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BACKGROUND: Overweight and obesity impose a considerable individual and social burden, and the urban environments might encompass factors that contribute to obesity. Nevertheless, there is a scarcity of research that takes into account the simultaneous interaction of multiple environmental factors. OBJECTIVES: Our objective was to perform an exposome-wide association study of body mass index (BMI) in a multicohort setting of 15 studies. METHODS: Studies were affiliated with the Dutch Geoscience and Health Cohort Consortium (GECCO), had different population sizes (688–141,825), and covered the entire Netherlands. Ten studies contained general population samples, others focused on specific populations including people with diabetes or impaired hearing. BMI was calculated from self-reported or measured height and weight. Associations with 69 residential neighborhood environmental factors (air pollution, noise, temperature, neighborhood socioeconomic and demographic factors, food environment, drivability, and walkability) were explored. Random forest (RF) regression addressed potential nonlinear and nonadditive associations. In the absence of formal methods for multimodel inference for RF, a rank aggregation-based meta-analytic strategy was used to summarize the results across the studies. RESULTS: Six exposures were associated with BMI: five indicating neighborhood economic or social environments (average home values, percentage of high-income residents, average income, livability score, share of single residents) and one indicating the physical activity environment (walkability in 5-km buffer area). Living in high-income neighborhoods and neighborhoods with higher livability scores was associated with lower BMI. Nonlinear associations were observed with neighborhood home values in all studies. Lower neighborhood home values were associated with higher BMI scores but only for values up to e300,000. The directions of associations were less consistent for walkability and share of single residents. DISCUSSION: Rank aggregation made it possible to flexibly combine the results from various studies, although between-study heterogeneity could not be estimated quantitatively based on RF models. Neighborhood social, economic, and physical environments had the strongest associations with BMI. [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]

Background: Intrinsic capacity (IC) defined by the WHO refers to the composite of five domains of capacities. So far, developing and validating a standardized overall score of the concept have been challenging partly because its conceptual framework has been unclear. We consider that a person's IC is determined by its domain-specific indicators suggesting a formative measurement model. Aims: To develop an IC score applying a formative approach and assess its validity. Methods: The study sample (n = 1908) consisted of 57–88-year-old participants from the Longitudinal Aging Study Amsterdam (LASA). We used logistic regression models to select the indicators to the IC score with 6-year functional decline as an outcome. An IC score (range 0–100) was constructed for each participant. We examined the known-groups' validity of the IC score by comparing groups based on age and number of chronic diseases. The criterion validity of the IC score was assessed with 6-year functional decline and 10-year mortality as outcomes. Results: The constructed IC score included seven indicators covering all five domains of the construct. The mean IC score was 66.7 (SD 10.3). The scores were higher among younger participants and those who had lower number of chronic diseases. After adjustment for sociodemographic indicators, chronic diseases, and BMI, a one-point higher IC score was associated with a 7% decreased risk for 6-year functional decline and a 2% decreased risk for 10-year mortality. Conclusions: The developed IC score demonstrated discriminative ability according to age and health status and is associated with subsequent functional decline and mortality. [ABSTRACT FROM AUTHOR]

Aims: The aim of the current study was to compare cancellations or postponement of medical care among older adults during the COVID-19 pandemic between 2021 and 2020. Methods: Data of respondents aged ≥ 62 years were used from the longitudinal aging study Amsterdam (LASA), collected in 2020 and 2021, directly after the main COVID-19 waves in the Netherlands. A questionnaire assessed cancellations of medical care and postponed help-seeking behavior. Descriptive analyses were performed. Results: Overall, cancellations declined from 35% in 2020 (sample n = 1128) to 17% in 2021 (sample n = 1020). Healthcare-initiated cancellations declined from 29 to 8%. Respondent-initiated cancellations declined from 12 to 7%. Postponed help-seeking remained around 8%. Conclusions: In 2021, less cancellations were reported compared to just after the first wave of the pandemic in 2020, while postponed help-seeking remained the same. It is important to investigate how cancellations and postponed help-seeking can be prevented in future pandemics. [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]

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]

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]

The Longitudinal Aging Study Amsterdam (LASA) is a prospective cohort study of older adults in the Netherlands, initially based on a nationally representative sample of people aged 55–84 years. The study has been ongoing since 1992, and focuses on the determinants, trajectories and consequences of physical, cognitive, emotional and social functioning. Strengths of the LASA study include its multidisciplinary character, the availability of over 25 years of follow-up, and the cohort-sequential design that allows investigations of longitudinal changes, cohort differences and time trends in functioning. The findings from LASA have been reported in over 600 publications so far (see www.lasa-vu.nl). This article provides an update of the design of the LASA study and its methods, on the basis of recent developments. We describe additional data collections, such as additional nine-monthly measurements in-between the regular three-yearly waves that have been conducted among the oldest old during 2016–2019, and the inclusion of a cohort of older Turkish and Moroccan migrants. [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]

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.Trial Registration: Netherlands Trial Register NTR3845. Registered 6 February 2013. [ABSTRACT FROM AUTHOR]

