for Research and Patient Care, Brescia, Italy; and Alzheimer's research units at the Universities of Basel and Zurich, Switzerland, and Bonn, Goettingen, and Hamburg, Germany., Participants: Five hundred seventeen patients with AD and 390 control subjects., Measures: Molecular testing of the KspI polymorphisms in the 5' flanking region and exon 1 of CST3 and the apolipoprotein E (APOE) genotype. Mini-Mental State Examination scores for both patients with AD and control subjects., Results: Homozygosity for haplotype B of CST3 was significantly associated with late-onset AD in both study populations, with an odds ratio of 3.8 (95% confidence interval, 1.56-9.25) in the combined data set; heterozygosity was not associated with an increased risk. The odds ratios for CST3 B/B increased from 2.6 in those younger than 75 years to 8.8 for those aged 75 years and older. The association of CST3 B/B with AD was independent of APOE epsilon4; both genotypes independently reduced disease-free survival., Conclusions: CST3 is a susceptibility gene for late-onset AD, especially in patients aged 75 years and older. To our knowledge, CST3 B is the first autosomal recessive risk allele in late-onset AD.

Objectives: We investigated whether apoE genotypes correlate with cognitive functions in clinically healthy persons., Methods: In 1993 and 1995, we measured information processing speed, delayed free recall and semantic aspects of long-term memory in 227 men and 105 women aged 65 and over, a randomly selected subsample of the prospective Basel Study. Cardiovascular risk factors and education were assessed., Results: E2 were more prevalent in old-old (>75 years, 23.5% vs. 15%) compared to E4 than in young-old (<75 years, 19.3% vs. 23.5%). Taking into account age and education, subjects with epsilon3/epsilon4 or epsilon4/epsilon4 alleles (E4) performed lowest in all 3 tests compared to those homozygous for epsilon3 (E3) or carriers of one or two epsilon2 alleles (E2) (reaction time P = 0.009, free recall P = 0.05, WAIS-R vocabulary P<0.05). In old-old there was a significant difference between E2 and E4 for reaction time (P = 0.02) and free recall (P<0.02) but not for vocabulary (P = 0.086). In all 3 groups there were no significant changes after 2 years. The subgroup with the genotype epsilon2/epsilon4 performed consistently best in the cognitive tests. Cholesterol was significantly increased in the E4 and E3 group compared to the E2 group., Conclusion: ApoE genotype correlates with cognitive performance. The increased prevalence of E2 in the old-old and the significantly lower plasma cholesterol levels suggest differential morbidity and mortality as important factors influencing the prevalence of cognitive disorders in late life.

Argyrophilic grain disease (AgD) constitutes one cause of late onset dementia and is histologically characterized by the presence of abundant argyrophilic grains and coiled bodies. Both abnormalities are found mainly in limbic structures, among them the sector CA1 of the hippocampus, the entorhinal cortex, and the amygdala. Using appropriate silver staining techniques, they are easily detectable and can easily be distinguished from neurofibrillary lesions of Alzheimer's disease (i.e., tangles and threads). Although the histopathology of AgD is well characterized, the nosological status is still unclear because most cases of AgD are associated with Alzheimer-type changes. For some authors, therefore, AgD is considered a variant of Alzheimer's disease rather than a distinct disease entity. The present review is aimed at presenting argyrophilic grain disease to a larger readership than just neuropathologists who are interested in neurodegenerative disorders. In this review we summarize morphological, immunohistochemical, clinico-pathological and genetic data obtained in more than 90 subjects with AgD. The main conclusions of this review are that AgD represents one of the most frequent, dementing disorders of old age and that it has to be clearly distinguished from Alzheimer's disease.

