Geriatric Syndromes Frequently (Co)-Occur in Geriatric Rehabilitation Inpatients: Restoring Health of Acutely Unwell Adults (RESORT) and Enhancing Muscle Power in Geriatric Rehabilitation (EMPOWER-GR).

OBJECTIVE: To determine the prevalence and co-occurrence of common geriatric syndromes in geriatric rehabilitation inpatients. DESIGN: Restoring Health of Acutely Unwell Adults (RESORT) and Enhancing Muscle Power in Geriatric Rehabilitation (EMPOWER-GR) are observational, longitudinal cohorts. SETTING: Geriatric rehabilitation. PARTICIPANTS: Geriatric rehabilitation inpatients (N=1890 and N=200). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Geriatric syndromes included polypharmacy, multimorbidity (Cumulative Illness Rating Scale), cognitive impairment, depression (Hospital Anxiety and Depression Scale/Geriatric Depression Scale), malnutrition (Global Leadership Initiative on Malnutrition), functional limitation (Katz index), falls, physical frailty (Fried), and sarcopenia (European Working Group on Sarcopenia in Older People 2). RESULTS: Inpatients in RESORT (R) (N=1890, 56% females) had a median age of 83.4 years (interquartile range [IQR], 77.6-88.4) and in EMPOWER-GR (E) (N=200, 57% females) of 79.8 years (IQR, 75.0-85.9). Polypharmacy (R, 82.2%; E, 84.0%), multimorbidity (R, 90.4%; E, 85.5%), functional limitation (R, 96.0%; E, 76.5%), and frailty (R, 91.8%; E, 92.2%) were most prevalent. Most inpatients had ≥5 geriatric syndromes at admission in both cohorts (R, 70.0%; E, 72.4%); few inpatients had only 1 (R, 0.4%; E, 1.5%) or no geriatric syndrome (R, 0.2%; E, 0.0%). Geriatric syndromes did not occur in isolation (without other syndromes), except for multimorbidity (R, 1%; E, 5%), functional limitation (R, 3%; E, 2%), falls (R, 0%; E, 4%), and frailty (R, 2%; E, 5%), which occurred in isolation in some inpatients; sarcopenia did not. CONCLUSIONS: Geriatric syndromes are highly prevalent at admission to geriatric rehabilitation, with a median of 5 co-occurring syndromes. Implications for diagnosis and intervention potential should be further addressed.

High Sarcopenia Awareness Contrasts a Lack of Clinical Implementation Among Geriatric Rehabilitation Health Care Professionals in the Netherlands: EMPOWER-GR.

BACKGROUND AND PURPOSE: Despite being associated with serious adverse outcomes, such as mortality, sarcopenia remains largely undiagnosed in older individuals. This study aimed to assess the awareness, practices, and barriers and enablers to clinical implementation of sarcopenia diagnosis and treatment among geriatric rehabilitation health care professionals in the Netherlands. METHODS: As part of EMPOWER-GR, a cross-sectional survey among geriatric rehabilitation health care professionals working in the Netherlands was undertaken between September 23, 2020, and January 28, 2021. Professionals were recruited via a geriatric rehabilitation care provider, health care professional associations, professional networks of the research team, and social media. Descriptive statistics were used to assess the study outcomes. RESULTS AND DISCUSSION: Of the 501 geriatric rehabilitation health care professionals, 12.2% were physicians, 23.0% physical therapist/occupational therapists, 30.3% dietitians, 19.6% nurses, and 11.0% health care assistants. The concept of sarcopenia was known by 83.8% of the participants, 92.5% correctly identified sarcopenia as low muscle mass and strength (and low physical performance), and 73.8% identified sarcopenia as very important in the management of older adults admitted for rehabilitation. Although 26.2% and 18.9% of the participants reported screening and diagnosing sarcopenia, respectively, in their current practice, only 3.0% adequately used the (revised) definition of the European Working Group on Sarcopenia in Older People. When sarcopenia has been diagnosed, 65.0% reported initiating treatment consisting of resistance exercise training (78.7%), food fortification/high-energy or protein diet (85.4%), and oral nutritional supplements (70.4%). Most important barriers to screening and diagnosis were lack of knowledge, access to tools, and equipment and time, while enablers were protocol implementation, access to training, and clear responsibilities. CONCLUSIONS: Sarcopenia awareness is high among geriatric rehabilitation health care professionals in the Netherlands, but adequate screening and diagnosis is almost nonexistent in current clinical practice, which hampers interventions. Better knowledge, clear responsibilities, and access to tools and protocols, as well as prioritization, are needed for sarcopenia to be diagnosed and treated in geriatric rehabilitation in the Netherlands.