Background: Elevated plasma homocysteine concentrations are a risk factor for osteoporotic fractures. Lowering homocysteine with combined vitamin B-12 and folic acid supplementation may reduce fracture risk. Objective: This study [B-vitamins for the PRevention Of Osteoporotic Fractures (B-PROOF)] aimed to determine whether vitamin B-12 and folic acid supplementation reduces osteoporotic fracture incidence in hyperhomocysteinemic elderly individuals. Design: This was a double-blind, randomized, placebo-controlled trial in 2919 participants aged ≥65 y with elevated homocysteine concentrations (12-50 µmol/L). Participants were assigned to receive daily 500 µg vitamin B-12 plus 400 μg folic acid or placebo supplementation for 2 y. Both intervention and placebo tablets also contained 600 IU vitamin D3. The primary endpoint was time to first osteoporotic fracture. Exploratory prespecified subgroup analyses were performed in men and women and in individuals younger than and older than age 80 y. Data were analyzed according to intention-to-treat and per-protocol principles. Results: Osteoporotic fractures occurred in 61 persons (4.2%) in the intervention group and 75 persons (5.1%) in the placebo group. Osteoporotic fracture risk was not significantly different between groups in the intention-to-treat analyses (HR: 0.84; 95% CI: 0.58, 1.21) or per-protocol analyses (HR: 0.81; 95% CI: 0.54, 1.21). For persons >80 y, in per-protocol analyses, osteoporotic fracture risk was lower in the intervention group than in the placebo group (HR: 0.27; 95% CI: 0.10, 0.74). The total number of adverse events (including mortality) did not differ between groups. However, 63 and 42 participants in the intervention and placebo groups, respectively, reported incident cancer (HR: 1.56; 95% CI: 1.04, 2.31). Conclusions: These data show that combined vitamin B-12 and folic acid supplementation had no effect on osteoporotic fracture incidence in this elderly population. Exploratory subgroup analyses suggest a beneficial effect on osteoporotic fracture prevention in compliant persons aged >80 y. However, treatment was also associated with increased incidence of cancer, although the study was not designed for assessing cancer outcomes. Therefore, vitamin B-12 plus folic acid supplementation cannot be recommended at present for fracture prevention in elderly people. The B-PROOF study was registered with the Netherlands Trial Register (trialregister.nl) as NTR1333 and at clinicaltrials.gov as NCT00696414. [ABSTRACT FROM AUTHOR]

Background: Low serum 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with insulin resistance, the metabolic syndrome, and type 2 diabetes. Because many non-Western immigrants in the Netherlands are vitamin D deficient, obese, and at high risk of diabetes, vitamin D supplementation may contribute to prevent diabetes and insulin resistance. Objective: We examined the effect of vitamin D supplementation on insulin sensitivity and β cell function in overweight, vitamin D-deficient, non-Western immigrants at high risk of diabetes. Design: The study was a 16-wk, randomized, placebo-controlled trial. A total of 130 non-Western immigrants with prediabetes (fasting glucose concentration >5.5 mmol/L or random glucose concentration from 7.8 to 11.1 mmol/L) and vitamin D deficiency (serum 25[OH]D concentration <50 nmol/L) were randomly assigned after stratification by sex to receive either cholecalciferol (1200 IU/d) or a placebo for 16 wk. All participants received 500 mg Ca/d as calcium carbonate. The primary outcome was the difference in the area under the curve of insulin and glucose after a 75-g oral-glucose-tolerance test after 4 mo of treatment. Secondary outcomes were insulin-sensitivity variables, β cell-function variables, and metabolic syndrome. Results: Mean serum 25(OH)D concentrations increased significantly in the vitamin D compared with placebo groups. After 4 mo of therapy, the mean between-group difference was 38 nmol/L (95% CI: 32.1, 43.9 nmol/L; P < 0.001). There was no significant effect on insulin sensitivity and β cell function. In a post hoc analysis, when patients with diabetes at baseline were excluded, a significant increase in the insulinogenic index was observed in participants who obtained a 25(OH)D concentration ≥60 nmol/L (P = 0.040). Conclusions: Vitamin D supplementation in non-Western vitamin D-deficient immigrants with prediabetes did not improve insulin sensitivity or β cell function or change the incidence of metabolic syndrome. However, after the exclusion of diabetic subjects, an improvement in the insulinogenic index was observed in participants who obtained a 25(OH)D concentration ≥60 nmol/L. [ABSTRACT FROM AUTHOR]

Background: Vitamin D Status is currently diagnosed by measuring serum 25-hydroxyvitamin D [25(OH)D]. Objective: This study aimed to develop a risk profile that can be used to easily identify older individuals at high risk of vitamin D deficiency. Design: This study was performed within the Longitudinal Aging Study Amsterdam, an ongoing cohort study in a representative sample of the Dutch older population (n = 1509 for the development sample and n = 1100 for the Validation sample). Prediction models for serum 25(OH)D concentrations <50 and <30 nmol/L were developed by using backward logistic regression. Risk scores were calculated by dividing the individual regression coefficients by the regression coefficient with the lowest β to create simple scores. Results: Serum 25(OH)D concentrations <50 and <30 nmol/L were present in 46.2% and 17.5% of participants, respectively. The model for the prediction of concentrations <50 nmol/L consisted of 13 easily assessable predictors, whereas the model for concentrations <30 nmol/L contained 10 predictors. The resulting areas under the curve (AUCs) were 0.78 and 0.80, respectively. The AUC in the ex-ternal Validation data set was 0.71 for the <50-nmol/L model. At a cutoff of 58 in total risk score (range: 8-97), the model predicted concentrations <50 nmol/L with a sensitivity of 61% and a specificity of 82%, whereas these values were 61% and 84%, respectively, at a cutoff of 110 in the total risk score (range: 6-204) in the model for concentrations <30 nmol/L. Conclusions: Two total risk scores, including 13 or 10 predictors that can easily be assessed, were developed and are able to predict serum 25(OH)D concentrations <50 and <30 nmol/L accurately. These risk scores may be useful in clinical practice to identify persons at risk of vitamin D deficiency. [ABSTRACT FROM AUTHOR]

