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Background: Ghrelin, leptin and high-molecular-weight (HMW) adiponectin have been linked to depression in middle-aged adults. Pathophysiological mechanisms of depression change as age progresses and it is unclear whether the same associations exist in older adults.Methods: We analyzed the associations between ghrelin, leptin and HMW adiponectin and depressive symptoms (Center for Epidemiologic Studies Depression (CES-D) score ≥ 16) in a community-dwelling cohort of 898 participants in a multivariable logistic regression analysis at baseline and after three years of follow-up, were applicable stratified by sex, age and waist-hip-ratio (WHR).Results: At baseline no significant associations were found. After three years of follow-up ghrelin was associated with higher odds for depressive symptoms (fully adjusted continuous analysis OR 2.27, 95% CI 1.42 - 3.61). There was effect modification for age and WHR, with significant associations in participants younger than 69.7 years (median) and with a WHR below 0.9554 (mean). In the sex-stratified analysis for leptin we found significant associations in men (fully adjusted continuous analysis OR 1.07, 95% CI 1.02 - 1.12). For HMW adiponectin there were no significant associations in the multivariable analysis.Limitations: As our cohort consisted of relatively healthy participants with intact cognitive function, selection bias may have contributed to lack of significant baseline associations.Conclusions: Our results show significant associations between ghrelin and - for men only - leptin and depressive symptoms after three years of follow up. This may provide a new therapeutic window for treatment of depressive symptoms in older adults, as both ghrelin and leptin are positively influenced by weight loss. [ABSTRACT FROM AUTHOR]

Background: The aim was to investigate the associations of sarcopenia as defined by European Working Group on Sarcopenia in Older People (EWGSOP) and Foundation for the National Institutes of Health (FNIH) Sarcopenia Project, and their underlying components, with the incidence of recurrent falling and fractures.Methods: In 498 older men and women (mean age = 75.2 [SD = 6.4]) from the Longitudinal Aging Study Amsterdam (LASA), the sarcopenia components lean mass (DXA), handgrip strength (handheld dynamometer), and gait speed were measured. Data on falls (3-year follow-up) and fractures (10-year follow-up) were collected. Cox regression analyses were performed, adjusting for age, sex, and total body fat.Results: Recurrent falling occurred in 130 persons and 60 persons experienced a fracture during follow-up. Participants who were identified as sarcopenic based on the FNIH definitions had a more than 2-fold increased risk to become a recurrent faller. There was no association between sarcopenia based on the EWGSOP definition and incidence of recurrent falling. When the sarcopenia components were examined individually, only a low grip strength was associated with incidence of recurrent falling, independent of a low lean mass or a slow gait speed. Sarcopenia according to both definitions was not associated with incident fractures, which may be caused by low statistical power.Conclusion: Sarcopenia according to the FNIH definitions, but not according to the EWGSOP definition was associated with recurrent falling. When examining the individual components, only a low grip strength was independently associated with recurrent falling. No associations between sarcopenia with incidence of fractures were found. [ABSTRACT FROM AUTHOR]

The prevalence of risk factors for falls increases during middle-age, but the prevalence of falls in this age-range is often overlooked and understudied. The aim was to calculate the prevalence of falls in middle-aged adults (aged 40–64 years) from four countries. Data were from four population-based cohort studies from Australia (Australian Longitudinal Study on Women’s Health, n = 10556, 100% women, 51–58 years in 2004), Ireland (The Irish Longitudinal Study on Ageing, n = 4968, 57.5% women, 40–64 years in 2010), the Netherlands (Longitudinal Aging Study Amsterdam, n = 862, 51.6% women, 55–64 years in 2012–13) and Great Britain (MRC National Survey of Health and Development, n = 2821, 50.9% women, 53 years in 1999). In each study, falls assessment was based on recall of any falls in the past year. The prevalence of falls was calculated for the total group, for each country, for men and women separately, and for 5-year age-bands. The prevalence was higher in Australia (27.8%, women only) and the Netherlands (25.1%) than in Ireland (17.6%) and Great Britain (17.8%, p<0.001). Women (27.0%) had higher prevalences than men (15.2%, p<0.001). The prevalence increased from 8.7% in 40–44 year olds to 29.9% in 60–64 year olds in women, and from 14.7% in 45–49 year olds to 15.7% in 60–64 year olds in men. Even within 5-year age-bands, there was substantial variation in prevalence between the four cohorts. Weighting for age, sex and education changed the prevalence estimates by less than 2 percentage points. The sharp increase in prevalence of falls in middle-age, particularly among women supports the notion that falls are not just a problem of old age, and that middle-age may be a critical life stage for preventive interventions. [ABSTRACT FROM AUTHOR]

Background: Unhealthy lifestyle factors, such as obesity, smoking, excessive alcohol consumption and physical inactivity, are associated with increased morbidity and mortality risk, even in older age. We investigated trends in lifestyle among three cohorts of adults aged 55-64 years from the Netherlands. Methods: Data from the Longitudinal Aging Study Amsterdam were used. This study consisted of three randomly selected samples of men and women. Lifestyle data were collected in 1992/1993 (cohort 1, n = 988), in 2002/2003 (cohort 2, n = 1002) and in 2012/2013 (cohort 3, n = 1023). Trends in lifestyle across cohorts were tested using multivariable regression analyses. Results: Complete lifestyle data were available for 834 participants from cohort 1, 861 from cohort 2 and 845 from cohort 3. Among men, but not in women, mean BMI and prevalence of obesity increased over time. The mean minutes per day spent being physically active decreased among both men and women, from 130-107 and 230-122 (1992/1993) to 114-100 and 192-109 (2002/2003), and 126-98 and 187-112 (2012/ 2013), respectively. The percentage of men and women defined as excessive drinkers (>7 alcoholic consumptions per week) increased from 54.9%, 62.3% to 65.4% (men) and 22.7%, 36.1% to 37.4% (women), in 1992/1993, 2002/ 2003 and 2012/2013, respectively. The percentage of non-smoking men and women increased over time. Conclusion: The lifestyle of Dutch adults aged 55-64 years was less healthy in 2012/2013 compared with 2002/ 2003 and 1992/1993. Political attention regarding healthy ageing should target the prevention of overweight, physical inactivity and excessive alcohol consumption in middle-aged persons. [ABSTRACT FROM AUTHOR]

Worldwide, vitamin D deficiency is a common finding. Within individuals 25-hydroxyvitamin D (25OH)D) concentrations remain fairly stable over time although large differences in individual longitudinal changes exist. During aging vitamin D metabolism and activity changes in several different ways. Intestinal resistance to 1,25(OH)2D develops which hampers intestinal calcium uptake. Vitamin D receptor number decreases with aging in several organs involved in calcium metabolism and 1alpha-hydroxylase activity decreases mainly due to a decrease in renal function reducing vitamin D activation. Effects of 1,25(OH)2D on cell proliferation and differentiation may influence potential anti-cancer effects whereas regulation of telomere length may result in longevity. In older individuals, vitamin D supplementation has positive effects on fracture risk, number of falls and physical function. Supplementation in older populations warrants specific attention. Effects on “non-classical” outcomes may be revealed by ongoing large randomized clinical trials with high doses of vitamin D. [ABSTRACT FROM AUTHOR]

Background: Although vitamin D may have both protective and symptomatic effects in Parkinson's disease (PD), the evidence is scarce and not well understood. Also, 25-hydroxyvitamin D (vitamin D) is suggested to play a neuroprotective and neurotrophic role in the brain. Therefore, this review investigates the relationship between vitamin D and PD. Objective: Investigate the evidence for a relationship between vitamin D and PD by summarizing observational and interventional studies in humans, as well as relevant experimental studies. Methods: A systematic search was made in the Medline, Cochrane and Embase databases (from inception to March 2014). All identified titles were independently evaluated by two reviewers. Articles were selected based on the presence of PD-related outcome data. Included were observational studies (including genetic studies) and interventional studies in humans, as well as relevant animal studies. Results: A total of 20 studies (14 observational, 1 interventional and 5 rodent studies) were selected for analysis. Eight observational studies showed that serum 25(OH) D levels tend to be low in PD. One observational study indicated that low serum 25(OH) D may worsen automatic postural responses and one interventional study suggested that vitamin D supplementation can prevent worsening (based on the Hoehn and Yahr rating scale). Studies in rodent models of PD showed a protective effect of vitamin D treatment on dopaminergic neurons in the substantia nigra. Results of genetic studies on the association between vitamin D receptor polymorphisms and the risk of PD were contradictory. Conclusion: The literature supports possible protective and symptomatic effects of vitamin D in PD. However, more observational and interventional studies in humans are needed to confirm and further elucidate the suggested beneficial effect of vitamin D on PD. [ABSTRACT FROM AUTHOR]