Sarcopenia knowledge of geriatric rehabilitation patients is low while they are willing to start sarcopenia treatment: EMPOWER-GR.

BACKGROUND: Sarcopenia is prevalent in 20-50% of geriatric rehabilitation inpatients and is associated with functional dependence and mortality. The aim is to assess knowledge of geriatric rehabilitation inpatients on sarcopenia and their willingness and perceived barriers to start treatment. METHODS: Enhancing Muscle POWER in Geriatric Rehabilitation (EMPOWER-GR) is an observational cohort of geriatric rehabilitation inpatients in Amsterdam, the Netherlands. Knowledge of sarcopenia, willingness and perceived barriers to treatment were assessed with a survey among inpatients. Importance of and self-perceived muscle health were rated using a visual analogue scale from 0 to 10. Descriptive statistics were used. RESULTS: Inpatients' (n = 157, 59.9% female) mean age was 80.5 years (SD 7.3). Sarcopenia (European Working Group on Sarcopenia in Older People 2) prevalence was 21.7%. Five inpatients (3.2%) had heard of sarcopenia and had knowledge of its definition. Median muscle health was rated as 6 (interquartile range: 4-7). After explanation of treatment options, 67.1% were willing to start resistance exercise training (RET), 61.1% a high-protein diet and 55.7% oral nutritional supplements (ONS). Inpatients with sarcopenia were less willing (51.6%) to start a high-protein diet compared with inpatients without sarcopenia (77.8%) (P = 0.002); there was no difference for RET and ONS. Most reported barriers to treatment were ONS dislike (17.0%), too many other health issues (13.6%), doubts about treatment effectiveness/importance (12.9%) and RET intensity/difficulty (10.2%). CONCLUSIONS: Knowledge of sarcopenia was low, while the majority of inpatients showed willingness to start treatment. A dislike of ONS, RET difficulty and too many other health issues may reduce willingness to start treatment. Education is important to increase sarcopenia-related health issues in geriatric rehabilitation inpatients.

Nutritional Care Practices in Geriatric Rehabilitation Facilities across Europe: A Cross-Sectional Study.

Many patients in geriatric rehabilitation (GR) are physically frail at the time of admission and suffer from malnutrition and sarcopenia, which may worsen rehabilitation outcomes. This study aims to obtain insight into the current nutritional care practices in GR facilities across Europe. METHODS: In this cross-sectional study, a questionnaire focused on nutritional care practices in GR was distributed across experts in EUGMS member countries. Data were analyzed by using descriptive statistics. RESULTS: In total, 109 respondents working in 25 European countries participated, and the results showed that not all GR patients were screened and treated for malnutrition, and not all participants used (inter)national guidelines when performing nutritional care. The results also showed variations across European geographical areas related to screening and treatment of malnutrition, sarcopenia, and frailty. Even though the participants underlined the importance of dedicating time to nutritional care, they experienced barriers in its implementation, which were mostly due to a lack of resources. CONCLUSION: As malnutrition, sarcopenia, and frailty are often present in patients admitted to GR, in addition to being interrelated, it is recommended to develop an integrated approach to screening and treatment of all three clinical problems.

Sarcopenia, malnutrition and cognition affect physiotherapy frequency during geriatric rehabilitation: RESORT cohort.