Summary Background Recent evidence indicates that a lower plasma level of 25-hydroxyvitamin D (25 OHD) is associated with a higher risk of the metabolic syndrome. It has not been studied in older people with a high prevalence of vitamin D insufficiency. Objective This study investigates the association between vitamin D status and the metabolic syndrome in community-dwelling older persons in the Netherlands. Design and patients The study is part of the Longitudinal Aging Study Amsterdam, an ongoing cohort study in a representative sample of Dutch older persons. A total of 1286 subjects (629 men and 657 women) between the ages of 65 and 88 years participated in the study. Measurements Metabolic syndrome (U.S. National Cholesterol Education Program definition) and its individual components were assessed as well as serum 25 OHD levels. Results Among the participants, the prevalence of the metabolic syndrome was 37·0%. The mean 25 OHD level was 53·3 n m; 47·8% had 25 OHD levels below 50 n m. There was a significantly increased risk of the metabolic syndrome in the subjects with serum 25 OHD levels below 50 n m, compared with that of subjects with levels over 50 n m [odds ratio (OR) = 1·54; 95% confidence interval (CI) 1·23-1·94]. After adjustment for confounders, age, sex, season, years of education, alcohol use, total activity, smoking and PTH, the OR was 1·29 (95% CI 1·00-1·68). The association between vitamin D deficiency and the metabolic syndrome was mainly determined by the components low HDL and (high) waist circumference. Conclusions Vitamin D deficiency is common in the older population in the Netherlands, and subjects with serum 25 OHD below 50 n m have a higher risk of the metabolic syndrome. [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]

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]

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]

Observational studies suggest that low concentrations of serum 25-hydroxyvitamin D (25(OH)D) and high concentrations of parathyroid hormone (PTH) are associated with a higher risk of mortality. The aim of this study was to examine whether 25(OH)D and PTH concentrations are independently associated with overall and disease-specific (cardiovascular and cancer-related) mortality in a large, prospective population-based cohort of older adults. Data from 1317 men and women (65–85 years) of the Longitudinal Aging Study Amsterdam were used. Cox proportional hazard analyses were used to examine whether 25(OH)D and PTH at baseline were associated with overall mortality (with a follow-up of 18 years) and disease-specific mortality (with a follow-up of 13 years). Compared to persons in the reference category of ≥75 nmol/L, persons with serum 25(OH)D <25 nmol/L (HR 1.46; 95% CI: 1.12–1.91) and 25–49.9 nmol/L (HR 1.24; 95% CI: 1.01–1.53) had a significantly higher risk of overall mortality, as well as men with baseline PTH concentrations ≥7 pmol/L (HR 2.54 (95% CI: 1.58–4.08)), compared to the reference category of <2.33 pmol/L. The relationship of 25(OH)D with overall mortality was partly mediated by PTH. Furthermore, men with PTH concentrations of ≥7 pmol/L (HR 3.22; 95% CI: 1.40–7.42) had a higher risk of cardiovascular mortality, compared to the reference category. No significant associations of 25(OH)D or PTH with cancer-related mortality were observed. Both 25(OH)D and PTH should be considered as important health markers. [ABSTRACT FROM AUTHOR]

Objectives First, the association between serum 25-hydroxyvitamin D (25[OH]D) and cognitive performance was examined. Second, we assessed whether there was evidence for an interplay between 25(OH)D and glucose homeostasis in the association with cognitive performance. Design, Setting, and Participants Associations were studied using cross-sectional data of 776 (3 domains) up to 2722 (1 domain) Dutch community-dwelling older adults, aged 65 years or older. Measurements Serum 25(OH)D, plasma glucose, and insulin concentrations were obtained. Cognitive performance was assessed with an extensive cognitive test battery. Prevalence ratios (PRs) were calculated to quantify the association between 25(OH)D and cognition; poor performance was defined as the worst 10% of the distribution of the cognitive scores. Results The overall median MMSE score was 29 (IQR 28–30). Higher serum 25(OH)D was associated with better attention and working memory, PR 0.50 (95% CI 0.29–0.84) for the third serum 25(OH)D tertile, indicating a 50% lower probability of being a poor performer than participants in the lowest tertile. Beneficial trends were shown for 25(OH)D with executive function and episodic memory. Serum 25(OH)D was not associated with plasma glucose or insulin. Plasma insulin only modified the association between serum 25(OH)D and executive function ( P for interaction: .001), suggesting that the improvement in executive function with high 25(OH)D concentrations is stronger in participants with high plasma insulin concentrations compared with those with low plasma insulin concentrations. Conclusion Higher 25(OH)D concentrations significantly associated with better attention and working memory performance. This study does not demonstrate an interplay between serum 25(OH)D and glucose homeostasis in the association with cognitive performance. [ABSTRACT FROM AUTHOR]

Objective To investigate whether the CYP2C9*2 and *3 variants modify benzodiazepine-related fall risk. Design Three prospective studies; the Rotterdam Study, B-PROOF, and LASA. Setting Community-dwelling individuals living in or near five Dutch cities. Participants There were 11,485 participants aged ≥55 years. Measurements Fall incidents were recorded prospectively. Benzodiazepine use was determined using pharmacy dispensing records or interviews. Cox proportional hazard models adjusted for age and sex were applied to determine the association between benzodiazepine use and fall risk stratified for CYP2C9 genotype and comparing benzodiazepine users to nonusers. The results of the three studies were combined applying meta-analysis. Within benzodiazepine users, the association between genotypes and fall risk was also assessed. Results Three thousand seven hundred five participants (32%) encountered a fall during 91,996 follow-up years, and 4% to 15% (depending on the study population) used benzodiazepines. CYP2C9 variants had frequencies of 13% for the *2 allele and 6% for the *3 allele. Compared to nonusers, current benzodiazepine use was associated with an 18% to 36% increased fall risk across studies with a combined hazard ratio (HR) = 1.26 (95% confidence interval [CI], 1.13; 1.40). CYP2C9*2 or *3 allele variants modified benzodiazepine-related fall risk. Compared to nonusers, those carrying a CYP2C9*2 or *3 allele and using benzodiazepines had a 45% increased fall risk (HR, 1.45 95% CI, 1.21; 1.73), whereas CYP2C9*1 homozygotes using benzodiazepines had no increased fall risk (HR, 1.14; 95% CI, 0.90; 1.45). Within benzodiazepine users, having a CYP2C9*2 or *3 allele was associated with an increased fall risk (HR, 1.35; 95% CI, 1.06; 1.72). Additionally, we observed an allele dose effect; heterozygous allele carriers had a fall risk of (HR = 1.30; 95% CI, 1.05; 1.61), and homozygous allele carriers of (HR = 1.91 95% CI, 1.23; 2.96). Conclusions CYP2C9*2 and *3 allele variants modify benzodiazepine-related fall risk. Those using benzodiazepines and having reduced CYP2C9 enzyme activity based on their genotype are at increased fall risk. In clinical practice, genotyping might be considered for elderly patients with an indication for benzodiazepine use. However, because the exact role of CYP2C9 in benzodiazepine metabolism is still unclear, additional research is warranted. [ABSTRACT FROM AUTHOR]