Objectives Elevated systemic levels of pro-inflammatory cytokines involved in the pathogenesis of osteoporosis. Our objective was to investigate whether low grade systemic inflammation was associated with bone markers, bone quality, bone mass and fracture risk in a population of older persons. Methods Serum interleukin 6 (IL-6), high-sensitivity C-reactive protein (hsCRP) and erythrocyte sedimentation rate (ESR) were measured in 1287 participants of the Longitudinal Aging Study Amsterdam (LASA), a population based study in a representative sample of older men and women (age 76 ± 6.7 years). Bone quality was measured by quantitative ultrasound measurements (QUS) at baseline and after 3 years at the calcaneus, and bone mineral density was measured by dual-energy X-ray absorptiometry (DXA) at the spine and hip in a subpopulation. Furthermore, the bone markers osteocalcin (OC) and urinary excretion of deoxypyridinoline (DPD) were determined. Incident clinical fractures were recorded during 6 years of follow-up. Results Multivariable regression analyses revealed higher IL-6 and ESR levels were associated with lower quantitative ultrasound values in older men (β = − 0.98; 95% CI − 57.72 to − 6.42, p < 0.05) and (β = − 0.221; 95% CI − 15.39 to − 3.27, p < 0.05) respectively at baseline, but not in women. No significant associations were found between inflammatory markers and bone markers, bone loss at the spine or hips, fracture rate or time to fracture. Conclusion Elevated inflammatory markers are associated with impaired bone quality in older men, but not in women. No associations were found with the risk for fractures. [ABSTRACT FROM AUTHOR]

Objective: The role of osteocalcin (OC) in cardiovascular disease (CVD) is unresolved. We aimed to study the association between plasma OC concentrations and the risk of non-fatal and fatal CVDs. We also aimed to investigate whether such an association, if present, would be mediated by established metabolic risk factors. Design: A population-based longitudinal cohort study. Methods: In 1995/1996, OC was determined in blood samples drawn from 1319 subjects aged 65-88 years participating in the Longitudinal Aging Study Amsterdam in 1995/1996. The self-reported CVD events were collected every 3 years until 2005/2006, and CVD deaths until 1st January 2007. Cox proportional hazards regression was performed, considering potential confounders (smoking, physical activity, and BMI) and mediators (blood pressure, plasma triglycerides, total and HDL cholesterol, fructosamine, and aortic calcification). Results: During the median 4.1 years follow-up, 709 subjects (53.8%) suffered a CVD event. There was no overall association betweenOCandCVD: hazard ratio (HR)was 0.97 (95%CI 0.90-1.04) per nmol/l higherplasmaOC, adjusted for age and sex. There was a statistical interaction between plasmaOC, age, and sex on CVD (PZ0.014). In those subjects agedR≥75 years, age-adjusted HRs (95%CI)were 0.86 (0.75-0.99) inmen and 1.16 (1.03-1.31) inwomen pernmol/l higher plasmaOC.Adjustment for covariates only slightly attenuated the association in older-old men, but did not affect the association in older-old women. Conclusion: A higher plasma OC concentration was associated with a reduced risk of CVD in older-old men and with an increased risk of CVD in older-old women. We found no evidence that this was mediated by arterial calcification or metabolic risk factors. [ABSTRACT FROM AUTHOR]

Vitamin D status can be assessed by measuring concentrations of 25-hydroxyvitamin D (25(OH)D). Sunlight is the most important source of vitamin D and stimulates the production of vitamin D3 in the skin during the summer, depending on age, skin pigmentation, clothing style, and sunscreen use. Seasonal variation in serum 25(OH)D is between 10 and 20 nmol/L in adults and almost absent in nursing home residents. Sunscreen use decreases, but does not abolish, vitamin D production in the skin. Clothing style has a large influence on vitamin D production. Furthermore, vitamin D status can be improved by ingestion of fatty fish and the fortification of milk or orange juice. A high dietary calcium intake has a vitamin D-sparing effect, because it increases the half-life of 25(OH)D. A combination of sunlight exposure, nutrition, food fortification, and supplements is desirable to obtain sufficient vitamin D status in the population of most countries throughout the year. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Vitamin K plays a pivotal role in the synthesis of Matrix Gla protein (MGP), a calcification inhibitor in vascular tissue. Vascular calcification has become an important predictor of cardiovascular disease. The aim of the current study was to examine the potential association of circulating desphospho-carboxylated and -uncarboxylated MGP (dp-cMGP and dp-ucMGP), reflecting vitamin K status, with the incidence of cardiovascular events and disease (CVD) in older individuals. Study design: The study was conducted in 577 community-dwelling older men and women of the Longitudinal Aging Study Amsterdam (LASA), aged >55 year, who were free of cardiovascular disease at baseline. Multivariate Cox proportional hazards models were used to analyze the data. Main outcome measures: Incidence of CVD. Results: After a mean follow-up of 5.6±1.2 year, we identified 40 incident cases of CVD. After adjustment for classical confounders and vitamin D status, we observed a more than 2-fold significantly higher risk of CVD for the highest tertile of dp-ucMGP with a HR of 2.69 (95% CI, 1.09–6.62) as compared with the lowest tertile. Plasma dp-cMGP was not associated with the risk of CVD. Conclusions: Vitamin K insufficiency, as assessed by high plasma dp-ucMGP concentrations is associated with an increased risk for cardiovascular disease independent of classical risk factors and vitamin D status. Larger epidemiological studies on dp-ucMGP and CVD incidence are needed followed by clinical trials to test whether vitamin K-rich diets will lead to a decreased risk for cardiovascular events. [Copyright &y& Elsevier]

Objective The prevalence of both low testosterone levels and depression increases with age. Currently, there is no consensus regarding the existence of an association. Our study analyses the cross-sectional association of testosterone levels with depressive symptoms and its prospective association with the development of incident depressive symptoms. Design Longitudinal population-based study; based on the data of the Longitudinal Aging Study Amsterdam (LASA) including 608 men aged ≥65 years (median age 75·6 years). Measurements Linear and logistic regression between total and free testosterone levels and depressive symptoms as measured by the Center of Epidemiologic Studies Depression (CES-D) scale, taking into account medical and lifestyle factors. Cox Proportional Hazards model was used to assess incident depressive symptoms. Results Unadjusted linear regression between square-root transformed CES-D scores and free testosterone levels showed a significant inverse association as a continuous variable (β = −0·10, P < 0·05), lowest quartile compared to highest (β = 0·12, P < 0·05) and with a threshold value of 170 pmol/l (β = 0·13, P < 0·05). The results remained significant for the group below threshold after adjustment for all confounders (β = 0·09, P < 0·05). Cox Proportional Hazards Model showed a decreased risk for incident depressive symptoms for men with higher free testosterone levels [HR = 0·997 CI (0·995–1·000)]. Men with the threshold value below 220 pmol/l were at increased risk of incident depressive symptoms [HR = 1·989 CI (1·173–3·374)]. Conclusions Free testosterone levels below 170 pmol/l are associated with depressive symptoms, while free testosterone levels below 220 pmol/l (lowest quintile of our population) predict the onset of depressive symptoms. [ABSTRACT FROM AUTHOR]

Objective Sex steroids play an important role in the maintenance of bone health. Association studies on sex steroids and fractures are not consistent. Our objective was to examine whether serum oestradiol (E2) and testosterone (T) are associated with quantitative ultrasound (QUS), bone mineral density (BMD), bone turnover markers and fracture incidence. Design The Longitudinal Ageing Study Amsterdam (LASA), an ongoing cohort study including 623 men and 634 women, aged 65–88 years. Measurements Serum levels of E2, T, SHBG, albumin, bone turnover markers serum osteocalcin (OC) and urinary deoxypyridinoline (DPD/Cr) were measured. QUS of the heel and BMD of the hip were assessed, and a 6-year fracture follow-up was performed. Results Men in the lowest quartile (Q1) of bioavailable E2 (bioE2) had higher levels of bone turnover and lower BMD ( B = –0·09, P < 0·01) and QUS than men in the highest quartile (Q4). This also applied to Q1 of bioT. Women in Q1 of bioE2 had higher levels of bone turnover and lower BMD ( B = –0·07, P < 0·01) and QUS than women in Q4. In men and women, levels of bioE2 below the median were associated with an increased risk of osteoporotic fractures after all adjustments [hazard ratio (HR) 1·53, 95% confidence interval (CI) 1·02–2·29]. In men, univariate analysis revealed that low bioT was associated with an increased fracture risk (HR 1·91, 95% CI 1·03–3·56), but after adjustment for age, this association was no longer significant. Conclusions Low levels of bioE2 and bioT were found to be associated with high bone turnover, low QUS and BMD and high risk of osteoporotic fractures in both men and women. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To estimate the maximum potential preventive effect of hip protectors in older persons living in the community or homes for the elderly. DESIGN: Observational cohort study. SETTING: Emergency departments in the Netherlands. PARTICIPANTS: Hip fracture patients aged 70 and older who visited the emergency departments of five hospitals in the Netherlands (n=520). MEASUREMENTS: Using the risk score of the Dutch Guidelines for Osteoporosis, how many patients had a high risk for fractures was retrospectively assessed. In addition, the circumstances of the hip fracture were assessed (n=299). Four factors were specified that might influence the maximum potential preventive effect of hip protectors: (1) hip fracture occurred in persons having a low risk, (2) hip fracture was not the consequence of a fall, (3) hip fracture occurred during circumstances that preclude the use of hip protectors, and (4) hip fracture occurred during the night. RESULTS: When providing hip protectors to women at high risk of fractures, 48.2% of all hip fractures could have been prevented. CONCLUSION: Many hip fractures occur in persons with a low risk for hip fracture or under circumstances that preclude the use of hip protectors. It was estimated that the maximum potential preventive effect of hip protectors is approximately 50% in older women living in the community or homes for the elderly. The actual preventive effect will be lower and depends on the acceptance and effectiveness of hip protectors and adherence to wearing them. [ABSTRACT FROM AUTHOR]

