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The Systolic Blood Pressure Intervention Trial (SPRINT) compared the clinical outcomes between target systolic blood pressure (SBP) levels between 140 and 120 mmHg or lower. Both,the 2017 ACC/AHA and the 2018 ESC/ESH guidelines in hypertension are derived from the SPRINT trial and advise initiation and/or intensification of treatment at lower blood pressure thresholds. The ACC/AHA guidance supersedes the 2014 Eight Joint National Committee guideline (JNC-8) which advised initiation of treatment when the BP was 140/90 mmHg or higher; in adults 60 years or over, the target was 150/90 mmHg. Compared to JNC-8, the new guidelines lower the SBP target by 10 mmHg in patients under age of 60 years, and by 20 mmHg in the elderly. We performed a qualitative multi-dimensional analysis in order to answer two key questions: will the new guidelines deliver the stated benefits? and, will translation to the clinic be simple, risk-free, and affordable? A major investment by national healthcare administrations will be necessary for the initiation and support of this program but this decision can only be justified by a valid expectation of clinical benefit. At this time, a definitive answer is not available and a "wait and see" attitude appears appropriate and reasonable. In the interim, efforts are best directed to the immediate problem of untreated hypertension worldwide. [ABSTRACT FROM AUTHOR]

Objective: To independently assess the inter-rater reliability of the International Dementia Alliance (IDEAL) schedule in Ireland and to examine criterion validity for cognitive functioning and caregiver distress.Methods: Two raters independently completed the IDEAL schedule based on an interview with persons diagnosed with dementia and their informal caregivers. The Clinical Dementia Rating (CDR) scale and the Zarit Burden Interview were used as reference standards for criterion validity. Intraclass coefficients (ICCs) and correlations (Spearman's ρ) were derived.Results: ICCs for the IDEAL subdomains ranged from 0.77 to 1.00, indicating robust agreement between raters. Strong correlations between the CDR and the IDEAL cognitive functioning domain (ρ = 0.82) and overall summary score (ρ = 0.77) were observed. The Zarit Burden Interview and the IDEAL carer distress subdomain were moderately correlated (ρ = 0.56).Conclusion: This study confirmed that the IDEAL schedule is a valid and reliable instrument in the Irish population and further supports the international use of the IDEAL schedule. [ABSTRACT FROM AUTHOR]

Objectives: Neuropsychiatric symptoms (NPS) are highly prevalent in dementia, but effective pharmacotherapy without important side effects is lacking. This study aims to assess the efficacy and safety of oral tetrahydrocannabinol (THC) in the treatment of NPS in dementia.Design: Randomized, double-blind, placebo-controlled, repeated crossover trial, consisting of six treatment blocks of 2 weeks each.Setting: Two hospital sites in The Netherlands, September 2011 to December 2013.Participants: Patients with dementia and clinically relevant NPS.Intervention: Within each block THC (0.75 mg twice daily in blocks 1-3 and 1.5 mg twice daily in blocks 4-6) and placebo were administered in random order for 3 consecutive days, followed by a 4-day washout.Measurements: Primary outcome was change in Neuropsychiatric Inventory (NPI) score. Analyses were performed intention-to-treat. Data from all subjects were used without imputation. Sample size required for a power of 80% was 20 patients, because of repeated crossover.Results: 22 patients (15 men, mean age 76.4 [5.3] years) were included, of whom 20 (91%) completed the trial. THC did not reduce NPI compared to placebo (blocks 1-3: 1.8, 97.5% CI: -2.1 to 5.8; blocks 4-6: -2.8, 97.5% CI: -7.4 to 1.8). THC was well tolerated, as assessed by adverse event monitoring, vital signs, and mobility. The incidence of adverse events was similar between treatment groups. Four non-related serious adverse events occurred.Conclusions: This is the largest randomized controlled trial studying the efficacy of THC for NPS, to date. Oral THC did not reduce NPS in dementia, but was well tolerated by these vulnerable patients, supporting future higher dosing studies. [ABSTRACT FROM AUTHOR]