Background: Evidence on the association between single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) and depressive symptoms is inconclusive., Objectives: The primary aim of the study was to investigate the association between SNPs in the VDR gene and depressive symptoms., Methods: In a sample of older adults from the Longitudinal Ageing Study Amsterdam (n = 922), depressive symptoms were assessed using the Centre for Epidemiological Studies Depression scale (CES-D scale) at baseline and after 3, 6, and 10 y of follow-up. Blood samples for SNP and serum 25-hydroxyvitamin D 3 (25(OH)D 3 ) determination were obtained at baseline. The association between 13 SNPs in the VDR gene and the course of depressive symptoms were evaluated using linear mixed models. The interaction between SNPs and serum 25(OH)D3 in relation to depressive symptoms was evaluated using multiple linear regression., Results: No SNPs were associated with the course of depressive symptoms. Significant interactions between serum 25(OH)D3 and SNPs in the VDR gene were found. Stratified analysis revealed that within the GG genotype strata, 10 nmol/L higher serum 25(OH)D 3 was associated with 0.27 (95% CI: -0.50, -0.04) and 0.23 (95% CI: -0.48, 0.02) lower scores on the CES-D scale for Cdx-2 and 1b-G-886A, respectively. This association was not found in persons having the GA or AA genotype., Conclusions: No SNPs are associated with the course of depressive symptoms. Stratified analysis shows that the effect of serum 25(OH)D 3  concentrations on depressive symptoms is different among genotypes of Cdx-2 and 1b-G-886A. Future research should elucidate on the function of Cdx-2 and 1b-G-886A to describe their effect., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2021. Published by Elsevier B.V.)

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Objectives: The objectives of this study were to investigate the effect of genetic and social factors on depressive symptoms and depression over time and to test whether social factors moderate the relationship between depressive symptoms and its underlying genetics in later life., Methods: The study included 2,279 participants with a mean follow-up of 15 years from the Longitudinal Aging Study Amsterdam with genotyping data. The personal genetic loading for depression was estimated for each participant by calculating a polygenic risk scores (PRS-D), based on 23,032 single nucleotide polymorphisms associated with major depression in a large genome-wide association study. Partner status, network size, received and given emotional support were assessed via questionnaires and depressive symptoms were assessed using the CES-D Scale. A CES-D Scale of 16 and higher was considered as clinically relevant depression., Results: Higher PRS-D was associated with more depressive symptoms whereas having a partner and having a larger network size were independently associated with less depressive symptoms. After extra adjustment for education, cognitive function and functional limitations, giving more emotional support was also associated with less depressive symptoms. No evidence for gene-environment interaction between PRS-D and social factors was found. Similar results were found for clinically relevant depression., Conclusion: Genetic and social factors are independently associated with depressive symptoms over time in older adults. Strategies that boost social functioning should be encouraged in the general population of older adults regardless of the genetic liability for depression., (Copyright © 2020 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

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/m 2 lower BMI (95% CI - 0.039; - 0.004). Higher HoloTC (per pmol/L log-transformed) was associated with a 0.955 kg/m 2 higher FMI (95% CI 0.262; 1.647), and higher MMA (per μgmol/L) was associated with a 1.108 kg/m 2 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.

Background: Monitoring of trends in functioning of older adults provides indispensable information for health care policy. This study examined trends in multiple indicators of functioning among Dutch older adults across a period of 20 years., Methods: Data from the Longitudinal Aging Study Amsterdam were used. We included 10 870 observations of 3803 respondents aged 64-84 years across seven waves (1992-12) and 931 observations of 603 respondents aged 85-94 years across four waves (2001-12). At each wave, 8 indicators of functioning were measured: multimorbidity, severe functional limitations, depression, anxiety, cognitive impairment, physical inactivity, loneliness and social isolation. In addition, a sum score (range: 0-8) of these indicators was calculated, with a score of ≥5 indicating 'multiple problems.' Trends in functioning over time were assessed using Generalized Estimating Equation analyses., Results: In the 64-84-years-olds, the prevalence of multimorbidity increased over time [OR(year) = 1.06, 95% CI = 1.05-1.06], whereas the prevalence of the other indicators decreased [i.e. cognitive impairment, physical inactivity (in women) and loneliness (in women)] or remained stable [i.e. severe functional limitations, depression, anxiety, physical inactivity (in men), loneliness (in men) and social isolation]. In the 85-94-year-olds, the prevalence of severe functional limitations increased over time [OR(year) = 1.08, 95% CI = 1.02-1.13], whereas the prevalence of the other indicators remained stable. In both age groups, the prevalence of 'multiple problems' remained stable., Conclusion: Unfavorable trends were observed in multimorbidity among 64-84-years-olds and in severe functional limitations among 85-94-year-olds. Favorable trends were found in cognitive impairment, physical inactivity (in women) and loneliness (in women) among 64-84-years-olds., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Public Health Association.)