Complaints regarding, and morbidity of, osteoporosis are caused by fractures which are associated with pain and decrease of physical function, social function, and well-being. These are aspects of quality of life. Health-related quality of life covers physical, mental, and social well-being. Quality of life may be measured for evaluation of treatment effects in clinical trials, for the assessment of the burden of the disease of osteoporosis, and for estimates of the cost-effectiveness of different treatment scenarios in health care policy. Quality of life has been measured in patients with osteoporosis with generic questionnaires such as SF-36 and EQ-5D, which can be used in many diseases, or with one of the six available osteoporotic-specific questionnaires, e.g., Qualeffo-41 or OPAQ. Every questionnaire has to be validated to assess psychometric properties and discrimination power between patients with osteoporosis and control subjects. The value attached to specific health states (utility) can be assessed with some generic instruments or by systematic questioning of the patient, e.g., the time-trade-off method. This results in one value for health status ranging from 0 (death) to 1 (perfect health). Utility values can be used to calculate loss of quality-adjusted life years (QALY). Most data have been obtained in patients with prevalent vertebral fractures. Scores of specific and generic questionnaires showed significant loss of quality of life with prevalent vertebral fractures. In addition, studies with Qualeffo-41 and OPAQ showed a deteriorating quality of life with increasing number of vertebral fractures. Lumbar fractures had more impact on quality of life than thoracic fractures. Incident vertebral fractures were also associated with a decrease of quality of life especially in the physical function domain. This applied to clinical incident vertebral fractures as well as to subclinical fractures to a lesser degree. Loss of quality of life following hip fracture has been documented with generic and osteoporosis-specific questionnaires. A considerable loss was observed in the 1st year with some improvement in the 2nd year, but not to baseline values. Quality of life depended on comorbidity, mobility, activities of daily life (ADL)-independence, and fracture complaints. Utility loss has been observed following hip fracture, especially disabling hip fracture, hip and vertebral fracture combined, or multiple vertebral fractures. Utility following osteoporotic fractures has been valued by patients, the healthy elderly, and panels of experts. The healthy elderly gave the worse quality-of-life scores (lower utility) to various hip fractures than patients with hip fractures themselves. In conclusion, suitable instruments exist for measuring quality of life in patients with osteoporotic fractures. These instruments are useful for clinical trials and for assessment of the burden of disease. [ABSTRACT FROM AUTHOR]

A randomized controlled trial was performed to examine the cost-effectiveness of external hip protectors in the prevention of hip fractures. Since the hip protectors were not effective in preventing hip fractures in our study, the main objective became to examine whether the use of hip protectors results in lower average costs per participant in the hip protector group as compared with the control group. In addition, the average costs of a hip fracture and subsequent rehabilitation in frail, institutionalized elderly were calculated. Residents from apartment houses for the elderly, homes for the elderly and nursing homes with a high risk for hip fractures were randomized to the hip protector group (n=276) or control group (n=285). Costs were calculated for the hip fracture and subsequent rehabilitation until 1 year after the fracture. Six months after each hip fracture, a nurse was interviewed and after 12 months, a questionnaire was sent to the general practitioner or nursing home physician to determine the utilization of health care resources. Differences in costs between the groups were analyzed using non-parametric bootstrapping. Eighteen hip fractures occurred in the intervention group and 20 hip fractures (in 19 persons) in the control group (log rankP-value=0.86). The average costs per participant, including the costs of the intervention, were €913 in the intervention group and €502 in the control group (cost difference of €-411; 95% confidence interval: -723; 57). The average costs of a hip fracture and subsequent rehabilitation were €8100 (95% CI: 6716-10,010). The use of hip protectors was not associated with lower costs. In addition, the average costs of a hip fracture and subsequent rehabilitation in the first year after the fracture were estimated at €8100 in institutionalized elderly. [ABSTRACT FROM AUTHOR]

Context: Several randomized controlled trials have been performed to examine the effectiveness of external hip protectors in reducing the incidence of hip fractures, but the results are controversial. Objective: To examine the effectiveness of hip protectors in reducing the incidence of hip fractures in an elderly high-risk population. Design, Setting, and Participants: Randomized controlled trial of elderly persons aged 70 years or older, who have low bone density, and are at high risk for falls. Participants lived in apartment houses for the elderly, homes for the elderly, and nursing homes in Amsterdam and surrounding areas in the Netherlands. They were enrolled in the study between March 1999 and March 2001; the mean follow-up was 69.6 weeks. Of the 830 persons who were screened, 561 persons were enrolled. Intervention: External hip protector. Both groups received written information on bone health and risk factors for falls. Main Outcome Measure: Time to first hip fracture. Survival analysis was used to include all participants for the time they participated. Results: In the intervention group, 18 hip fractures occurred vs 20 in the control group. Four hip fractures in the intervention group occurred while an individual was wearing a hip protector. At least 4 hip fractures in the intervention group occurred late at night or early in the morning. Both in univariate analysis (log-rank P = .86) and in multivariate analysis (hazard ratio [HR], 1.05; 95% confidence interval [CI], 0.55-2.03), no statistically significant difference between the intervention group and control group was found with regard to time to first hip fracture. In addition, the per protocol analysis in compliant participants did not show a statistically significant difference between the groups (HR, 0.77; 95% CI, 0.25-2.38). Conclusion: The hip protector studied was not effective in preventing hip fractures. [ABSTRACT FROM AUTHOR]

It is not clear which specific cognitive function is strongest related to falls. To investigate this, not only “general cognitive functioning,” but also “nonverbal and abstract reasoning,” “information processing speed,” and “immediate memory” were related to falls. Furthermore, relevant effect modifiers, confounders, and mediators were identified. This study was performed within the Longitudinal Aging Study Amsterdam (LASA), a multidisciplinary, prospective cohort study. In this study (n = 1437), an interaction between “immediate memory” and age was found. In persons aged 75 years and over, “immediate memory,” as measured by the 15 Words Test, showed to be an independent risk factor for falls. Part of this relationship was explained by the mediating effects of activity, mobility, and grip strength. The association between the other cognitive functions and falls was only statistically significant in univariate analysis. We conclude that “immediate memory” is an independent risk factor for recurrent falls in persons aged 75 years and older. [Copyright &y& Elsevier]

Before being used in clinical practice, a prediction model should be tested in patients whose data were not used in model development. Previously, we developed the AD F ICE_IT models for predicting any fall and recurrent falls, referred as Any_fall and Recur_fall. In this study, we externally validated the models and compared their clinical value to a practical screening strategy where patients are screened for falls history alone. Retrospective, combined analysis of 2 prospective cohorts. Data were included of 1125 patients (aged ≥65 years) who visited the geriatrics department or the emergency department. We evaluated the models' discrimination using the C-statistic. Models were updated using logistic regression if calibration intercept or slope values deviated significantly from their ideal values. Decision curve analysis was applied to compare the models' clinical value (ie, net benefit) against that of falls history for different decision thresholds. During the 1-year follow-up, 428 participants (42.7%) endured 1 or more falls, and 224 participants (23.1%) endured a recurrent fall (≥2 falls). C-statistic values were 0.66 (95% CI 0.63-0.69) and 0.69 (95% CI 0.65-0.72) for the Any_fall and Recur_fall models, respectively. Any_fall overestimated the fall risk and we therefore updated only its intercept whereas Recur_fall showed good calibration and required no update. Compared with falls history, Any_fall and Recur_fall showed greater net benefit for decision thresholds of 35% to 60% and 15% to 45%, respectively. The models performed similarly in this data set of geriatric outpatients as in the development sample. This suggests that fall-risk assessment tools that were developed in community-dwelling older adults may perform well in geriatric outpatients. We found that in geriatric outpatients the models have greater clinical value across a wide range of decision thresholds compared with screening for falls history alone. [ABSTRACT FROM AUTHOR]

Background: Depressive symptoms and decreased physical functioning are interrelated conditions and common in older persons, causing significant individual and societal burden. Evidence suggests that vitamin D supplementation may be. beneficial for both mental and physical functioning. However, previous randomized controlled trials have yielded inconsistent results and often had suboptimal designs. This study examines the effect of vitamin D supplementation on both depressive symptoms and physical functioning in a high-risk population of older persons with low vitamin D status. Methods/design: The D-Vitaal study is a randomized, double-blind, placebo-controlled trial investigating the effects of a daily dose of 1200 IU vitamin D3 versus placebo for one year on depressive symptoms and physical functioning (primary outcomes) in older adults. Participants (N = 155, age 60-80 years) were recruited from the general population. Eligibility criteria included the presence of depressive symptoms, =1 functional limitation and serum 25-hydroxyvitamin D levels between 15 and 50/70 nmol/L (depending on season). Secondary outcomes include incidence of major depressive disorder, anxiety symptoms, health-related quality of life, cognitive function and cost-effectiveness of the intervention. Discussion: With this study, we aim to elucidate the effects of vitamin D supplementation on depressive symptoms and physical functioning in older persons who are at high risk of developing more substantial mental and physical problems. If effective, vitamin D supplementation can be a preventive intervention strategy that is easy to implement in the primary care setting. [ABSTRACT FROM AUTHOR]