BACKGROUND: Physiotherapy (PT) is important to optimize functional recovery in geriatric rehabilitation. The dose of PT received by inpatients during geriatric rehabilitation and the determinants of dose are unknown. OBJECTIVES: Describe PT dose in terms of total number of sessions, frequency, duration and type of sessions, and inpatient characteristics determining the frequency of PT in geriatric rehabilitation. METHODS: The observational, longitudinal REStORing health of acutely unwell adulTs (RESORT) cohort consists of geriatric inpatients undergoing rehabilitation including PT (Melbourne, Australia). Ordinal regression was used to assess the determinants of PT frequency (total number of sessions divided by length of stay in weeks). Malnutrition, frailty and sarcopenia were diagnosed according to the Global Leadership Initiative on Malnutrition criteria, Clinical Frailty Scale and revised definition of the European Working Group on Sarcopenia in Older People respectively. RESULTS: Of the 1890 participants, 1799, median (quartile 1; quartile 3) age 83.4 (77.6; 88.4) years, 56% females received PT and were admitted for at least 5 days. Median total number of PT sessions was 15 (8; 24); median frequency was 5.2 sessions per week (3.0; 7.7); and duration was 27 (22; 34) minutes per session. Higher disease burden, cognitive impairment, delirium, higher anxiety and depression scores, malnutrition, frailty and sarcopenia were associated with a lower PT frequency. Older age, female sex, musculoskeletal reason for admission, greater independence in (instrumental) activities of daily living and handgrip strength were associated with a higher PT frequency. CONCLUSIONS: PT frequency varied widely with a median of 1 session per working day. PT frequency was lowest in participants with poorest health characteristics.

Feasibility of bioelectrical impedance analysis in routine clinical care to assess body composition in geriatric rehabilitation inpatients: RESORT.

BACKGROUND: Sarcopenia is prevalent in 20-50% of geriatric rehabilitation inpatients, but it is often undiagnosed. AIMS: The aim of the study is to evaluate the feasibility of bioelectric impedance analysis (BIA) to measure muscle mass in routine clinical care in a cohort of geriatric rehabilitation inpatients. METHODS: REStORing Health of acutely unwell adulTs (RESORT) is an observational, longitudinal inception cohort of geriatric rehabilitation inpatients. BIA was implemented at admission and discharge as routine care performed by nursing staff. BIA feasibility was defined as completion rate (low ≤ 25%, moderate > 25- ≤ 50%, good > 50- ≤ 75%, excellent > 75%), reasons for non-completion and need for remeasurement. Clinical characteristics associated with BIA completion and remeasurements were assessed. RESULTS: Patients (n = 1890, 56% females) had a median age of 83.4 years (interquartile range: [77.6-88.4]). Of the total cohort, 5.7% had a contraindication (pacemaker/other electronic medical device) for BIA at admission and 4.5% at discharge. BIA was completed in 77.1% of patients eligible for BIA at admission and 63.2% at discharge indicating good feasibility; remeasurement was required in 7.4 and 6.9%, respectively; 5.9% had a medical reason preventing BIA completion at admission and 3.7% at discharge. Refusal and technical issues occurred in 1.6 and 0.7% at admission and 2.1 and 1.8% at discharge. Reason for non-completion was unknown/missing in 14.7% at admission and 28.6% at discharge. Worse functional and physical performance was associated with BIA non-completion and remeasurement. CONCLUSIONS: BIA in routine clinical care in geriatric rehabilitation inpatients is feasible; completion rates may be enhanced further by reviewing barriers and enablers.

Handgrip strength rather than chair stand test should be used to diagnose sarcopenia in geriatric rehabilitation inpatients: REStORing health of acutely unwell adulTs (RESORT).

BACKGROUND: according to the revised sarcopenia definition proposed by the European Working Group on Sarcopenia in Older People (EWGSOP2) and revised definition of the Asian Working Group for Sarcopenia (AWGS2019), handgrip strength (HGS) and chair stand test (CST) can be used interchangeably as initial diagnostic measures. OBJECTIVE: to assess the agreement between sarcopenia prevalence, using either HGS or CST, and their association with adverse outcomes in geriatric rehabilitation inpatients. METHODS: REStORing health of acutely unwell adulTs is an observational, longitudinal cohort of geriatric rehabilitation inpatients. Cohen's kappa (κ) was used to assess the agreement between sarcopenia prevalence (no, probable and confirmed and severe sarcopenia) according to EWGSOP2 and AWGS2019 using either HGS or CST. Associations between HGS and CST and readmission, institutionalisation and mortality were assessed by binomial regression. RESULTS: patients (n = 1,250, 57% females) had a median age of 83.1 years (interquartile range: [77.5-88.3]). There was no agreement between probable sarcopenia prevalence using HGS or CST for EWGSOP2 and AWGS2019, respectively (HGS: 70.9% and 76.2%; CST: 95.5% and 98.4%; κ = 0.08 and 0.02). Agreement between confirmed and severe sarcopenia prevalence using either HGS or CST was strong to almost perfect. HGS was associated with 3-month institutionalisation and 3-month and 1-year mortality, whereas CST was not associated. CONCLUSIONS: HGS and CST cannot be used interchangeably as diagnostic measures for probable sarcopenia in geriatric rehabilitation inpatients. CST is not useful to predict adverse outcomes in geriatric rehabilitation inpatients.