Background: Identifying those people at increased risk of early functional decline in activities of daily living (ADL) is essential for initiating preventive interventions. The aim of this study is to develop and validate a clinical prediction model for onset of functional decline in ADL in three years of follow-up in older people of 65-75 years old., Methods: Four population-based cohort studies were pooled for the analysis: ActiFE-ULM (Germany), ELSA (United Kingdom), InCHIANTI (Italy), LASA (Netherlands). Included participants were 65-75 years old at baseline and reported no limitations in functional ability in ADL at baseline. Functional decline was assessed with two items on basic ADL and three items on instrumental ADL. Participants who reported at least some limitations at three-year follow-up on any of the five items were classified as experiencing functional decline. Multiple logistic regression analysis was used to develop a prediction model, with subsequent bootstrapping for optimism-correction. We applied internal-external cross-validation by alternating the data from the four cohort studies to assess the discrimination and calibration across the cohorts., Results: Two thousand five hundred sixty community-dwelling people were included in the analyses (mean age 69.7 ± 3.0 years old, 47.4% female) of whom 572 (22.3%) reported functional decline at three-year follow-up. The final prediction model included 10 out of 22 predictors: age, handgrip strength, gait speed, five-repeated chair stands time (non-linear association), body mass index, cardiovascular disease, diabetes, chronic obstructive pulmonary disease, arthritis, and depressive symptoms. The optimism-corrected model showed good discrimination with a C statistic of 0.72. The calibration intercept was 0.06 and the calibration slope was 1.05. Internal-external cross-validation showed consistent performance of the model across the four cohorts., Conclusions: Based on pooled cohort data analyses we were able to show that the onset of functional decline in ADL in three years in older people aged 65-75 years can be predicted by specific physical performance measures, age, body mass index, presence of depressive symptoms, and chronic conditions. The prediction model showed good discrimination and calibration, which remained stable across the four cohorts, supporting external validity of our findings.

Background: Decreased physical function is known to raise mortality risk. Little is known about how different physical function measures compare in predicting mortality risk in older men and women. The objective of this study was to compare four, objective and self-reported, physical function measures in predicting 15-year mortality risk in older men and women., Methods: Data were used from the Longitudinal Aging Study Amsterdam (LASA), an ongoing cohort study in a population-based sample of the older Dutch population, sampled from municipal records. The 1995-96 cycle, including 727 men and 778 women aged 65-88 years, was considered as the baseline. Mortality was followed up through September 1, 2011. Physical function measures were: lower-body performance (chair stands test, walk test and tandem stand); handgrip strength (grip strength dynamometer); lung function (peak expiratory flow rate); functional limitations (self-report of difficulties in performing six activities of daily living). Cox proportional hazard models were used to determine the predictive value of each physical function measure for 15-year mortality risk, adjusted for demographic, lifestyle and health variables as potential confounders., Results: 1031 participants (68.5%) had died. After adjustments for confounders, in models assessing single functional measures, peak flow was the strongest predictor of all-cause mortality in men (HR 1.76, CI 1.38-2.26, CI) and lower-body performance in women (HR 1.97,CI 1.40-2.76, CI). In a model including all four functional measures only peak flow was statistically significant in predicting mortality in both genders (men HR 1.54,CI 1.18-2.01 and women HR 1.45,CI 1.08-1.94). In women, lower-body performance (HR 1.66, CI 1.15-2.41) followed by grip strength (HR 1.38, CI 1.02-1.89), and in men, functional limitations (HR 1.43, CI 1.14-1.8) were the other significant predictors of all-cause mortality., Conclusion: Both objective and self-reported measures of physical functioning predicted all-cause mortality in a representative sample of the older Dutch population to different extents in men and women. Peak flow contributed important unique predictive value for mortality in both men and women. In women, however, lower-body performance tests had better predictive ability. A second-best predictor in men was self-reported functional limitations. Peak flow, and possibly one of the other measures, may be used in clinical practice for assessment in the context of time constraints.

Background: Folic acid and vitamin B12 play key roles in one-carbon metabolism. Disruption of one-carbon metabolism may be involved in the risk of cancer. Our aim was to assess the long-term effect of supplementation with both folic acid and vitamin B12 on the incidence of overall cancer and on colorectal cancer in the B Vitamins for the Prevention of Osteoporotic Fractures (B-PROOF) trial., Methods: Long-term follow-up of B-PROOF trial participants ( N = 2,524), a multicenter, double-blind randomized placebo-controlled trial designed to assess the effect of 2 to 3 years daily supplementation with folic acid (400 μg) and vitamin B12 (500 μg) versus placebo on fracture incidence. Information on cancer incidence was obtained from the Netherlands cancer registry (Integraal Kankercentrum Nederland), using the International Statistical Classification of Disease (ICD-10) codes C00-C97 for all cancers (except C44 for skin cancer), and C18-C20 for colorectal cancer., Results: Allocation to B vitamins was associated with a higher risk of overall cancer [171 (13.6%) vs. 143 (11.3%); HR 1.25; 95% confidence interval (CI), 1.00-1.53, P = 0.05]. B vitamins were significantly associated with a higher risk of colorectal cancer [43(3.4%) vs. 25(2.0%); HR 1.77; 95% CI, 1.08-2.90, P = 0.02]., Conclusions: Folic acid and vitamin B12 supplementation was associated with an increased risk of colorectal cancer., Impact: Our findings suggest that folic acid and vitamin B12 supplementation may increase the risk of colorectal cancer. Further confirmation in larger studies and in meta-analyses combining both folic acid and vitamin B12 are needed to evaluate whether folic acid and vitamin B12 supplementation should be limited to patients with a known indication, such as a proven deficiency., (©2018 American Association for Cancer Research.)

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.