In a world where 12% of the population, and 22% of that of more developed regions, will be older than 65 years by 2030, new targeted programs and social protections will be needed for older people in many countries. As economic and human resources become more scarce, efficient instruments are needed to realize sustainable health care for these large populations of older subjects. To address this need a new assessment instrument was developed. The core of the instrument consists of focused geriatric assessment by a health or social care practitioner working in primary or community care, most often a nurse. The assessment data result in an efficiently targeted care and welfare action plan based on the patients' priorities This instrument was initially developed, tested and spread within Europe, and then in validation studies across all WHO regions of the world. Because of the urgent societal questions on quality and sustainability of primary health care, especially for older people, we briefly review and summarize the development and evidence base of the instrument, which was called EASY-Care Standard. In a series of studies across many populations it proved to have high acceptability, reliability, validity and cost-effectiveness. Therefore, EASY-Care has great potential as a universal tool for global use in promoting independence in old age, and can make an important contribution to the quality and sustainability of health and social care in our aging societies [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to assess the feasibility and reproducibility of a simple and nonobtrusive repeated sit-stand maneuver to assess cerebral autoregulation (CA) in healthy old subjects >70 years. In 27 subjects aged 76 (SD 4) years, we continuously measured blood pressure using photoplethysmography and cerebral blood flow velocity in the middle cerebral artery (transcranial Doppler ultrasonography) during 5min of sitting rest and again during repeated sit-stand maneuvers at 10 s (0.05Hz) and 5 s (0.1Hz) intervals. In 11 randomly selected subjects, these measurements were repeated after 3 months. Both maneuvers induced substantial periodic oscillations in pressure and flow. For example, the maneuvers at 0.05Hz increased the power spectral density (magnitude) of blood pressure and cerebral blood flow velocity oscillations with 16.3 (mm Hg)2 and 14.5 (cm/s)2, respectively (p <0.001). These larger oscillations led to an increase in transfer function coherence compared with spontaneous oscillations from 0.46 to 0.60 for 0.05Hz maneuvers and from 0.56 to 0.76 for 0.1Hz maneuvers (p <0.01), allowing for more confident assessment of CA through transfer function phase and gain. This increased coherence was not associated with improved reproducibility however. In conclusion, we were able to investigate CA in old patients using these repeated sit-stand maneuvers, which, compared with spontaneous oscillations, produced a stronger and more clinically relevant hemodynamic challenge for CA. (E-mail: j.claassen@ger.umcn.nl) [Copyright &y& Elsevier]

Objective: To examine the somatic complaints, functional impairment, and psychiatric comorbidity in elderly patients with medically unexplained symptoms (MUSs). Method: A consecutive case series of 37 patients referred for MUS to a multidisciplinary, outpatient clinic at a secondary care mental health center in the Netherlands. All patients underwent a standardized examination by a geriatrician, psychiatrist, and psychologist. Results: For three patients, a somatic explanation was found, and in two, their symptoms spontaneously resolved before a diagnosis could be made. Of the remaining 32 patients with MUS, depressive disorders were present in 18 (56%), anxiety disorders in 10 (31%), and substance use disorders in 6 patients (19%). Compared with nondepressed patients with MUS, depressed patients had more severe somatic symptoms, more psychological symptoms, and more functional impairment. Conclusions: As the authors found a high comorbidity with other psychiatric disorders in elderly patients with MUSs, a systematic psychiatric examination should be part of their multidisciplinary assessment. [ABSTRACT FROM AUTHOR]

Transcatheter aortic valve implantation (TAVI) has emerged as the preferred management strategy for elderly patients with severe symptomatic aortic valve stenosis. These patients are often at high risk of postoperative delirium (POD), which is associated with morbidity and mortality. Since POD may be prevented in a considerable part of these patients, identification of patients at risk is essential. The aim of current study was to identify geriatric assessment tools associated with delirium after TAVI, and long-term mortality. Consecutive patients were preoperatively assessed by a geriatrician between 2012 and 2017. Geriatric assessment tools consisted of cognitive, functional, mobility, and nutritional tests. POD was prospectively assessed during hospitalization after TAVI. Mortality tracking was performed by consulting municipal registries. A total of 511 patients were included. Median age was 80 [76-84] years, 44.8% (n = 229) were male, and 14.1% (n = 72) had a history of POD. Delirium was observed in 66 (12.9%) patients. Impaired mobility was the strongest geriatric assessment tool associated with POD (adjusted odds ratio, 2.1 [1.1-4.2], P =.028) and 2-year mortality (adjusted hazard ratio, 2.5 [1.4-4.5], P =.003). Two-year survival was reduced with more than 10% in patients with impaired mobility before TAVI (79.4% vs 91.4%, P =.013). This study shows that impaired mobility is currently the best single predictor for POD and 2-year mortality in high-risk patients undergoing TAVI. Prospective multicenter studies are needed to optimize and to further explore the facilitation of routine use of POD predictors in TAVI pathways of care, and subsequent preventive interventions. Geriatric assessment in the prediction of delirium and long-term survival after transcatheter aortic valve implantation (TAVI). [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: To assess the prevalence of musical hallucinations in patients referred for audiometric testing and to analyze associations with age, sex, degree of hearing loss, asymmetrical hearing loss, and tinnitus. Methods: Patients referred for audiometric testing underwent a semi-structured interview on tinnitus and musical hallucinations. Results: Out of 194 patients, most of whom had mild to moderate hearing loss, seven (3.6%) had musical hallucinations. Significant associations were found with female sex and predominant left-sided hearing impairment, but not with age, severity of hearing loss, or tinnitus. Conclusion: This study offers no evidence that age is a risk factor. Musical hallucinations seem to be prevalent in women with predominant left-sided hearing impairment. [ABSTRACT FROM AUTHOR]