Combating sarcopenia in geriatric rehabilitation patients: study protocol of the EMPOWER-GR observational cohort, sarcopenia awareness survey and randomised controlled feasibility trial.

INTRODUCTION: Sarcopenia is highly prevalent in geriatric rehabilitation patients. Resistance exercise training (RET) combined with protein supplementation is recommended to increase muscle mass and strength in older adults. However, sarcopenia awareness, feasibility to diagnose and treat sarcopenia, and efficacy of treatment in geriatric rehabilitation patients remain to be established. METHODS AND ANALYSIS: Enhancing Muscle POWER in Geriatric Rehabilitation (EMPOWER-GR) encompasses four pillars: (1) an observational cohort study of 200 geriatric rehabilitation inpatients determining sarcopenia prevalence, functional and nutritional status at admission; (2) a survey among these 200 patients and 500 healthcare professionals and semistructured interviews in 30 patients and 15 carers determining sarcopenia awareness and barriers/enablers regarding diagnostics and treatment; (3) a feasibility, single-centre, randomised, controlled, open-label, two parallel-group trial in 80 geriatric rehabilitation patients with sarcopenia. The active group (n=40) receives three RET sessions per week and a leucine and vitamin D-enriched whey protein-based oral nutritional supplement two times per day in combination with usual care for 13 weeks. The control group (n=40) receives usual care. Primary outcomes are feasibility (adherence to the intervention, dropout rate, overall feasibility) and change from baseline in absolute muscle mass at discharge and week 13. Secondary outcomes are feasibility (participation rate) and change from baseline at discharge and week 13 in relative muscle mass, muscle strength, physical and functional performance, mobility, nutritional status, dietary intake, quality of life and length of stay; institutionalisation and hospitalisation at 6 months and mortality at 6 months and 2 years; (4) knowledge sharing on sarcopenia diagnosis and treatment. ETHICS AND DISSEMINATION: Ethical exemption was received for the observational cohort study, ethics approval was received for the randomised controlled trial. Results will be disseminated through publications in scientific peer-reviewed journals, conferences and social media. TRIAL REGISTRATION NUMBER: NL9444.

Effects of Nutritional Interventions on Nutritional and Functional Outcomes in Geriatric Rehabilitation Patients: A Systematic Review and Meta-Analysis.

OBJECTIVES: It has been recognized that nutritional interventions play a role in improving the nutritional and functional status of older persons. This systematic review summarizes the evidence on nutritional and functional outcomes of nutritional interventions alone or in combination with physical exercise in geriatric rehabilitation patients. DESIGN: Eight electronic databases were searched until July 1, 2019 to identify nutritional intervention studies in patients aged ≥60 years who were admitted to geriatric rehabilitation. A meta-analysis was performed to quantify intervention effects on serum albumin, muscle mass, and hand grip strength (HGS). RESULTS: A total of 1962 studies were screened and 13 included in the systematic review. Studies were heterogeneous in interventions (4 nutritional interventions, 6 physical exercise + nutritional intervention, 1 timing of protein provision, 1 exercise + dietary advice, 1 nutrition-related nursing care) and outcomes. Among the 9 interventions that tested oral nutritional supplements (ONS) with protein, with or without exercise, 7 studies reported protein intake and 6 showed increased protein intakes, 2 of 5 studies showed increased albumin levels, and 5 of 9 reported an improvement in functional outcomes (BI, Functional Independence Measure, mobility). Meta-analyses showed no significant intervention effects on albumin [standardized mean difference (SMD) 0.45, 95% confidence interval (CI) -0.14, 1.04 (4 studies)], muscle mass [mean difference (MD) 2.14 kg, 95% CI -2.17, 6.45 (3 studies)], and HGS [SMD -0.04, 95% CI -0.55, 0.63 (3 studies)], but was based on a very limited number of studies. CONCLUSIONS AND IMPLICATIONS: Only a limited number of studies with heterogeneous nutritional interventions and outcomes were available in the geriatric rehabilitation population. Studies that included ONS improved nutritional outcomes, especially protein intake and albumin levels. Functional outcomes improved in the majority of reporting studies. This indicates benefits of protein supplementation, with or without exercise, in this population. Future well-designed and well-powered clinical trials are needed to clarify existing controversial aspects.