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., Competing Interests: Ageing (TILDA) is funded by the Irish Government and the Atlantic Philanthropies, along with support from Irish Life PLC in the form of a charitable gift. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: The current diagnosis-oriented approach of dizziness does not suit older patients. Often, it is difficult to identify a single underlying cause, and when a diagnosis is made, therapeutic options may be limited. Identification of predictors of dizziness may provide new leads for the management of dizziness in older patients. The aim of the present study was to investigate long-term predictors of regular dizziness in older persons., Methods: Population-based cohort study of 1,379 community-dwelling participants, aged ≥60 years, from the Longitudinal Aging Study Amsterdam (LASA). Regular dizziness was ascertained during face-to-face medical interviews during 7- and 10-year follow-up. We investigated 26 predictors at baseline from six domains: socio-demographic, medical history, medication, psychological, sensory, and balance/gait. We performed multivariate logistic regression analyses with presence of regular dizziness at 7- and 10-year follow-up as dependent variables. We assessed the performance of the models by calculating calibration and discrimination., Results: Predictors of regular dizziness at 7-year follow-up were living alone, history of dizziness, history of osteo/rheumatoid arthritis, use of nitrates, presence of anxiety or depression, impaired vision, and impaired function of lower extremities. Predictors of regular dizziness at 10-year follow-up were history of dizziness and impaired function of lower extremities. Both models showed good calibration (Hosmer-Lemeshow P value of 0.36 and 0.31, respectively) and acceptable discrimination (adjusted AUC after bootstrapping of 0.77 and 0.71)., Conclusions: Dizziness in older age was predicted by multiple factors. A multifactorial approach, targeting potentially modifiable predictors (e.g., physical exercise for impaired function of lower extremities), may add to the current diagnosis-oriented approach.

Background: Medication use is a potentially modifiable risk factor for falling; psychotropic and cardiovascular drugs have been indicated as main drug groups that increase fall risk. However, evidence is mainly based on studies that recorded falls retrospectively and/or did not determine medication use at the time of the fall. Therefore, we investigated the associations indicated in the literature between medication use and falls, using prospectively recorded falls and medication use determined at the time of the fall., Methods: Data from the B-PROOF (B-vitamins for the prevention of osteoporotic fractures) study were used, concerning community-dwelling elderly aged ≥65 years. We included 2,407 participants with pharmacy dispensing records. During the 2- to 3-year follow-up, participants recorded falls using a fall calendar. Cox proportional hazard models were applied, adjusting for potential confounders including age, sex, health status variables and concomitant medication use., Results: During follow-up, 1,147 participants experienced at least one fall. Users of anti-arrhythmic medication had an increased fall risk (hazard ratio [HR] 1.61; 95% confidence interval [CI] 1.12-2.32) compared with non-users. Similarly, non-selective beta-blocker use was associated with an increased fall risk (HR 1.41 [95% CI 1.12-1.78]), while statin use was associated with a lower risk (HR 0.81 [95% CI 0.71-0.94]). Benzodiazepine use (HR 1.32 [95% CI 1.02-1.71]), and antidepressant use (HR 1.40 [95% CI 1.07-1.82]) were associated with an increased fall risk. Use of other cardiovascular and psychotropic medication was not associated with fall risk., Conclusion: Our results strengthen the evidence for an increased fall risk in community-dwelling elderly during the use of anti-arrhythmics, non-selective beta-blockers, benzodiazepines, and antidepressant medication. Clinicians should prescribe these drugs cautiously and if possible choose safer alternatives for older patients.

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 between OC and CVD: hazard ratio (HR) was 0.97 (95% CI 0.90-1.04) per nmol/l higher plasma OC, adjusted for age and sex. There was a statistical interaction between plasma OC, age, and sex on CVD (P=0.014). In those subjects aged ≥75 years, age-adjusted HRs (95% CI) were 0.86 (0.75-0.99) in men and 1.16 (1.03-1.31) in women per nmol/l higher plasma OC. 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., (© 2014 European Society of Endocrinology.)

Background: Elevated homocysteine levels are a risk indicator for cardiovascular disease, fractures and cognitive decline. Previous studies indicated associations between homocysteine levels and medication use, including antihypertensive, lipid-lowering and antidiabetic medication. However, results were often contradictory and inconclusive. Our objective was to study the associations established previously in more detail by sub-classifying medication groups, and investigate the potential mediating role of vitamin B12 and folate status., Materials and Methods: Baseline data from the B-PROOF (B-vitamins for the PRevention Of Osteoporotic Fractures) study were used. We included 2,912 participants aged ≥65 years, with homocysteine levels of 12-50 μmol/L and creatinine levels ≤150 μmol/L, for whom self-reported medication data were available. We used multivariable linear regression models and analysis of covariance to assess the association between medication use and plasma homocysteine levels, and the potential mediation by serum vitamin B12 and folate., Results: The mean age was 74 years (standard deviation, 6.5), 50 % were women, and median homocysteine levels were 14 µmol/L [interquartile range, 13-17 µmol/L]. Higher mean homocysteine levels were observed in users vs. non-users for diuretics (15.2 vs. 14.9, p = 0.043), high-ceiling sulphonamide diuretics (16.0 vs. 14.9, p < 0.001), medication acting via the renin-angiotensin system (15.2 vs. 14.9, p = 0.029) and metformin (15.6 vs. 15.1, p = 0.006). Non-selective β-blocker use was associated with lower mean homocysteine levels (14.4 vs. 15.0, p = 0.019). Only this association was mediated by an underlying association with vitamin B12 and folate levels., Conclusion: The associations between homocysteine levels and medication use appear to be fairly modest. Our results suggest that medication use is unlikely to contribute to clinically relevant changes in plasma homocysteine levels.

Unlabelled: The aim of this study was to determine the prevalence of 25-hydroxyvitamin D (25(OH)D) deficiency in a hospital-based population of both native Dutch and non-Western immigrants and to investigate the influence of immigrant status on the prevalence of vitamin D deficiency. A cross-sectional survey was conducted among 132 patients (1-18 years of age) visiting the paediatric outpatient department. Serum levels of 25(OH)D were measured using high-performance liquid chromatography. Cut-off levels of 30 and 50 nmol/l for serum 25(OH)D were evaluated. One third of the patients had serum 25(OH)D levels below 30 nmol/l, and half of the study population had serum levels below 50 nmol/l. Non-Western immigrants had an increased risk for vitamin D deficiency compared to their native Dutch peers [25(OH)D of <30 nmol/l, p = 0.03, odds ratio (OR) 3.87 (95 % confidence interval (CI) 1.13-13.29); 25(OH)D of <50 nmol/l, p = 0.02, OR 3.57 (95 % CI 1.26-10.14)] with the highest risk for first-generation non-Western immigrants., Conclusion: Vitamin D deficiency in the paediatric population is still a matter of concern in the Netherlands, in particular among first-generation non-Western immigrants. We therefore strongly recommend vitamin D supplementation for all non-Western immigrants, regardless of age, skin type or season. Health-care staff who work with non-Western immigrants should be aware of the prevalence and implications of vitamin D deficiency.