Previous studies have shown that older patients benefited less than younger patients from surgical treatment for colorectal cancer (CRC). However, CRC care has advanced over time, and it is time to assess whether the difference in postoperative mortality between older and younger CRC patients is still present. Patients with primary stage I-III CRC diagnosed between 2005 and 2016 were selected from the Netherlands Cancer Registry (N = 111,778). Trends in postoperative mortality and 1-year postoperative relative survival (RS) were analysed, stratified according to age (<75 versus ≥75 years) and tumour location (colon versus rectum). One-year postoperative RS was analysed to correct for background mortality in the older population. Between 2005 and 2016, 30-day postoperative mortality showed a stronger decrease for older patients (from 10.0% to 4.0% for colon cancer [p < 0.001] and from 8.3% to 2.7% for rectal cancer [p < 0.001]) compared with younger patients (from 2.0% to 0.9% for colon cancer [p < 0.001] and from 1.4% to 0.7% for rectal cancer [p = 0.01]). Between 2005 and 2016, also 1-year RS increased more for older patients (from 84.8% to 94.6% for colon cancer and from 86.1% to 97.2% for rectal cancer) compared with younger patients (from 94.0% to 97.8% for colon cancer and from 96.3% to 98.8% for rectal cancer). Between 2005 and 2016, differences in postoperative mortality between older and younger CRC patients decreased. One-year postoperative RS was almost equal for older and younger patients in 2015–2016. This information is crucial for shared decision-making on surgical treatment. • Differences in mortality between older and younger CRC patients decreased. • One-year relative survival became nearly equal for older and younger patients. • Previous literature is no longer representative of the current clinical practice. [ABSTRACT FROM AUTHOR]

Abstract Respiratory, and cardio-cerebrovascular health-related diseases significantly threaten human health and together with air pollution form a complex pathophysiological system. Other complex biological systems show that increased variance and autocorrelations in time series may act as valid early warning signals for critical transitions. On population level, we determined the likelihood that increased variance and autocorrelation of hospital visit on cardiopulmonary disease preceded critical transitions in population health by human-pollution interactions. We investigated long-term hospital visits from a hospital in Nanjing City, China during 2006–2016 for the most important cardiopulmonary diseases likely to be influenced by air pollution: cerebrovascular accident disease (CVAD), coronary artery disease (CAD), chronic obstructive pulmonary disease (COPD), lung cancer disease (LCD), and the grouped categories of respiratory system disease (RESD) and cardio-cerebrovascular system disease (CCD). The time series of standard deviations (SDs) and autocorrelation at-lag-1 (AR-1) were studied as potential Early-Warning Indicators (EWIs) of transitions in population health. Elevated SDs provided an early warning for critical transitions in visit for LCD and overall CCD and CVAD, for the period of 2012–2013, after which a real transition of increased visit occurred for these disease categories. Statistical testing showed that these SDs were significantly increased (p < 0.1). The long-term air pollution together with intermittent pollution episodes may have triggered critical transitions in population health for cardiopulmonary disease. It is recommended to consider significant increases in variability in time series of relevant system parameters, such as visit, as early warning signs for future transitions in populations' health states. Graphical abstract Unlabelled Image Highlights • The human-pollution interaction can be considered as a complex nonlinear system. • The likelihood of loss of resilience of cardiopulmonary health was investigated. • Elevated standard deviation provides an early warning for critical transitions. • Air pollution may play a pivotal role for transitions in population health. [ABSTRACT FROM AUTHOR]