Background: Falls are the leading cause of injury-related mortality and hospitalization among adults aged ≥ 65 years. An important modifiable fall-risk factor is use of fall-risk increasing drugs (FRIDs). However, deprescribing is not always attempted or performed successfully. The ADFICE_IT trial evaluates the combined use of a clinical decision support system (CDSS) and a patient portal for optimizing the deprescribing of FRIDs in older fallers. The intervention aims to optimize and enhance shared decision making (SDM) and consequently prevent injurious falls and reduce healthcare-related costs. Methods: A multicenter, cluster-randomized controlled trial with process evaluation will be conducted among hospitals in the Netherlands. We aim to include 856 individuals aged ≥ 65 years that visit the falls clinic due to a fall. The intervention comprises the combined use of a CDSS and a patient portal. The CDSS provides guideline-based advice with regard to deprescribing and an individual fall-risk estimation, as calculated by an embedded prediction model. The patient portal provides educational information and a summary of the patient's consultation. Hospitals in the control arm will provide care-as-usual. Fall-calendars will be used for measuring the time to first injurious fall (primary outcome) and secondary fall outcomes during one year. Other measurements will be conducted at baseline, 3, 6, and 12 months and include quality of life, cost-effectiveness, feasibility, and shared decision-making measures. Data will be analyzed according to the intention-to-treat principle. Difference in time to injurious fall between the intervention and control group will be analyzed using multilevel Cox regression. Discussion: The findings of this study will add valuable insights about how digital health informatics tools that target physicians and older adults can optimize deprescribing and support SDM. We expect the CDSS and patient portal to aid in deprescribing of FRIDs, resulting in a reduction in falls and related injuries. Trial registration: ClinicalTrials.gov NCT05449470 (7-7-2022). [ABSTRACT FROM AUTHOR]

Objectives: The metabolic syndrome has been associated with a variety of individual variables, including demographics, lifestyle, clinical measures and physical performance. We aimed to identify independent predictors of the prevalence and incidence of metabolic syndrome in a large cohort of older adults. Methods: The Longitudinal Aging Study Amsterdam is a prospective cohort including community-dwelling adults aged 55–85 years. Metabolic syndrome was defined according to criteria of the National Cholesterol Education Program Adult Treatment Panel III. The incidence of metabolic syndrome was calculated over a period of three years. Stepwise backward logistic regression analyses were used to identify predictors, including variables for demographics, lifestyle, clinical measures and physical performance, both in a cross-sectional cohort (n = 1292) and a longitudinal sub-cohort (n = 218). Results: Prevalence and incidence of metabolic syndrome were 37% (n = 479) and 30% (n = 66), respectively. Cross-sectionally, heart disease (OR: 1.91, 95% CI: 1.37–2.65), peripheral artery disease (OR: 2.13, 95% CI: 1.32–3.42), diabetes (OR: 4.74, 95% CI: 2.65–8.48), cerebrovascular accident (OR: 1.92, 95% CI: 1.09–3.37), and a higher Body Mass Index (OR: 1.32, 95% CI: 1.26–1.38) were significant independent predictors of metabolic syndrome. Longitudinally, Body Mass Index (OR: 1.16, 95% CI: 1.05–1.27) was an independent predictor of metabolic syndrome. Conclusion: Four age related diseases and a higher Body Mass Index were the only predictors of metabolic syndrome in the cross-sectional cohort, despite the large variety of variables included in the multivariable analysis. In the longitudinal sub-cohort, a higher Body Mass Index was predictive of developing metabolic syndrome. [ABSTRACT FROM AUTHOR]

Adequate information on oral anticancer agent (OACA) use is an essential element of optimal cancer care. The present study aimed to get insight into the experiences of patients with information on OACA treatment and their characteristics regarding information dissatisfaction. Patients of four Dutch university hospitals using OACA participated in this observational study and completed the Satisfaction with Information about Medicines Scale (SIMS), EORTC Quality of Life Questionnaire-C30, Brief Illness Perception Questionnaire, and Beliefs about Medicines Questionnaire-Specific. Logistic regression analyses were used to determine factors associated with dissatisfaction with information. Patients (n = 208) using capecitabine (35%), lenalidomide (15%), imatinib (14%), temozolomide (12%), sunitinib (11%), thalidomide (5%), dasatinib (4%), erlotinib (2%), and nilotinib (2%) participated. Information on the following SIMS-items was inadequate: how OACA elicit their effect, how long it takes before treatment works, how to conclude that treatment is effective, the risk of side effects and its management, interference with sex life, drowsiness, interference with other medication and alcohol and what to do in case of a missed dose. Younger age, hematological malignancy, dyspnoea, positive perception of consequences of the cancer, low perception of treatment control, and indifferent attitude towards OACA were associated with dissatisfaction with information. In conclusion, a considerable number of patients would have appreciated receiving more information on specific issues relating to the consequences of OACA treatment such as the effects and side effects of OACA and the interference of treatment with various aspects of their daily life. Oncologists, hematologists, lung-oncologists and pharmacists may reconsider the provision of information on OACA treatment. [ABSTRACT FROM AUTHOR]

Several publications have reported on the pre-analytical stability of fibroblast growth factor 23 (FGF23) and some recommend coating blood collecting tubes with protease inhibitors, in order to prevent degradation. These recommendations are based on observations for a first generation assay for the measurement of intact FGF23. However, if this also applies for the contemporary immunoassays, and at what stage of pre-analysis, is unknown. We reviewed data from these previous reports on the issue of FGF23 stability and complemented these findings with data from novel experiments. We concluded that the contemporary intact FGF23 assays by Immutopics, Kainos, Millipore and DiaSorin do not suffer from immediate loss of FGF23 signal and do not require blood withdrawal in protease inhibitor-coated collecting tubes. Nevertheless, FGF23 concentrations do decline when centrifugation is delayed up to 8 h and prompt centrifugation is therefore advised. • None of the contemporary intact FGF23 immunoassays suffer from immediate loss of FGF23 signal. • With the contemporary immunoassays there is no need to coat blood collecting tubes with protease inhibitors. • Prompt centrifugation is advised as signal declines if centrifugation is delayed. [ABSTRACT FROM AUTHOR]

Background: We investigated prospectively among community-dwelling older adults aged 65 years and older whether a larger kyphosis angle is associated with poorer physical performance (balance, muscle strength, or both), and whether this association is unidirectional.Methods: Male and female participants performed a multicomponent physical performance test with subscores for gait, muscle strength, and balance at baseline and after 2 years. Hand grip strength was also measured at baseline and at follow-up. The Cobb angle was measured on DXA-based Vertebral Fracture Assessments, made at the baseline and follow-up visit. Through linear and logistic regression analysis, we investigated the association between the kyphosis angle and physical performance and vice versa. We stratified for sex, and tested for effect modification by age and study center.Results: The mean kyphosis angle was 37° and 15% of the participants (n = 1 220, mean age 72.9 ± 5.7 years) had hyperkyphosis (Cobb angle ≥50°). A larger kyphosis angle at baseline was independently associated with a poorer total physical performance score in women of the oldest quartile (≥77 years) in both the cross-sectional and longitudinal analyses (baseline B -0.32, 95% confidence interval [CI] -0.56-0.08; follow-up B 0.32, 95% CI -0.55-0.10). There was no association between physical performance at baseline and kyphosis progression.Conclusion: A larger kyphosis angle is independently associated with a poorer physical performance at baseline and over time, and the direction of this association is unidirectional. These results emphasize the importance of early detection and treatment of hyperkyphosis to prevent further worsening of the kyphosis angle, thereby potentially preserving physical performance. [ABSTRACT FROM AUTHOR]

Objectives: To assess whether (i) high-intensity resistance training (RT) leads to increased muscle strength compared to low-intensity RT in patients with knee osteoarthritis (OA); and (ii) RT with vitamin D supplementation leads to increased muscle strength compared to placebo in a subgroup with vitamin D deficiency. Design: Randomized controlled trial Setting: Outpatient rehabilitation centre Subjects: Patients with knee OA Interventions: 12 weeks of RT at high-intensity RT (70–80% of 1-repetition maximum (1-RM)) or low-intensity RT (40–50% of 1-RM) and 24 weeks of vitamin D (1200 International units vitamin D3 per day) or placebo supplementation. Main measures: Primary outcome measure was isokinetic muscle strength. Other outcome measure for muscle strength was the estimated 1-RM. Secondary outcome measures were knee pain and physical functioning. Results: 177 participants with a mean age of 67.6 ± 5.8 years were included, of whom 50 had vitamin D deficiency. Isokinetic muscle strength (in Newton metre per kilogram bodyweight) at start, end and 24 weeks after the RT was 0.98 ± 0.40, 1.11 ± 0.40, 1.09 ± 0.42 in the high-intensity group and 1.02 ± 0.41, 1.15 ± 0.42, 1.12 ± 0.40 in the low-intensity group, respectively. No differences were found between the groups, except for the estimated 1-RM in favour of the high-intensity group. In the subgroup with vitamin D deficiency, no difference on isokinetic muscle strength was found between the vitamin D and placebo group. Conclusions: High-intensity RT did not result in greater improvements in isokinetic muscle strength, pain and physical functioning compared to low-intensity RT in knee OA, but was well tolerated. Therefore these results suggest that either intensity of resistance training could be utilised in exercise programmes for patients with knee osteoarthritis. No synergistic effect of vitamin D supplementation and RT was found, but this finding was based on underpowered data. [ABSTRACT FROM AUTHOR]