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 © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Hypothyroidism is associated with normocytic anaemia. Indeed, a limited number of studies have shown significant associations between free thyroxin (T4) and erythrocyte indices. These studies did not include vitamin B12, folic acid, iron and renal function in the analyses. We therefore studied the association between thyroid hormones and erythrocyte indices in a population-based cohort of older euthyroid subjects, with adjustment for major confounding parameters., Design: Data, including thyroid hormones and erythrocyte indices, are from the Longitudinal Aging Study Amsterdam (LASA), an ongoing cohort study on predictors and consequences of changes in health in the ageing population in the Netherlands. Multivariable linear regression analyses were applied to study the cross-sectional associations between free T4, thyroid stimulating hormone (TSH) and erythrocyte indices (haemoglobin content, haematocrit, mean cell volume (MCV) and erythrocyte count) in a euthyroid sub-sample. The final models were adjusted for vitamin B12, folic acid, iron levels and renal function., Results: In 708 euthyroid older subjects, an increase of 5pmol/L free T4 was associated with a mean increase of 0.12mmol/L or 0.19g/dL of haemoglobin, 0.068 10(12)/L erythrocytes and 0.006L/L haematocrit (P=0.007, P=0.005, P=0.001, respectively). Free T4 was not significantly associated with MCV (P>0.05). TSH appeared not to be associated with any of the erythrocyte indices (all P>0.05)., Conclusions: In a cohort of older subjects, free T4, but not TSH, was associated with erythrocyte indices, confirming the role of thyroid hormones in the regulation of erythropoiesis., (Copyright © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Context: Vitamin D receptor (VDR) polymorphisms are associated with a variety of diseases, which may translate into an effect on mortality., Objective: To investigate the associations between VDR gene variants and mortality among older people., Design: The analyses were conducted in a population-based, prospective cohort of the Longitudinal Aging Study Amsterdam. Adequate DNA analysis was performed in 923 men and women (≥65 years). We aimed to assess the associations between mortality and the VDR polymorphism FokI, three haplotypes of the Cdx2 and GATA polymorphisms, and three haplotypes of the BsmI, ApaI, and TaqI polymorphisms., Results: During the median follow-up of 10.7 years, 480 participants deceased (51%). Homozygosity for the Cdx2-GATA haplotype 1 allele was associated with a 30% higher mortality risk compared to the absence of alleles (hazard ratios (HR) 1.30, 95% confidence intervals (CI) 1.01-1.68). Adjustment for cardiovascular risk factors and 25-hydroxyvitamin D levels did not affect this HR. The number of copies of the Cdx2-GATA haplotype 1 allele was associated, although not significantly, with an increased risk of osteoporotic fractures (0 copies=reference, HR, 95% CI: 1 copy 2.01, 0.99-4.07 and 2 copies 1.81, 0.87-4.18). After adjustment for osteoporotic fractures, homozygosity for the Cdx2-GATA haplotype 1 allele was no longer associated with higher mortality risk (HR 1.08, 95% CI 0.83-1.41)., Conclusions: The Cdx2-GATA haplotype 1 allele was related to increased mortality risk, which may be partly explained by osteoporotic fractures. As the biological mechanism is uncertain and this study size is limited, our results should be interpreted as hypothesis generating.

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., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Context: Numerous studies have investigated the effect of serum IGF-I concentration on aging and different aging-related diseases, e.g. cardiovascular disease (CVD) and cancer. Decreased as well as increased levels have been reported to be associated with reduced life expectancy in humans., Objective: This study investigates the association of serum IGF-I concentration with all-cause and cause-specific mortality of community-dwelling older persons and the development of CVD and cancer., Design, Setting, and Participants: Data were used from the Longitudinal Aging Study Amsterdam (LASA), an ongoing multidisciplinary cohort study in the general Dutch population of older persons (≥65 yr old) where serum IGF-I was measured (n = 1273). The mortality information was ascertained using the International Classification of Diseases, 10th revision, and the presence or absence of CVD and cancer by self-reports with a follow-up of 11.6 yr., Main Outcome Measure: We measured all-cause, CVD, and cancer mortality and nonfatal CVD and cancer., Results: Fully adjusted Cox proportional hazards models demonstrated an increased risk of all-cause mortality for older persons with IGF-I values in the lowest quintile as compared to the middle quintile [hazard ratio (HR), 1.28; 95% confidence interval (CI), 1.01-1.63]. A more than 2-fold increased risk of CVD mortality was revealed for both low-normal (HR, 2.39; 95% CI, 1.22-4.66) and high-normal (HR, 2.03; 95% CI, 1.02-4.06) IGF-I values. Significant associations of serum IGF-I with nonfatal CVD and fatal and nonfatal cancer were not observed., Conclusions: Results suggest a U-shaped relationship between IGF-I level and mortality, with fatal CVD as the most critical outcome in community-dwelling older persons.

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 (>or=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.