EuGMS survey on structures of geriatric rehabilitation across Europe.

PURPOSE: Geriatric rehabilitation provides effective multidisciplinary treatment for older people who show symptoms of relevant and potentially reversible functional decline. The aim of this study is to provide an overview on structures of geriatric rehabilitation across Europe. METHODS: All European Geriatric Medicine Society (EuGMS) Full board members, each representing one member state of the society, were asked to complete an online questionnaire about the current structure of geriatric rehabilitation in their country. RESULTS: Thirty-one out of 33 EuGMS Full Board members participated in this questionnaire. Geriatric rehabilitation was officially recognized in 65% (20/31) of participating countries while 29% (9/31) had no geriatric rehabilitation services in their country. In countries with geriatric rehabilitation, the number of available beds varied widely (0-70/100,000 inhabitants). Average length of stay varied from 7 to 65 days. The estimated mean age of the patients in geriatric rehabilitation was 80 years, with most patients being older than 70 years. Six countries had no specified lower age limit and no country had an upper age limit. 42% (13/31) of countries reported having national or local guidelines and 35% (11/31) had a benchmarking or audit system established. Most participants responded positively about the prospects for improvement in the field. CONCLUSION: We observed major differences among EuGMS member countries with regard to the availability of geriatric rehabilitation and how it was organized. Despite various barriers in most countries, future improvement in geriatric rehabilitation services is anticipated.

The prevalence and health burden of malnutrition in Belgian older people in the community or residing in nursing homes: results of the NutriAction II study.

INTRODUCTION: In 2008, the NutriAction study showed that (risk of) malnutrition was highly prevalent (57%) among Belgian older people living in the community or in a nursing home. In 2013, this study was repeated to re-evaluate the occurrence of malnutrition, as well as mobility problems and dependence in activities of daily living (ADL). METHODS: Health care professionals (HCPs) associated with homecare organizations and nursing homes across Belgium were invited to screen their patients and complete an online questionnaire. Nutritional status, presence of pre-specified comorbidities, mobility, and ADL dependency were assessed. RESULTS: In total, 3299 older patients were analysed: 2480 (86.3 ± 6.3 years) nursing home (NH) residents and 819 (82.7 ± 6.1 years) community dwelling (CD). Overall, 12% was malnourished (MNA-SF score < 8) and 44% was at risk of malnutrition (MNA-SF 8-11). The highest prevalence of (risk of) malnutrition was observed in NHs (63%) and in patients with dementia (CD: 68%; NH: 82%) or depression (CD: 68%; NH: 79%). Of all malnourished individuals, 49% was recognized as malnourished by HCPs and 13% of the malnourished recognized themselves as such. Mobility (stair climbing and walking) and ADL dependency (Belgian KATZ score) were impaired in older people with (risk of) malnutrition in comparison with individuals with normal nutritional status (p < 0.001). DISCUSSION: Despite public awareness initiatives, the prevalence of malnutrition remained stable among Belgian older people seen by HCPs in the period 2008-2013. Moreover, malnutrition is not well recognized. CONCLUSION: Under-recognition of malnutrition is problematic, because associated loss of mobility and independence may accelerate the transformation of frailty into disability in older people.

Correction to: The prevalence and health burden of malnutrition in Belgian older people in the community or residing in nursing homes: results of the NutriAction II study.

In the original publication, table row alignment was incorrectly formatted for all the tables. The corrected tables are given below.

CYP2C9 Genotypes Modify Benzodiazepine-Related Fall Risk: Original Results From Three Studies With Meta-Analysis.