Background: Fibrodysplasia Ossificans Progressiva (FOP) is a genetic, progressive and devastating disease characterized by severe heterotopic ossification (HO), loss of mobility and early death. There are no FDA approved medications. The STOPFOP team identified AZD0530 (saracatinib) as a potent inhibitor of the ALK2/ACVR1-kinase which is the causative gene for this rare bone disease. AZD0530 was proven to prevent HO formation in FOP mouse models. The STOPFOP trial investigates the repositioning of AZD0530, originally developed for ovarian cancer treatment, to treat patients with FOP.Methods: The STOPFOP trial is a phase 2a study. It is designed as a European, multicentre, 6-month double blind randomized controlled trial of AZD0530 versus placebo, followed by a 12-month trial comparing open-label extended AZD0530 treatment with natural history data as a control. Enrollment will include 20 FOP patients, aged 18-65 years, with the classic FOP mutation (ALK2 R206H). The primary endpoint is objective change in heterotopic bone volume measured by low-dose whole-body computer tomography (CT) in the RCT phase. Secondary endpoints include 18F NaF PET activity and patient reported outcome measures.Discussion: Clinical trials in rare diseases with limited study populations pose unique challenges. An ideal solution for limiting risks in early clinical studies is drug repositioning - using existing clinical molecules for new disease indications. Using existing assets may also allow a more fluid transition into clinical practice. With positive study outcome, AZD0530 may provide a therapy for FOP that can be rapidly progressed due to the availability of existing safety data from 28 registered clinical trials with AZD0530 involving over 600 patients.Trial Registration: EudraCT, 2019-003324-20. Registered 16 October 2019, https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-003324-20/NL .Clinicaltrials: gov , NCT04307953 . Registered 13 March 2020. [ABSTRACT FROM AUTHOR]

Summary: Hyperkyphosis, an increased kyphosis angle of the thoracic spine, was associated with a higher fall incidence in the oldest quartile of a large prospective cohort of community-dwelling older adults. Hyperkyphosis could serve as an indicator of an increased fall risk as well as a treatable condition. Introduction: Hyperkyphosis is frequently found in adults aged 65 years and older and may be associated with falls. We aimed to investigate prospectively in community-dwelling older adults whether hyperkyphosis or change in the kyphosis angle is associated with fall incidence. Methods.: Community-dwelling older adults (n = 1220, mean age 72.9 ± 5.7 years) reported falls weekly over 2 years. We measured thoracic kyphosis through the Cobb angle between the fourth and 12th thoracic vertebra on DXA-based vertebral fracture assessments and defined hyperkyphosis as a Cobb angle ≥ 50°. The change in the Cobb angle during follow-up was dichotomized (< 5 or ≥ 5°). Through multifactorial regression analysis, we investigated the association between the kyphosis angle and falls. Results: Hyperkyphosis was present in 15% of the participants. During follow-up, 48% of the participants fell at least once. In the total study population, hyperkyphosis was not associated with the number of falls (adjusted IRR 1.12, 95% CI 0.91–1.39). We observed effect modification by age (p = 0.002). In the oldest quartile, aged 77 years and older, hyperkyphosis was prospectively associated with a higher number of falls (adjusted IRR 1.67, 95% CI 1.14–2.45). Change in the kyphosis angle was not associated with fall incidence. Conclusions: Hyperkyphosis was associated with a higher fall incidence in the oldest quartile of a large prospective cohort of community-dwelling older adults. Because hyperkyphosis is a partially reversible condition, we recommend investigating whether hyperkyphosis is one of the causes of falls and whether a decrease in the kyphosis angle may contribute to fall prevention. [ABSTRACT FROM AUTHOR]

Objective: High as well as low levels of IGF1 have been associated with cardiovascular diseases (CVD). The relationship of IGF1 with (components of) the metabolic syndrome could help to clarify this controversy. The aims of this studywere: i) to investigate the association of IGF1 concentration with prevalent (components of) the metabolic syndrome; and ii) to examine the role of (components of) the metabolic syndrome in the relationship between IGF1 and incident CVD during 11 years of follow-up. Methods: Data were used from the Longitudinal Aging Study Amsterdam, a cohort study in a representative sample of the Dutch older population (⩾65 years). Datawere available in 1258 subjects. Metabolic syndrome was determined using the definition of the US National Cholesterol Education Program Adult Treatment Panel III. CVD were ascertained by self-reports and mortality data. Results: Levels of IGF1 in the fourth quintile were associated with prevalent metabolic syndrome compared with the lowest quintile (odds ratio: 1.59, 95% confidence interval (CI) 1.09-2.33). The middle up to the highest quintile of IGF1 was positively associated with high triglycerides in women. Metabolic syndrome was not a mediator in the U-shaped relationship of IGF1 with CVD. Both subjects without the metabolic syndrome and low IGF1 levels (hazard ratio (HR) 1.75, 95% CI 1.12-2.71) and subjects with the metabolic syndrome and high IGF1 levels (HR 2.28, 95% CI 1.21-4.28) demonstrated increased risks of CVD. Conclusions: In older people, high-normal IGF1 levels are associated with prevalent metabolic syndrome and high triglycerides. Furthermore, this study suggests the presence of different pathomechanisms for both low and high IGF1 levels and incident CVD [ABSTRACT FROM AUTHOR]

Objective: To what extent endogenous subclinical thyroid disorders contribute to impaired physical and cognitive function, depression, and mortality in older individuals remains a matter of debate. Design: A population-based, prospective cohort of the Longitudinal Aging Study Amsterdam. Methods: TSH and, if necessary, thyroxine and triiodothyronine levels were measured in individuals aged 65 years or older. Participants were classified according to clinical categories of thyroid function. Participants with overt thyroid disease or use of thyroid medication were excluded, leaving 1219 participants for analyses. Outcome measures were physical and cognitive function, depressive symptoms (cross-sectional), and mortality (longitudinal) Results: Sixty-four (5.3%) individuals had subclinical hypothyroidism and 34 (2.8%) individuals had subclinical hyperthyroidism. Compared with euthyroidism (n=1121), subclinical hypo-, and hyperthyroidism were not significantly associated with impairment of physical or cognitive function, or depression. On the contrary, participants with subclinical hypothyroidism did less often report more than one activity limitation (odds ratio 0.44, 95% confidence interval (CI) 0.22-0.86). After a median follow-up of 10.7 years, 601 participants were deceased. Subclinical hypo- and hyper-thyroidism were not associated with increased overall mortality risk (hazard ratio 0.89, 95% CI 0.59-1.35 and 0.69, 95% CI 0.40-1.20 respectively). Conclusions: This study does not support disadvantageous effects of subclinical thyroid disorders on physical or cognitive function, depression, or mortality in an older population. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The fall risk profile developed in the Longitudinal Aging Study Amsterdam (LASA) identifies community-dwelling elderly at high risk for recurrent falling. This study assessed the predictive validity of this profile in older persons seeking care after a fall. Study Design and Setting: The LASA fall risk profile was completed for 408 persons of 65 years and older who consulted the emergency department or general practitioner after a fall. Falls were prospectively reported with a calendar during 1 year. Recurrent falling was defined as ≥2 falls within a period of 6 months. Results: During 1 year of followup, 76 (18.6%) participants became recurrent fallers. The area under the receiver operating characteristic curve was 0.65 (95% confidence interval [95% CI]: 0.58–0.72). At a cutoff value of 8, the sensitivity was 56.6% (CI: 51.8–61.4), the specificity was 71.4% (CI: 67.0–75.8), the positive predictive value was 34.1% (CI: 29.5–38.7), and the negative predictive value was 85.6% (CI: 82.2–89.0). Conclusion: The discriminative ability of the LASA fall risk profile was moderate. The predictive validity of the LASA fall risk profile to identify recurrent fallers is limited among older persons who consulted the emergency department or general practitioner after a fall. [ABSTRACT FROM AUTHOR]

Studies of vitamin D and calcium for fracture prevention have produced inconsistent results, as a result of different vitamin D status and calcium intake at baseline, different doses and poor to adequate compliance. This study tries to define the types of patients, both at risk of osteoporosis and with established disease, who may benefit from calcium and vitamin D supplementation. The importance of adequate compliance in these individuals is also discussed. Calcium and vitamin D therapy has been recommended for older persons, either frail and institutionalized or independent, with key risk factors including decreased bone mineral density (BMD), osteoporotic fractures, increased bone remodelling as a result of secondary hyperparathyroidism and increased propensity to falls. In addition, treatment of osteoporosis with a bisphosphonate was less effective in patients with vitamin D deficiency. Calcium and vitamin D supplementation is a key component of prevention and treatment of osteoporosis unless calcium intake and vitamin D status are optimal. For primary disease prevention, supplementation should be targeted to those with dietary insufficiencies. Several serum 25-hydroxyvitamin D (25(OH)D) cut-offs have been proposed to define vitamin D insufficiency (as opposed to adequate vitamin D status), ranging from 30 to 100 nmol/l. Based on the relationship between serum 25(OH)D, BMD, bone turnover, lower extremity function and falls, we suggest that 50 nmol/l is the appropriate serum 25(OH)D threshold to define vitamin D insufficiency. Supplementation should therefore generally aim to increase 25(OH)D levels within the 50–75 nmol/l range. This level can be achieved with a dose of 800 IU/day vitamin D, the dose that was used in succesfull fracture prevention studies to date; a randomized clinical trial assessing whether higher vitamin D doses achieve a greater reduction of fracture incidence would be of considerable interest. As calcium balance is not only affected by vitamin D status but also by calcium intake, recommendations for adequate calcium intake should also be met. The findings of community-based clinical trials with vitamin D and calcium supplementation in which compliance was moderate or less have often been negative, whereas studies in institutionalized patients in whom medication administration was supervised ensuring adequate compliance demonstrated significant benefits. [ABSTRACT FROM AUTHOR]