The aim of this prospective study was to develop a risk score, based on putative risk factors in current guidelines, which can be used to identify women at high risk of fractures in general practice. The study sample included 4157 women >/=60 yr of age (mean +/- SD: 74.1 +/- 9.1 yr), with a median follow-up of 8.9 yr of the Rotterdam Study (ERGO), and 762 women >/=65 yr of age (mean +/- SD: 76.0 +/- 6.7.yr), with a median follow-up of 6.0 yr of the Longitudinal Aging Study Amsterdam (LASA). Potential risk factors were those proposed in risk scores of three recent guidelines on osteoporosis: age, family history of fractures, prior fracture, low body weight/body mass index (BMI), serious immobility, rheumatoid arthritis, current smoking, alcohol consumption >2 units daily, prevalent vertebral fracture, and systemic corticosteroid use. Five-year absolute risk of hip fracture was 3.9% in the Rotterdam Study and 3.1% in LASA, and 10-yr absolute risk of hip fracture was 8.4% in the Rotterdam Study. Using Cox regression analysis, age (70-79 and 80+ versus <60-69) and four other risk factors were included in the risk profiles of hip fractures and fragility fractures: any prior fracture after age 50, body weight <64 kg, use of a walking aid as a proxy measure of serious immobility, and current smoking. Estimated 10-yr absolute risk of hip fracture ranged from 1.4% in women, age 60-69 years, without any of these predictors to 29% in women, >/=80 yr of age, having two or more positive risk factors. A simple risk score can satisfactorily identify older women at high risk of osteoporotic fractures in general practice. Future studies are needed to validate this score.

Several guidelines on osteoporosis have proposed algorithms to identify persons at high risk of fractures. Although these algorithms include well-known risk factors, it is not clear how they can best be operationalized for use in general practice. The aim of this study was to compare the predictive performance of different operationalizations of four categories of risk factors for fractures that can be used in general practice. This study included 4157 women of > or =60 yr of age (mean +/- SD: 74.1 +/- 9.1 yr) with a median follow-up of 8.9 yr of the Rotterdam Study and 762 women of > or =65 yr of age (mean +/- SD: 76.0 +/- 6.7.yr) with a median follow-up of 6.0 yr of the Longitudinal Aging Study Amsterdam (LASA). At baseline, information on four categories of risk factors was obtained, including (1) family history of hip fractures, (2) type of prior fractures, (3) low body weight/body mass index (BMI), and (4) mobility impairment. The occurrence of fragility fractures, including hip, pelvic, humerus, and wrist fractures, was used as outcome measure. We quantified the predictive performance of each risk factor by a chi(2) statistic, calculated as the difference in -2 Log likelihood attributable to the risk factor, with adjustment for age and other risk factors. In the Rotterdam Study, 399 fragility fractures occurred during 31,472 person-years (PY) of follow-up. In this study, any prior fracture in the past 5 yr (chi(2) = 6; p = 0.02), body weight < 64 kg (versus > or =64 kg; chi(2) = 6.7; p = 0.01), BMI < 22 kg/m(2) (versus > or =22 kg/m(2); chi(2) = 8.7; p = 0.003), and use of a walking aid (chi(2) = 7.5; p = 0.004) were the most practical operationalizations of the risk factor categories, after adjustment for age and other risk factors. In LASA, 52 fragility fractures occurred during 3935 PY of follow-up. Associations were similar as in the Rotterdam Study, except that low body weight and BMI were not associated with fragility fracture. None of the usual operationalizations of family history of hip fractures was independently associated with fragility fracture in either study. Prior osteoporotic fracture, body weight <64 kg, a BMI <22 kg/m(2), and the use of a walking aid are practical operationalizations of risk factors for fragility fractures. On the basis of the results of this study, a simple, practical algorithm can be developed for use in general practice.

Background: Anti-Müllerian hormone (AMH) inhibits primordial follicle recruitment in the mouse ovary. We hypothesize that in women AMH signaling also regulates the usage of the primordial follicle pool and hence influences the onset of menopause. Since age at menopause has a strong genetic component, we investigated the role of AMH signaling using a candidate gene approach., Methods: In two large population-based cohorts of Dutch post-menopausal women (n = 2381 and n = 248), we examined the association between two polymorphisms, one in the AMH gene and one in the AMH type II receptor (AMHR2) gene, and natural age at menopause., Results: The AMH Ile(49)Ser polymorphism (rs10407022) was not associated with age at menopause in either cohort. In the Rotterdam cohort, the AMHR2 -482 A > G polymorphism (rs2002555) was associated with age at menopause in interaction with the number of offspring (P = 0.001). Nulliparous women homozygous for the G-allele entered menopause 2.6 years earlier compared with nulliparous women homozygous for the A-allele (P = 0.005). In the LASA cohort, women with the G/G genotype tended to enter menopause 2.8 years earlier compared with the A/A genotype (P = 0.063)., Conclusions: The observed association of the AMHR2 -482 A > G polymorphism with natural age at menopause suggests a role for AMH signaling in the usage of the primordial follicle pool in women.

Background: Falls frequently occur in the elderly and are a major cause of morbidity and mortality., Objective: The objective of the study was to prospectively investigate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and risk of recurrent falling in older men and women., Design: This was a prospective cohort study., Setting: An age- and sex-stratified random sample of the Dutch older population was determined., Subjects: Subjects included 1231 men and women (aged 65 yr and older) participating in the Longitudinal Aging Study Amsterdam., Measurements: Baseline serum 25(OH)D was determined by a competitive protein binding assay. During 1 yr, falls were prospectively recorded by means of a fall calendar., Results: Low 25(OH)D (<10 ng/ml) was associated with an increased risk of falling. After adjustment for age, sex, education level, region, season, physical activity, smoking, and alcohol intake, the odds ratios (95% confidence interval) were 1.78 (1.06-2.99) for subjects who experienced two falls or more as compared with those who did not fall or fell once and 2.23 (1.17-4.25) for subjects who fell three or more times as compared with those who fell two times or less. There was a statistically significant effect modification by age, and stratified analyses (<75 and > or = 75 yr) showed that the associations were particularly strong in the younger age group; the odds ratios (95% confidence interval) were 5.21 (2.03-13.40) for two falls or more and 4.96 (1.52-16.23) for three falls or more., Conclusions: Poor vitamin D status is independently associated with an increased risk of falling in the elderly, particularly in those aged 65-75 yr.