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.

Folate and Vitamin B12-Related Biomarkers in Relation to Brain Volumes.

AIM: We investigated cross-sectional associations between circulating homocysteine, folate, biomarkers of vitamin B12 status and brain volumes. We furthermore compared brain volumes of participants who received daily folic acid and vitamin B12 supplementation with participants who did not. METHODS: Participants of the B-PROOF study (n = 2919) were assigned to 400 µg folic acid and 500 µg vitamin B12, or a placebo. After two years of intervention, T1-weighted magnetic resonance imaging (MRI) scans were made in a random subsample (n = 218) to obtain grey and white matter volume, and total brain volume (TBV). Plasma homocysteine, serum folate, vitamin B12, holotranscobalamin, and methylmalonic acid concentrations were measured. RESULTS: Multiple linear regression analyses showed inverse associations between plasma homocysteine with TBV (ß = -0.91, 95% CI -1.85-0.03; p = 0.06) and between serum folate and TBV (ß = -0.20, 95% CI -0.38, -0.02; p = 0.03). No significant associations were observed for serum vitamin B12 and holotranscobalamin. Fully adjusted ANCOVA models showed that the group that received B-vitamins had a lower TBV (adjusted mean 1064, 95% CI 1058-1069 mL) than the non-supplemented group (1072, 95% CI 1067-1078 mL, p = 0.03). CONCLUSIONS: Results were contradictory, with higher Hcy levels associated with lower TBV, but also with higher folate levels associated with lower TBV. In addition, the lack of a baseline measurement withholds us from giving recommendations on whether folic acid and vitamin B12 supplementation will be beneficial above and beyond normal dietary intake for brain health.

Effects of Two-Year Vitamin B12 and Folic Acid Supplementation on Depressive Symptoms and Quality of Life in Older Adults with Elevated Homocysteine Concentrations: Additional Results from the B-PROOF Study, an RCT.

Lowering elevated plasma homocysteine (Hcy) concentrations by supplementing vitamin B12 and folic acid may reduce depressive symptoms and improve health-related quality of life (HR-QoL) in older adults. This study aimed to test this hypothesis in a randomized controlled trial. Participants (N = 2919, ≥65 years, Hcy concentrations ≥12 µmol/L) received either 500 µg vitamin B12 and 400 µg folic acid daily or placebo for two years. Both tablets contained 15 µg vitamin D3. Depressive symptoms were measured with the Geriatric Depression Scale-15 (GDS-15). HR-QoL was assessed with the SF-12 Mental and Physical component summary scores and the EQ-5D Index score and Visual Analogue Scale. Differences in two-year change scores were analyzed with Analysis of Covariance (ANCOVA). Hcy concentrations decreased more in the intervention group, but two-year change scores of the GDS-15 and three of four HR-QoL measures did not differ between groups. The EQ-5D Index score declined less in the intervention group than in the placebo group (mean change 0.00 vs. -0.02, p = 0.004). In conclusion, two-year supplementation with vitamin B12 and folic acid in older adults with hyperhomocysteinemia showed that lowering Hcy concentrations does not reduce depressive symptoms, but it may have a small positive effect on HR-QoL.

Effect of vitamin B12 and folic acid supplementation on biomarkers of endothelial function and inflammation among elderly individuals with hyperhomocysteinemia.

B-vitamin trials failed to demonstrate beneficial effects on cardiovascular outcomes, but hyperhomocysteinemia still stands out as an independent cardiovascular risk factor, particularly in elderly individuals. B-vitamins may influence early vascular dysfunction, such as endothelial dysfunction, or may have adverse effects, for example on inflammation. We investigated the effect of B-vitamins on endothelial function and inflammation within an interventional study. This study was conducted within the framework of the B-PROOF trial, which included 2919 hyperhomocysteinemic elderly individuals, who received daily vitamin B12 (500 µg) and folic acid (400 µg) or placebo for 2 years. Using an electrochemiluminescence platform, we measured intercellular adhesion molecule 1 (ICAM-1), vascular adhesion molecule 1 (VCAM-1), serum amyloid A (SAA), vascular endothelial growth factor (VEGF) and C-reactive protein (CRP) at baseline and follow-up in a subsample of 522 participants (271 intervention group; 251 placebo). Treatment effects were analyzed with ANCOVA. The participants had a mean age of 72 years, and 55% of them were male. At the 2-year follow-up, B-vitamins did not change the ICAM-1 (+36% change in the intervention group versus +32% change in the placebo group; p = 0.72), VCAM-1 (+27% vs +25%; p = 0.39), VEGF (-1% vs +4%; p = 0.40), SAA (+34% vs +38%; p = 0.85) or CRP levels (+26% vs +36%; p = 0.70) as compared to placebo. In conclusion, in elderly patients with hyperhomocysteinemia, vitamin B12 and folic acid are unlikely to influence either endothelial function or low-grade systemic inflammation. ClinicalTrials.gov Identifier: NCT00696514.