Purpose of study The first aim is to evaluate, in a sub-study, the recruitment process of the Senior Step Study, which was an intervention study on the self-management of mobility and fall risk; the second aim is to explore the reasons mentioned by older people, from three different settings, for (not) participating. Methods Subjects were community-dwelling older persons, residents of homes for the elderly, and older persons regularly visiting community centres. The effectiveness of different recruitment procedures was analysed for each setting separately. We also analysed reasons for accepting and declining participation between the settings. Results The total inclusion rate was 27.9%. A personal initial approach (i.e., first contact was face-to-face or in a group meeting) did not improve the inclusion rate. More subjects consented to participate after an introductory meeting (which was planned after the first face-to-face contact) compared to persons not having one (p < 0.01). At different settings, subjects gave different reasons for participation. No differences were found in the reasons for refusing participation. Especially in homes for the elderly, people refused to participate because the research was too burdensome. Conclusions The inclusion rates in this study are comparable to other self-management studies with older people. An introductory meeting during which the study design and benefits of participating are explained and formal interim evaluations of the recruitment process may benefit recruitment. Recruiting older persons for self-management tasks is possible with the appropriate recruitment process, enabling more research on this increasingly important research topic. [ABSTRACT FROM AUTHOR]

Background: Research on new treatments for dementia is gaining pace worldwide in an effort to alleviate this growing health care problem. The optimal evaluation of such interventions, however, calls for a practical and credible patient-reported outcome measure.Objectives: To describe the refinement of the Dementia Quality-of-life Instrument (DQI) and present its revised version.Methods: A prototype of the DQI was adapted to cover a broader range of health-related quality of life (HRQOL) and to improve consistency in the descriptions of its domains. A valuation study was then conducted to assign meaningful numbers to all DQI health states. Pairs of DQI states were presented to a sample of professionals working with people with dementia and a representative sample of the Dutch population. They had to repeatedly select the best DQI state, and their responses were statistically modeled to obtain values for each health state.Results: In total, 207 professionals working with people with dementia and 631 members of the general population completed the paired comparison tasks. Statistically significant differences between the two samples were found for the domains of social functioning, mood, and memory. Severe problems with physical health and severe memory problems were deemed most important by the general population. In contrast, severe mood problems were considered most important by professionals working with people with dementia.Discussion: The DQI is a simple and feasible measurement instrument that expresses the overall HRQOL of people suffering from dementia in a single meaningful number. Current results suggest that revisiting the discussion of using values from the general population might be warranted in the dementia context. [ABSTRACT FROM AUTHOR]

Abstract: Comprehensive geriatric assessment (CGA) is a process that consists of a multidimensional data-search and a process of analyzing and linking patient characteristics creating an individualized intervention-plan, carried out by a multidisciplinary team. In general, the positive health care effects of CGA are established, but in oncology both CGA and the presence of geriatric syndromes still have to be implemented to tailor oncological therapies to the needs of elderly cancer patients. In this paper the conceptualization of geriatric syndromes, their relationship to CGA and results of clinical studies using CGA in oncology are summarized. Geriatric syndromes are associated with increased vulnerability and refer to highly prevalent, mostly single symptom states (falls, incontinence, cognitive impairment, dizziness, immobility or syncope). Multifactorial analysis is common in geriatric syndromes and forms part of the theoretical foundation for using CGA. In oncology patients, we reviewed the value of CGA on the following endpoints: recognition of health problems, tolerance to chemotherapy and survival. Most studies performed CGA to identify prognostic factors and did not include an intervention. The ability of CGA to detect relevant health problems in an elderly population is reported consistently but no randomized studies are available. CGA should explore the pre-treatment presence of (in)dependence in Instrumental Activities of Daily Living (IADL), poor or moderately poor quality of life, depressive symptoms and cognitive decline, and thereby may help to predict survival. However, if scored by the Charlson comorbidity-index, comorbidities are not convincingly related to survival. The few studies that included a CGA-linked intervention show inconsistent results with regard to survival but compared to usual care quality of life is improved in the surviving period. Functional performance scores and dependency at home appeared to be independent predictive factors for toxicity, similar to depressive symptoms and polypharmacy. Overall, CGA implements/collects information additional to chronological age and Performance Score. So far in oncology there are no prognostic validation studies reported using geriatric syndromes or information based on CGA in its decision making strategies. [Copyright &y& Elsevier]