Apolipoprotein E (ApoE) genotypes were analyzed in 35 subjects with argyrophilic grain diseases (AgD). Neuropathologically, all cases were characterized by abundant argyrophilic grains in the hippocampus and in the entorhinal or parahippocampal cortex. We found an ApoE epsilon4 allele frequency of 0.007 in AgD patients, which is significantly different from the epsilon4 allele frequencies reported in age-matched Alzheimer's disease (AD) patients (0.24), but not from age-matched controls (0.09). We conclude that the ApoE epsilon4 allele does not constitute a risk factor for the development of AgD. Our results further suggest that AgD is a progressive disorder differentiated from AD by morphological and genetic criteria.

Objective: To determine the short- and long-term effects of resistance training on muscle strength, psychological well-being, control-beliefs, cognitive speed and memory in normally active elderly people., Methods: 46 elderly people (mean age 73.2 years; 18 women and 28 men), were randomly assigned to training and control groups (n=23 each). Pre- and post-tests were administered 1 week before and 1 week after the 8-week training intervention. The training sessions, performed once a week, consisted of a 10 min warm-up phase and eight resistance exercises on machines., Results: There was a significant increase in maximum dynamic strength in the training group. This training effect was associated with a significant decrease in self-attentiveness, which is known to enhance psychological well-being. No significant changes could be observed in control-beliefs. Modest effects on cognitive functioning occurred with the training procedure: although there were no changes in cognitive speed, significant pre/post-changes could be shown in free recall and recognition in the experimental group. A post-test comparison between the experimental group and control group showed a weak effect for recognition but no significant differences in free recall. Significant long-term effects were found in the training group for muscular strength and memory performance (free recall) 1 year later., Conclusion: An 8-week programme of resistance training lessens anxiety and self-attentiveness and improves muscle strength.

In a previous study we reported on a late onset dementia which occurred in only half of the patients with argyrophilic grain disease (AgD) investigated. To find a correlation between the distribution of argyrophilic grains (ArG) and the occurrence of a late onset dementia, we examined the limbic area in 35 subjects who had ArG as the main neuropathological finding. A retrospective clinical analysis was performed by collecting information from hospital charts supplemented by standardized interviews based on DSM IV criteria for dementia. Sections from the rostral and caudal hippocampal regions, including the entorhinal/transentorhinal and parahippocampal cortex on both sides, were strained by the Gallays method. Nineteen subjects were diagnosed as demented according to these criteria; 16 were considered to have been cognitively normal. High numbers of ArG were observed in the anterior part of the CA1 subfield in all cases. However, the posterior half of CA1 was involved significantly more often and more severely in demented than in non-demented individuals (P < 0.01). Moreover, the distribution of ArG in the entorhinal/transentorhinal and parahippocampal cortex was more widespread in the group of demented patients (P < 0.05). These results show that the intellectual status of patients with AgD was related to the extension of ArG in the limbic area. We suggest that AgD is a progressive neurodegenerative disorder with early subclincial lesions in the anterior part of the hippocampal formation. To provide a more accurate clinicopathological correlation, the rostrocaudal extension of ArG in the limbic area should be evaluated in AgD cases.

Mass screening for blood cholesterol as part of routine preventive health care of children continues to be discussed in several countries. Results of longitudinal studies underline the importance of the predictive value of cholesterol levels assessed during childhood. Some countries have changed their recommendations during the past years to blood cholesterol screening for obese children only or for children of high risk families. In the Kindergarten-study Basel, a follow-up study on somatic, psychic and social development of Swiss and immigrant schoolchildren, cardiovascular risk factors were assessed at the ages of 5, 10 and 14 years. The age-specific levels of total and LDL-cholesterol found in our study were slightly higher and HDL-cholesterol lower than, for example, those found in the Bogalusa Heart Study. For total cholesterol no significant tracking correlations over the 5 and 9 year periods were found. Tracking of LDL- and HDL-cholesterol differed between nationalities and sexes. The total cholesterol/HDL-cholesterol index tracked slightly better. Italian girls showed the best 9-year tracking for HDL-cholesterol (r = 0.56). The differences between this and other studies can only partially be explained by different sampling and laboratory methods. Individual changes in cholesterol levels between the ages of 5 and 14 were marked. Sexual maturation was found to be of minor influence. Body mass index was the most consistent risk factor in our population. Changes of sex or growth hormone levels during puberty, but also changes of nutritional habits or physical activity might influence the individual cholesterol levels. Before recommendations on mass screening of cholesterol in children are made, the different longitudinal patterns of changes in cholesterol levels, and subpopulation-specific changes of nutritional habits and physical activity, should be discussed. The results of the Kindergarten study Basel suggest that attention should be paid to screening for obesity and to health education regarding nutrition and physical activity.