Background. This study explored the associations between various types of activities, their underlying physical components, and recurrent falling in community-dwelling older persons. Methods. This study included 1,329 community-dwelling persons (≥65 years) of the Longitudinal Aging Study Amsterdam (LASA). The time spent in walking, cycling, light and heavy household activities, and two sports was measured using the LASA Physical Activity Questionnaire (LAPAQ). Physical activity components included strength, intensity, mechanical strain, and turning. Time to second fall in a 6-month period was measured during 3 years with fall calendars. Cox proportional hazards models were adjusted for confounders and stratified for physical performance and sex in case of significant (p < .10) interaction. Results. During 3 years, 325 (24.5%) persons became recurrent fallers. In women, doing light (hazard ratios [HRs] = 0.40, 95% confidence intervals [CIs] = 0.20–0.79) or heavy household activities (HR = 0.63, CI = 0.44–0.79) was associated with a decreased risk of recurrent falling. In persons with good physical performance, doing sports (HR = 1.56, CI = 1.07–2.28), high intensity (HR > 1.75, CI = 1.09–3.16), and high mechanical strain (HR = 1.70, CI = 1.01–2.83) activities was associated with an increased risk of recurrent falling. Conclusions. The results suggest that the relationship between physical activity and recurrent falling differs per type of activity and is modified by physical performance. Doing household activities was associated with a decreased risk of recurrent falling in women. In physically fit older persons, doing sports or activities with high intensity or mechanical strain demands was associated with an increased risk of recurrent falling. [ABSTRACT FROM PUBLISHER]

Background: Dementia with Lewy bodies (DLB) is a complex, progressive neurodegenerative disease with considerable phenotypic, pathological, and genetic heterogeneity.Objective: We tested if genetic variants in part explain the heterogeneity in DLB.Methods: We tested the effects of variants previously associated with DLB (near APOE, GBA, and SNCA) and polygenic risk scores for Alzheimer's disease (AD-PRS) and Parkinson's disease (PD-PRS). We studied 190 probable DLB patients from the Alzheimer's dementia cohort and compared them to 2,552 control subjects. The p-tau/Aβ1-42 ratio in cerebrospinal fluid was used as in vivo proxy to separate DLB cases into DLB with concomitant AD pathology (DLB-AD) or DLB without AD (DLB-pure). We studied the clinical measures age, Mini-Mental State Examination (MMSE), and the presence of core symptoms at diagnosis and disease duration.Results: We found that all studied genetic factors significantly associated with DLB risk (all-DLB). Second, we stratified the DLB patients by the presence of concomitant AD pathology and found that APOE ɛ4 and the AD-PRS associated specifically with DLB-AD, but less with DLB-pure. In addition, the GBA p.E365K variant showed strong associated with DLB-pure and less with DLB-AD. Last, we studied the clinical measures and found that APOE ɛ4 associated with reduced MMSE, higher odds to have fluctuations and a shorter disease duration. In addition, the GBA p.E365K variant reduced the age at onset by 5.7 years, but the other variants and the PRS did not associate with clinical features.Conclusion: These finding increase our understanding of the pathological and clinical heterogeneity in DLB. [ABSTRACT FROM AUTHOR]

Long-term gender-affirming hormone therapy (GHT) in older transgender individuals could have beneficial effects on cognitive functioning. Cardiovascular risk factors and psychological factors are known determinants of cognition. Despite the rising number of older transgender individuals, only few studies have examined cognitive functioning in this population. We aimed to assess differences in cognitive functioning between transgender women, and non-transgender (cisgender) women and men, and investigated the contribution of cardiovascular risk factors and psychological factors on these differences. In this study, 37 transgender women (age range 55 to 69) receiving GHT for at least ten years (range 10.2 to 41.6) were examined, and their cognitive functioning was compared to an age and education level matched cohort consisting of 222 cisgender women and men from the Longitudinal Aging Study Amsterdam. Linear regression analyses were performed. Cognitive functioning was assessed by neuropsychological tests including Mini-Mental State Examination (MMSE), Category Fluency animals, Letter Fluency D, 15-Word test (15WT) immediate and delayed recall. Additionally, cardiovascular risk factors and psychological factors such as cardiovascular disease, hypertension, antihypertensive use, statin use, diabetes mellitus, overweight, smoking, alcohol consumption, psychopharmaceutical use, anxiety and depression symptoms were collected. Transgender women had higher MMSE scores compared with cisgender women (+0.9, 95% CI 0.4 to 1.5), and cisgender men (+1.1, 95% CI 0.4 to 1.8). On all other tests transgender women performed similar to cisgender men. Transgender women performed at a lower level than cisgender women on 15WT immediate recall, -5.5, 95% CI -7.6 to -3.4, and 15WT delayed recall, -2.7, 95% CI -3.7 to -1.7, and equal to cisgender women on Fluency animals and Fluency D. Cardiovascular and psychological factors (i.e., cardiovascular disease and depression symptoms) partly explained differences on MMSE score between transgender women and cisgender-control groups. The results of this study do not indicate a need for tailored hormone treatment strategies for older transgender women, based on cognitive aspects after long-term GHT. As one of the first studies, this study compared older transgender women to a large cohort of cisgender men and women regarding cognitive functioning and took into account numerous potential influencing factors. Limitations include difference in test procedures and the cross-sectional design of the study. Cognitive differences between transgender women and cisgender women and men were small, albeit significant. This may suggest that long-term GHT effects on cognitive functioning in older transgender women are minimal. van Heesewijk JO, Dreijerink KMA, Wiepjes CM, et al. Long-Term Gender-Affirming Hormone Therapy and Cognitive Functioning in Older Transgender Women Compared With Cisgender Women and Men. J Sex Med 2021;18:1434–1443. [ABSTRACT FROM AUTHOR]

Studying the genome of centenarians may give insights into the molecular mechanisms underlying extreme human longevity and the escape of age-related diseases. Here, we set out to construct polygenic risk scores (PRSs) for longevity and to investigate the functions of longevityassociated variants. Using a cohort of centenarians with maintained cognitive health (N = 343), a population-matched cohort of older adults from 5 cohorts (N = 2905), and summary statistics data from genome-wide association studies on parental longevity, we constructed a PRS including 330 variants that significantly discriminated between centenarians and older adults. This PRS was also associated with longer survival in an independent sample of younger individuals (p = .02), leading up to a 4-year difference in survival based on common genetic factors only. We show that this PRS was, in part, able to compensate for the deleterious effect of the APOE-ε4 allele. Using an integrative framework, we annotated the 330 variants included in this PRS by the genes they associate with. We find that they are enriched with genes associated with cellular differentiation, developmental processes, and cellular response to stress. Together, our results indicate that an extended human life span is, in part, the result of a constellation of variants each exerting small advantageous effects on aging-related biological mechanisms that maintain overall health and decrease the risk of age-related diseases. [ABSTRACT FROM AUTHOR]

Background: Age-related cognitive decline has large-scale functional and economic consequences and understanding its' pathophysiological mechanisms is therefore essential. Previous research has suggested associations between hormones adiponectin, ghrelin and leptin and neurodegenerative disease. However, their association with age-related cognitive decline has not been fully described. We examine the association between serum high-molecular-weight (HMW) adiponectin, ghrelin and leptin and age-related cognitive decline in older adults.Methods: The associations between HMW adiponectin, ghrelin and leptin and the Mini-Mental-State-Examination, Coding task (Coding), 15 Words Test (15WT) and composite Z-score (general cognitive function) were analyzed by means of a sex-stratified multivariable linear regression analysis in a population-based cohort of 898 older adults at baseline and after 3 years of follow-up.Results: In women, we found a positive association between HMW adiponectin and general cognitive function at baseline (fully adjusted model composite Z-score standardized regression co-efficient beta [β] = .089, p = .025). After 3 years of follow-up, HMW adiponectin was associated with more decline in general cognitive function and information processing speed (fully adjusted model composite Z-score β = -.123, p = .018; Coding β = -.116, p = .027). Ghrelin and leptin were significantly associated with memory in a baseline subgroup analysis of older women. For men, we found no significant associations at baseline or follow-up.Conclusion: Our results show variable associations between hormones HMW adiponectin, ghrelin and leptin and age-related cognitive decline in women but not in men. As there was no clear trend, all our results should be interpreted with caution. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to examine correlates of discordance between 13-year trajectories of self-reported functional limitations and performance-based physical functioning in older adults. Method: We included 2,135 participants from the population-based Longitudinal Aging Study Amsterdam, the Netherlands, followed across 1995-2008. Self-reported functional limitations included six (instrumental) activities of daily living. Performance-based functioning was a composite of four tests. We used latent class growth analysis and multinomial logistic regression to examine discordance and its correlates. Results: Patterns of discordance and concordance (41% concordance, 46% "overestimation" of daily functioning, 13% "underestimation") appeared to be persistent over 13 years. Older age, male sex, cognitive impairment, absence of pain, and light alcohol use were associated with overestimation. Younger age, female sex, and lower self-rated health were associated with underestimation. Discussion: Factors associated with overestimation partly differ from those associated with underestimation. Factors that are highly stable over time are particularly good indicators of persistent discordance. [ABSTRACT FROM AUTHOR]