• Polygenic risk score-based screen for identifying shared genetic etiology. • There is genetic sharing between Alzheimer's disease and lipid levels in the blood. • Genetic concordance implies higher levels of specific lipids in Alzheimer's disease. • These results may be leveraged to develop novel therapeutic interventions. Late-onset Alzheimer's disease (AD) has a significant genetic component, but the molecular mechanisms through which genetic risk factors contribute to AD pathogenesis are unclear. We screened for genetic sharing between AD and the blood levels of 615 metabolites to elucidate how the polygenic architecture of AD affects metabolomic profiles. We retrieved summary statistics from genome-wide association studies of AD and the metabolite blood levels and assessed for shared genetic etiology, using a polygenic risk score-based approach. For the blood levels of 31 metabolites, all of which were lipids, we identified and replicated genetic sharing with AD. We also found a positive genetic concordance - implying that genetic risk factors for AD are associated with higher blood levels - for 16 of the 31 replicated metabolites. In the brain, lipids and their intermediate metabolites have essential structural and functional roles, such as forming and dynamically regulating synaptic membranes. Our results imply that genetic risk factors for AD affect lipid levels, which may be leveraged to develop novel treatment strategies for AD. [ABSTRACT FROM AUTHOR]

Abstract: Reports on the value of cerebrospinal fluid (CSF) α-synuclein as a biomarker for dementia with Lewy bodies and Parkinson disease are contradicting. This may be explained by fluctuating CSF α-synuclein concentrations over time. Such fluctuations have been suggested for CSF amyloid β concentrations. Furthermore, a physiological relationship between α-synuclein and amyloid β has been suggested based on in vitro research. We performed repeated CSF sampling in healthy elderly and AD patients and showed that sinusoidal fluctuations in CSF α-synuclein concentrations were not present. Furthermore, we did not find evidence for an interaction between amyloid β and α-synuclein concentrations in CSF. [Copyright &y& Elsevier]

Previous studies have shown large heterogeneity in the progression of dementia, both within and between patients. This heterogeneity offers an opportunity to limit the global and individual burden of dementia through the identification of factors associated with slow disease progression in dementia. We explored the heterogeneity in dementia progression to detect disease, patient, and social context factors related to slow progression. Two longitudinal population-based cohort studies with follow-up across 12 years. 512 people with incident dementia from Stockholm (Sweden) contributed to the Kungsholmen Project and the Swedish National Study of Aging and Care in Kungsholmen. We measured cognition using the Mini-Mental State Examination and daily functioning using the Katz Activities of Daily Living Scale. Latent classes of trajectories were identified using a bivariate growth mixture model. We then used bias-corrected logistic regression to identify predictors of slower progression. Two distinct groups of progression were identified; 76% (n = 394) of the people with dementia exhibited relatively slow progression on both cognition and daily functioning, whereas 24% (n = 118) demonstrated more rapid worsening on both outcomes. Predictors of slower disease progression were Alzheimer's disease (AD) dementia type [odds ratio (OR) 2.07, 95% confidence interval (CI) 1.15-3.71], lower age (OR 0.88, 95% CI 0.83-0.94), fewer comorbidities (OR 0.77, 95% CI 0.66-0.90), and a stronger social network (OR 1.72, 95% CI 1.01-2.93). Lower age, AD dementia type, fewer comorbidities, and a good social network appear to be associated with slow cognitive and functional decline. These factors may help to improve the counseling of patients and caregivers and to optimize the planning of care in dementia. [ABSTRACT FROM AUTHOR]

Background: The Older Persons and Informal Caregivers Minimum Data Set (TOPICS-MDS) is a standardized data set that was developed to evaluate the quality of multidimensional geriatric care. There is an inherent need to reduce the number of TOPICS-MDS survey items to core outcomes to allow it to be more easily applied as a patient-reported outcome measure in clinical settings.Objectives: To create a TOPICS-short form (TOPICS-SF) and examine its validity.Methods: Data in the TOPICS-MDS from persons aged 65 years and older in the Netherlands were used for the following analyses. Multiple linear regression analyses were performed to select the items and to derive domain weights of TOPICS-SF. A priori hypotheses were made on the basis of psychometric properties of the full-length TOPICS-MDS preference-weighted score (TOPICS-CEP). The validity of TOPICS-SF was evaluated by 1) examining the meta-correlation of the TOPICS-SF score with TOPICS-CEP and two quality-of-life measures, that is, the Cantril Ladder score and the EuroQol five-dimensional questionnaire utility index, and 2) performing mixed multiple regression of TOPICS-SF scores across key sociodemographic characteristics.Results: TOPICS-SF scores were strongly correlated with the TOPICS-CEP (r = 0.96) and had stronger correlation with the EuroQol five-dimensional questionnaire utility index compared with the Cantril Ladder (r = 0.61 and 0.38, respectively). TOPICS-SF scores were higher among older persons who were married, living independently, and having higher levels of education.Conclusions: We have developed the 22-item TOPICS-SF and demonstrated its validity, supporting its use as a patient-reported outcome measure in geriatric care. [ABSTRACT FROM AUTHOR]