Relative importance of summer sun exposure, vitamin D intake, and genes to vitamin D status in Dutch older adults: The B-PROOF study.

BACKGROUND/OBJECTIVES: The prevalence of vitamin D deficiency among seniors is high. Whereas sun exposure, vitamin D intake, genes, demographics, and lifestyle have been identified as being important determinants of vitamin D status, the impact of these factors is expected to differ across populations. To improve current prevention and treatment strategies, this study aimed to explore the main determinants of vitamin D status and its relative importance in a population of community-dwelling Dutch older adults. METHODS/SUBJECTS: Serum 25-hydroxyvitamin D (25(OH)D) was measured in 2857 adults aged ≥65 years. Sun exposure was assessed with a structured questionnaire (n=1012), vitamin D intake using a Food Frequency Questionnaire (n=596), and data on genetic variation that may affect 25(OH)D status was obtained for 4 genes, DHCR7 (rs12785878), CYP2R1 (rs10741657), GC (rs2282679), and CYP24A1 (rs6013897) (n=2530). RESULTS: Serum 25(OH)D concentrations <50nmol/L were observed in 45% of the population; only 6% of these participants used vitamin D supplements. Sun exposure (being outside daily during summer: 66±25nmol/L vs not being outside daily during summer: 58±27nmol/L, P=0.02) and vitamin D intake (per unit µg/day during winter/spring: 3.1±0.75nmol/L, P<0.0001) were associated with higher 25(OH)D concentrations. Major allele carriers of SNPs related to DHCR7, CYP24A1, and GC, as well as CYP2R1 minor allele carriers had the highest 25(OH)D concentrations. Together, sun (R2=0.29), vitamin D intake (R2=0.24), and genes (R2=0.28) explained 35% (R2=0.35) of the variation in 25(OH)D concentrations during summer/autumn period, when adjusted for age, sex, BMI, education, alcohol consumption, smoking, physical activity, and self-rated health status (n=185). CONCLUSION: The investigated determinants explained 35% of 25(OH)D status. Of the three main determinants under study, sun exposure still appeared to be an important determinant of serum 25(OH)D in older individuals, closely followed by genes, and vitamin D intake. Given the low frequency of vitamin D supplement use in this population, promoting supplement use may be an inexpensive, easy, and effective strategy to fight vitamin D deficiency.

A Randomized Controlled Trial to Examine the Effect of 2-Year Vitamin B12 and Folic Acid Supplementation on Physical Performance, Strength, and Falling: Additional Findings from the B-PROOF Study.

Elevated homocysteine concentrations are associated with a decline in physical function in elderly persons. Homocysteine-lowering therapy may slow down this decline. This study aimed to examine the effect of a 2-year intervention of vitamin B12 and folic acid supplementation on physical performance, handgrip strength, and risk of falling in elderly subjects in a double-blind, randomized placebo-controlled trial. Participants aged ≥65 years with elevated plasma homocysteine concentrations [12-50 µmol/L (n = 2919)] were randomly assigned to daily supplementation of 500 µg vitamin B12, 400 µg folic acid, and 600 IU vitamin D3, or to placebo with 600 IU vitamin D3. Physical performance (range 0-12) and handgrip strength (kg) were measured at baseline and after 2 years. Falls were reported prospectively on a research calendar. Intention-to-treat (primary) and per-protocol (secondary) analyses were performed. Physical performance level and handgrip strength significantly decreased during the follow-up period, but this decline did not differ between groups. Moreover, time to first fall was not significantly different (HR: 1.0, 95% CI 0.9-1.2). Secondary analyses on a per-protocol base identified an interaction effect with age on physical performance. In addition, the treatment was associated with higher follow-up scores on the walking test (cumulative OR: 1.3, 95% CI 1.1-1.5). Two-year supplementation of vitamin B12 and folic acid was neither effective in reducing the age-related decline in physical performance and handgrip strength, nor in the prevention of falling in elderly persons. Despite the overall null-effect, the results provide indications for a positive effect of the intervention on gait, as well as on physical performance among compliant persons >80 years. These effects should be further tested in future studies.