Background: Physical performance is an important factor for successful aging. This study aimed to identify distinct trajectories of multiple physical performance measures over 9 years in individuals aged 60-70 years and to evaluate their characteristics and the overlap between measures.Methods: Four physical performance measures were assessed in 440 participants of the Longitudinal Aging Study Amsterdam: tandem stand, gait speed, chair stand, and handgrip strength. Gender-specific latent class models were conducted to obtain distinct trajectories and their degree of overlap.Results: Mean age at baseline was 67.9 (SD 1.7) years for males and 68.0 (SD 1.7) years for females. The optimal number of trajectories differed across measures. For tandem stand, no distinct trajectories were found (all 179 males, 198 females). For gait speed, three trajectories were identified, dependent on baseline speed: high-stable (47 males, 27 females), intermediate-stable (132 males, 130 females), and low-declining performance (6 males, 48 females). Two trajectories were identified for the chair stand: a stable (168 males, 150 females) and declining trajectory (10 males, 38 females). For handgrip strength, three declining trajectories were identified differing in baseline performance: high (55 males, 75 females), intermediate (111 males, 118 females), and low (17 males, 10 females). Overall, 11.9% of males and 5.7% of females were classified in similar trajectories across measures.Conclusions: Trajectories of physical performance were heterogeneous, but showed similar patterns for males and females. Little overlap between measures was shown, suggesting different mechanisms for decline. This study emphasizes the use of multiple domains to assess physical performance. [ABSTRACT FROM AUTHOR]

Background: Previous studies have suggested that the association between APOE ɛ 4 and dementia is moderated by physical activity (PA), but the results remain inconclusive and longitudinal data on cognitive decline are missing. In this study, we examine whether there is a gene-environment interaction between APOE and PA on cognitive decline in older adults using 9-year follow-up data of three cohort studies.Methods: We followed 7,176 participants from three longitudinal cohort studies: Longitudinal Aging Study Amsterdam (LASA), InCHIANTI, and Rotterdam Study for 9 years. PA was assessed with self-reported questionnaires and was categorized in low, moderate, and high PA. Cognitive function was assessed with the Mini-Mental State Examination (MMSE) and cognitive decline was defined as a decrease of three points or more on the MMSE during 3 years follow-up. We fitted logistic regression models using generalized estimating equations adjusting for age, sex, education, depressive symptoms, and number of chronic disease. Interaction between APOE and PA was tested on multiplicative and additive scale.Results: Cohorts were similar in most aspects but InCHIANTI participants were on average older and had lower education. APOE ɛ 4 carriers had higher odds of cognitive decline (odds ratio [OR] = 1.46, 95% confidence interval [CI]: 1.29-1.64) while PA was not significantly associated with cognitive decline overall (moderate PA: OR = 0.87, 0.67-1.13; high PA: OR = 0.71, 0.36-1.40). There was no evidence for an interaction effect between PA and APOE ɛ 4 in cognitive decline in older adults (APOE × moderate PA: p = .83; APOE × high PA: p = .90).Conclusions: Previous claims of a gene-environment interaction between APOE ɛ 4 and PA in cognitive decline are not supported by our results. [ABSTRACT FROM AUTHOR]

Purpose: Higher folate and vitamin-B12 have been linked to lower risk of overweight. However, whether this is a causal effect of these B-vitamins on obesity risk remains unclear and evidence in older individuals is scarce. This study aimed to assess the role of B-vitamin supplementation and levels on body composition in older individuals. Methods: A double-blind, randomized controlled trial in 2919 participants aged ≥ 65 years with elevated homocysteine levels. The intervention comprised a 2-year supplementation with a combination of folic acid (400 µg) and vitamin B12 (500 µg), or with placebo. Serum folate, vitamin-B12, active vitamin-B12 (HoloTC), methylmalonic acid (MMA), and anthropometrics were measured at baseline and after 2 years of follow-up. Dietary intake of folate and vitamin-B12 was measured at baseline in a subsample (n = 603) using a validated food-frequency questionnaire. Fat mass index (FMI) and fat-free mass index (FFMI) were assessed with Dual Energy X-ray absorptiometry (DXA). Results: Cross-sectional analyses showed that a 1 nmol/L higher serum folate was associated with a 0.021 kg/m2 lower BMI (95% CI − 0.039; − 0.004). Higher HoloTC (per pmol/L log-transformed) was associated with a 0.955 kg/m2 higher FMI (95% CI 0.262; 1.647), and higher MMA (per μgmol/L) was associated with a 1.108 kg/m2 lower FMI (95% CI − 1.899; − 0.316). However, random allocation of B-vitamins did not have a significant effect on changes in BMI, FMI or FFMI during 2 years of intervention. Conclusions: Although observational data suggested that folate and vitamin B12 status are associated with body composition, random allocation of a supplement with both B-vitamins combined versus placebo did not confirm an effect on BMI or body composition. [ABSTRACT FROM AUTHOR]

Loop diuretics (LD) may affect bone health by inhibiting renal calcium reuptake. However, whether vitamin D status and dietary calcium intake modify the association between LD and bone outcome is unclear. Therefore, this study aimed to evaluate whether vitamin D level or calcium intake modify the association between LD and various indices of bone health including bone mineral density (BMD) and Trabecular Bone Score (TBS). From The Rotterdam Study, a prospective population-based cohort study, we used data from 6990 participants aged > 45 year with a DXA scan (2002-2008), 6908 participants with femoral neck (FN)-BMD, 6677 participants with lumbar spine (LS)-BMD and 6476 participants with LS-TBS measurements. Use of LD was available from pharmacy dispensing records. Vitamin D (25(OH)D) level was measured in serum, and dietary calcium intake was measured with a validated food frequency questionnaire. Almost eight percent of the participants used LD. The association between LD (past-users compared to never-users) and LS-TBS was significantly different by 25(OH)D concentrations (P for interaction = 0.04). A significantly lower LS-TBS among LD past-users was observed for 25(OH)D ≥ 50 nmol/l compared to ≤ 20 and 20-50 nmol/l (β = - 0.036, 95% CI - 0.060; - 0.013 vs. β = - 0.012, 95% CI - 0.036; 0.013 and β = - 0.031, 95% CI - 0.096; 0.034, respectively). However, no other significant effect modification by 25(OH)D and dietary calcium intake was found in the associations between LD use and bone health outcomes (P-interaction > 0.13). This study suggests that the association between LD use and indices of bone health is not consistently modified by vitamin D or dietary calcium intake. [ABSTRACT FROM AUTHOR]

Background: This study examines the association of both pain severity and within-person pain variability with physical activity (PA) in older adults with osteoarthritis (OA).Methods: Data from the European Project on OSteoArthritis were used. At baseline, clinical classification criteria of the American College of Rheumatology were used to diagnose OA in older adults (65-85 years). At baseline and 12-18 months follow-up, frequency and duration of participation in the activities walking, cycling, gardening, light and heavy household tasks, and sports activities were assessed with the Longitudinal Aging Study Amsterdam Physical Activity Questionnaire. Physical activity was calculated in kcal/day, based on frequency, duration, body weight and the metabolic equivalent of each activity performed. At baseline and 12-18 months follow-up, pain severity was assessed using the pain subscales of the Western Ontario and McMaster Universities OA Index and the Australian/Canadian Hand OA Index. Within-person pain variability was assessed using two-week pain calendars that were completed at baseline, 6 months follow-up and 12-18 months follow-up.Results: Of all 669 participants, 70.0% were women. Sex-stratified multiple linear regression analyses showed that greater pain severity at baseline was cross-sectionally associated with less PA in women (Ratio = 0.95, 95% CI = 0.90-0.99), but not in men (Ratio = 0.99, 95% CI = 0.85-1.15). The longitudinal analyses showed a statistically significant inverse association between pain severity at baseline and PA at follow-up in women (Ratio = 0.94, 95% CI = 0.89-0.99), but not in men (Ratio = 1.00, 95% CI = 0.87-1.11). Greater pain variability over 12-18 months was associated with more PA at follow-up in men (Ratio = 1.18, 95% CI = 1.01-1.38), but not in women (Ratio = 0.94, 95% CI = 0.86-1.03).Conclusions: Greater pain severity and less pain variability are associated with less PA in older adults with OA. These associations are different for men and women. The observed sex differences in the various associations should be studied in more detail and need replication in future research. [ABSTRACT FROM AUTHOR]

The article offers information on the Chronic myeloid leukemia (CML), a chronic myeloproliferative disease, consistently associated with the presence of the Philadelphia chromosome coding for the BCR-ABL oncoprotein. It mentions the use of tyrosine kinase inhibitors (TKIs) in CML has highly improved prognosis of CML patients; and also mentions adequate provision of information is an important determinant of both medication adherence in CML and successful management of side effects.