The short-term effects of whole milk and milk fermented by Pseudomonas fluorescens, of the amino acid composition of the diet and of feeding frequency on the level of plasma lipids, were investigated in six 1-year-old adult boars. The experimental diets contained equal amounts of protein, carbohydrates, fat and cholesterol. After an adaptation period of 5 d for each experimental treatment, blood was collected at regular intervals during 48 h and plasma levels of cholesterol, triacylglycerol, high-density-lipoprotein (HDL)-cholesterol and low-density-lipoprotein (LDL)-cholesterol were examined. All variables except HDL-cholesterol showed distinct diurnal fluctuations, which were substantially influenced by feeding frequency. Variations in the amino acid composition of the experimental diets, which were within a physiological range, had no effect on the level of plasma lipids. Plasma lipid levels were significantly lower when the animals received the diets containing milk instead of the diet without milk: cholesterol, triacylglycerol, and LDL-cholesterol were reduced by 5.6, 5.8 and 10% respectively (pondered means) while HDL-cholesterol remained unaffected. Fermentation of whole milk by P. fluorescens reduced the lipid-lowering effect. Our findings suggest that the intake of diets containing milk results in a lower plasma cholesterol and LDL-cholesterol level than the intake of diets with a similar nutrient content which do not contain milk.

The accuracy of computed tomography, electroencephalography, and clinical features in the differential diagnosis of senile dementia was studied prospectively. Out of 50 demented patients, autopsy revealed 32 cases with either senile dementia of the Alzheimer's type (SDAT), multi-infarct dementia (MID), or a combination of both. Eighteen patients had dementia caused by other diseases. Based on a combination of computed tomography, electroencephalography, and clinical features, senile dementia of the Alzheimer's type was differentiated from all 50 patients, with a specificity of 83% and a sensitivity of 80%. Focusing on senile dementia of the Alzheimer's type, multi-infarct dementia, or a combination of both, specificity decreased to 65% and sensitivity to 47%. Comparing the different methods, multi-infarct processes were diagnosed with a higher sensitivity by the clinical features (73%) than by computed tomography (18%) or electroencephalography (18%). None of the methods validly differentiated multi-infarct dementia from a combination of multi-infarct dementia and senile dementia of the Alzheimer's type.

The influence of bopindolol monotherapy on blood pressure and plasma lipid fractions was investigated in 24 hypertensive patients. Bopindolol lowered blood pressure and heart rate significantly. When compared with placebo no changes were found in the plasma concentrations of total cholesterol, LDL cholesterol and HDL cholesterol. Plasma triglycerides were significantly increased after 4 and 8 weeks but not after 12 weeks of bopindolol. It is concluded that bopindolol is an effective and well tolerated beta-adrenoceptor blocker in hypertensive patients. The fact that it does not lower HDL cholesterol could be a potential advantage.

The influence of bopindolol monotherapy on blood pressure and plasma lipid fractions was investigated in 24 hypertensive patients. Bopindolol lowered blood pressure and heart rate significantly. When compared with placebo, no changes were found in the plasma concentrations of total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol. Plasma triglycerides were significantly increased after 4 and 8 weeks but not after 12 weeks of bopindolol. It is concluded that bopindolol is an effective and well tolerated beta blocker in hypertensive patients. That it does not lower HDL cholesterol could be a potential advantage.