Dietary Sources of Vitamin B-12 and Their Association with Vitamin B-12 Status Markers in Healthy Older Adults in the B-PROOF Study.

Low vitamin B-12 concentrations are frequently observed among older adults. Malabsorption is hypothesized to be an important cause of vitamin B-12 inadequacy, but serum vitamin B-12 may also be differently affected by vitamin B-12 intake depending on food source. We examined associations between dietary sources of vitamin B-12 (meat, fish and shellfish, eggs, dairy) and serum vitamin B-12, using cross-sectional data of 600 Dutch community-dwelling adults (≥65 years). Dietary intake was assessed with a validated food frequency questionnaire. Vitamin B-12 concentrations were measured in serum. Associations were studied over tertiles of vitamin B-12 intake using P for trend, by calculating prevalence ratios (PRs), and splines. Whereas men had significantly higher vitamin B-12 intakes than women (median (25th-75th percentile): 4.18 (3.29-5.38) versus 3.47 (2.64-4.40) µg/day), serum vitamin B-12 did not differ between the two sexes (mean ± standard deviation (SD): 275 ± 104 pmol/L versus 290 ± 113 pmol/L). Higher intakes of dairy, meat, and fish and shellfish were significantly associated with higher serum vitamin B-12 concentrations, where meat and dairy-predominantly milk were the most potent sources. Egg intake did not significantly contribute to higher serum vitamin B-12 concentrations. Thus, dairy and meat were the most important contributors to serum vitamin B-12, followed by fish and shellfish.

Higher Serum 25-Hydroxyvitamin D and Lower Plasma Glucose Are Associated with Larger Gray Matter Volume but Not with White Matter or Total Brain Volume in Dutch Community-Dwelling Older Adults.

BACKGROUND: Previous studies have shown beneficial associations between 25-hydroxyvitamin D [25(OH)D] status and cognitive performance, but results are inconclusive. Studies on 25(OH)D status and brain volumetric measures may provide more insight in the potential role of vitamin D in cognitive performance. OBJECTIVES: The aims of this study were to cross-sectionally investigate the association between vitamin D status and brain tissue volumes in 217 Dutch community-dwelling older adults aged ≥65 y and to examine whether surrogate markers of glucose homeostasis act as modifiers in these associations. METHODS: Serum 25(OH)D, plasma glucose, and plasma insulin were analyzed, serving as exposure measures. Estimates of total brain volume, gray matter volume, and white matter volume were obtained using MRI, serving as outcome measures. Associations of serum 25(OH)D, plasma glucose, and plasma insulin concentrations with brain tissue volumes were evaluated using multiple linear regression analyses. Potential effect modification by glucose homeostasis in the association between 25(OH)D and brain volumetric measures was examined by stratification and testing for interaction. RESULTS: After full adjustment, higher serum 25(OH)D concentrations and lower plasma glucose concentrations were associated with larger gray matter volume, [ß ± SE: 0.20 ± 0.08 mL (P = 0.02) and -3.26 ± 1.59 mL (P = 0.04), respectively]. There were no associations between serum 25(OH)D and plasma insulin concentrations with total brain volume and white matter volume. Furthermore, there was no evidence for a mediation or modification effect of plasma glucose on the associations between serum 25(OH)D and brain tissue volumes. CONCLUSION: Higher serum 25(OH)D and lower plasma glucose are associated with larger gray matter volume, but not white matter or total brain volume, in a population of Dutch adults aged ≥65 y. This trial was registered at clinicaltrials.gov as NCT00696514.