Background: The Australian/Canadian hand Osteoarthritis Index (AUSCAN) and the Western Ontario and McMaster Universities knee and hip Osteoarthritis Index (WOMAC) are the most commonly used clinical tools to manage and monitor osteoarthritis (OA). Few studies have as yet reported longitudinal changes in the AUSCAN index regarding the hand. While there are published data regarding WOMAC assessments of the hip and the knee, the two sites have always evaluated separately. The current study therefore sought to determine the minimal clinically important difference (MCID) in decline in the AUSCAN hand and WOMAC hip/knee physical function scores over 1 year using anchor-based and distribution-based methods.Methods: The study analysed data collected by the European Project on Osteoarthritis, a prospective observational study investigating six adult cohorts with and without OA by evaluating changes in the AUSCAN and WOMAC physical function scores at baseline and 12-18 months later. Pain and stiffness scores, the performance-based grip strength and walking speed and health-related quality of life measures were used as the study's anchors. Receiver operating characteristic curves and distribution-based methods were used to estimate the MCID in the AUSCAN and WOMAC physical function scores; only the data of those participants who possessed paired (baseline and follow up-measures) AUSCAN and WOMAC scores were included in the analysis.Results: Out of the 1866 participants who were evaluated, 1842 had paired AUSCAN scores and 1845 had paired WOMAC scores. The changes in the AUSCAN physical function score correlated significantly with those in the AUSCAN pain score (r = 0.31). Anchor- and distribution-based approaches converged identifying 4 as the MCID for decline in the AUSCAN hand physical function. Changes in the WOMAC hip/knee physical function score were significantly correlated with changes in both the WOMAC pain score (r = 0.47) and the WOMAC stiffness score (r = 0.35). The different approaches converged identifying two as the MCID for decline in the WOMAC hip/knee physical function.Conclusions: The most reliable MCID estimates of decline over 1 year in the AUSCAN hand and WOMAC hip/knee physical function scores were 4 and 2 points, respectively. [ABSTRACT FROM AUTHOR]

Objective: Previous prospective studies on the association between vitamin D status and depression used a single 25-hydroxyvitamin D (25(OH)D) measurement. We investigated the association between change in serum 25(OH)D and parallel change in depressive symptoms over time in Dutch older adults. Design: A population-based, prospective study in two cohorts of older men and women from the Longitudinal Aging Study Amsterdam. Methods: Serum 25(OH)D concentrations were determined at two time points: in 1995/1996 and 13 years later in the older cohort (aged 65-88y, n = 173) and in 2002/2003 and 6 years later in the younger cohort (55-65 years, n = 450). At these time points, depressive symptoms were measured with the Center for Epidemiologic Studies Depression scale (CES-D). Associations were tested by multiple linear regression analyses. Results: During follow-up, serum 25(OH)D concentrations increased in 32.4% of the older cohort and in 69.8% of the younger cohort. In the older cohort, change in 25(OH)D was not associated with change in CES-D score. In the younger cohort, no associations were observed in participants with higher baseline 25(OH)D concentrations (>58.6 nmol/L), but in those with lower baseline 25(OH)D concentrations, an increase in 25(OH)D was associated with a decrease in CES-D score (adjusted B per 10 nmol/L 25(OH)D increase: -0.62 (95% CI: -1.17, -0.07)). Conclusions: Our study suggests that over 6 years, an increase in serum 25(OH)D is associated with a small decrease in depressive symptoms in young older adults with lower baseline 25(OH)D. Well-designed intervention trials are required to determine causality. [ABSTRACT FROM AUTHOR]

Background: Early identification of people at risk of functional decline is essential for delivering targeted preventive interventions.Objective: The aim of this study is to identify and predict trajectories of functional decline over 9 years in males and females aged 60-70 years.Methods: We included 403 community-dwelling participants from the InCHIANTI study and 395 from the LASA study aged 60-70 years at baseline, of whom the majority reported no functional decline at baseline (median 0, interquartile range 0-1). Participants were included if they reported data on ≥2 measurements of functional ability during a 9-year follow-up. Functional ability was scored with 6 self-reported items on activities of daily living. We performed latent class growth analysis to identify trajectories of functional decline and applied multinomial regression models to develop prediction models of identified trajectories. Analyses were stratified for sex.Results: Three distinct trajectories were identified: no/little decline (219 males, 241 females), intermediate decline (114 males, 158 females), and severe decline (36 males, 30 females). Higher gait speed showed decreased risk of functional limitations in males (intermediate limitations, odds ratio [OR] 0.74, 95% CI 0.57-0.97; severe limitations, OR 0.42, 95% CI 0.26-0.66). The final model in males further included the predictors fear of falling and alcohol intake (no/little decline, area under the receiver operating curve [AUC] 0.68, 95% CI 0.62-0.73; intermediate decline, AUC 0.63, 95% CI 0.56-0.69; severe decline, AUC 0.79, 95% CI 0.71-0.87). In females, higher gait speed showed a decreased risk of intermediate limitations (OR 0.51, 95% CI 0.38-0.68) and severe limitations (OR 0.18, 95% CI 0.07-0.44). Other predictors in females were age, living alone, economic satisfaction, balance, physical activity, BMI, and cardiovascular disease (no/little decline, AUC 0.80, 95% CI 0.75-0.85; intermediate decline, AUC 0.74, 95% CI 0.69-0.79; severe decline, AUC 0.95, 95% CI 0.91-0.99).Conclusion: Already in people aged 60-70 years, 3 distinct trajectories of functional decline were identified in these cohorts over a 9-year follow-up. Predictors of trajectories differed between males and females, except for gait speed. Identification of people at risk is the basis for targeting interventions. [ABSTRACT FROM AUTHOR]

Background: A large number of observational studies have reported harmful effects of low 25-hydroxyvitamin D (25OHD) levels on non-skeletal outcomes. We performed a systematic quantitative review on characteristics of randomized clinical trials (RCTs) included in meta-analyses (MAs) on non-skeletal effects of vitamin D supplementation. Methods and findings: We identified systematic reviews (SR) reporting summary data in terms of MAs of RCTs on selected non-skeletal outcomes. For each outcome, we summarized the results from available SRs and scrutinized included RCTs for a number of predefined characteristics. We identified 54 SRs including data from 210 RCTs. Most MAs as well as the individual RCTs reported null-findings on risk of cardiovascular diseases, type 2 diabetes, weight-loss, and malignant diseases. Beneficial effects of vitamin D supplementation was reported in 1 of 4 MAs on depression, 2 of 9 MAs on blood pressure, 3 of 7 MAs on respiratory tract infections, and 8 of 12 MAs on mortality. Most RCTs have primarily been performed to determine skeletal outcomes, whereas non-skeletal effects have been assessed as secondary outcomes. Only one-third of the RCTs had low level of 25OHD as a criterion for inclusion and a mean baseline 25OHD level below 50 nmol/L was only present in less than half of the analyses. Conclusions: Published RCTs have mostly been performed in populations without low 25OHD levels. The fact that most MAs on results from RCTs did not show a beneficial effect does not disprove the hypothesis suggested by observational findings on adverse health outcomes of low 25OHD levels. [ABSTRACT FROM AUTHOR]

Objective: Low serum 25-hydroxyvitamin D levels (25(OH)D<50nmol/L) are common in older persons and associated with depressive symptoms. Depression and anxiety are highly interrelated, but only very few studies examined the association between 25(OH)D and anxiety. This study investigated whether 25(OH)D levels are related to anxiety symptoms in older persons, both cross-sectionally and over time.Methods: Data from two samples of a large population-based cohort study were used (sample 1: N=1259, 64-88years; sample 2: N=892, 60-98years). Anxiety symptoms were measured with the Hospital Anxiety and Depression Scale - Anxiety subscale at baseline and after three years; serum 25(OH)D was measured at baseline. Cross-sectional and longitudinal relationships between 25(OH)D and anxiety were examined using logistic regression analysis, taking into account relevant confounding variables.Results: Of the participants, 48.0% (sample 1) and 26.4% (sample 2) had 25(OH)D levels <50nmol/L, whereas 8.1% (sample 1) and 6.5% (sample 2) had clinically relevant anxiety symptoms. Cross-sectionally, persons with 25(OH)D<50nmol/L experienced more anxiety symptoms than persons with 25(OH)D≥50nmol/L (sample 1: OR=1.55; 95% CI: 1.03-2.32, p=0.035; sample 2: OR=1.74; 95% CI: 1.03-2.96, p=0.040). However, after adjustment for demographic and lifestyle variables and depressive symptoms, significant associations were no longer observed (p=0.25-0.72). Similarly, 25(OH)D levels were not significantly related to anxiety symptoms after three years in both samples.Conclusions: After adjustment for confounding, there was no cross-sectional or longitudinal association between 25(OH)D levels and anxiety symptoms, independently from depression, in two large samples of older persons. [ABSTRACT FROM AUTHOR]

Objective To examine the role of comorbidity and pain in the associations of hand osteoarthritis (OA) with self-reported and performance-based physical function in a general population of elderly persons. Methods We studied data from 2,942 participants ages 65-85 years in the European Project on OSteoArthritis, a collaborative observational study of 6 European cohorts (from Germany, Italy, The Netherlands, Spain, Sweden, and the UK). Outcome measures included self-reported physical function of the hands measured by the AUStralian/CANadian Osteoarthritis Hand Index (AUSCAN) for hand OA physical function subscale and performance-based grip strength measured using a strain gauge dynamometer. Results Comorbidity was not a confounder in the association of hand OA with self-reported and performance-based functional limitations, while the role of pain as a mediator was confirmed. Anxiety, depression, stroke, and osteoporosis were associated with AUSCAN scores reflecting more impairment. Depression and osteoporosis were associated with less grip strength. Conclusion Although comorbidity was decidedly and independently associated with hand functional limitation, it had no effect on the relationship of hand OA with physical function. Hand OA was found to be associated with both self-reported and performance-based physical function impairment; the association was found to be partially mediated by pain, which reduced its impact. [ABSTRACT FROM AUTHOR]