Objectives Understanding which persons most likely use particular combinations of service types is important as this could lead to a better understanding of care pathways. The aim of this study is to identify combinations of service use within a sample of community-dwelling people with mild cognitive impairment (MCI) and dementia and identify factors related to these service use combinations. Methods A latent class analysis performed at baseline on a merged dataset (n = 530) was used to classify care recipients based on following service use types: general practitioner visits, physiotherapist visits, hospital outpatient specialist visits, emergency room visits, hospital inpatient visits with stay over, day care visits, use of domestic homecare, use of personal homecare, and informal care on (instrumental) activities of daily living. Multinomial logistic regression was performed to identify factors associated with service use combinations using clinical characteristics of the care recipient and demographic characteristics of the care recipient and caregiver. Results Three service use classes were identified; a formal homecare class (10% of participants), an informal care class (46% of participants), and a low user class (44% of participants). Factors increasing the likelihood of being in the formal homecare class compared with the low service use class included a diagnosis of MCI or dementia, activities of daily living impairment, older age of the care recipient, and care recipient not living together with the caregiver. Conclusions Besides a diagnosis of MCI or dementia, other factors (activities of daily living impairment, age, and living situation) were associated with service use. We recommend using these factors alongside the diagnostic label for care indication. [ABSTRACT FROM AUTHOR]

Objective: Shared decision-making (SDM) is widely recommended as a way to support patients in making healthcare choices. Due to an ageing population, the number of older patients will increase. Existing models for SDM are not sufficient for this patient group, due to their multi-morbidity, the lack of guidelines and evidence applicable to the numerous combinations of diseases. The aim of this study was to gain consensus on a model for SDM in frail older patients with multiple morbidities.Methods: We used a three-round Delphi study to reach consensus on a model for SDM in older patients with multiple morbidities. The expert panel consisted of 16 patients (round 1), and 59 professionals (rounds 1-3). In round 1, the SDM model was introduced, rounds 2 and 3 were used to validate the importance and feasibility of the SDM model.Results: Consensus for the proposed SDM model as a whole was achieved for both importance (91% panel agreement) and feasibility (76% panel agreement).Conclusions: SDM in older patients with multiple morbidities is a dynamic process. It requires a continuous counselling dialogue between professional and patient or proxy decision maker.Practice Implications: The developed model for SDM in clinical practice may help professionals to apply SDM in the complex situation of the care for older patients. [ABSTRACT FROM AUTHOR]

Sedentary behaviour may increase the risk of dementia. Studying physiological effects of sedentary behaviour on cerebral health may provide new insights into the nature of this association. Accordingly, we reviewed if and how acute and habitual sedentary behaviour relate to brain health factors in middle-aged and older adults (≥45 years). Four databases were searched. Twenty-nine studies were included, with mainly cross-sectional designs. Nine studies examined neurotrophic factors and six studied functional brain measures, with the majority of these studies finding no associations with sedentary behaviour. The results from studies on sedentary behaviour and cerebrovascular measures were inconclusive. There was a tentative association between habitual sedentary behaviour and structural white matter health. An explanatory pathway for this effect might relate to the immediate vascular effects of sitting, such as elevation of blood pressure. Nevertheless, due to the foremost cross-sectional nature of the available evidence, reverse causality could also be a possible explanation. More prospective studies are needed to understand the potential of sedentary behaviour as a target for brain health. • Sedentary behaviour is not associated with neurotrophic factors. • During prolonged sitting acute changes are seen on cerebrovascular measures. • Sedentary behaviour seems particularly associated with reduced white matter health. [ABSTRACT FROM AUTHOR]

BACKGROUND: The objective of this study was to evaluate implementation of an innovative intervention designed to prevent complications and stimulate early rehabilitation among frail elderly inpatients. METHODS: The program was implemented in April 2011. A mixed-methods process evaluation and before-after study were performed. Primary effect outcomes included incidence of hospital-acquired delirium, cognitive decline, and decline in activities of daily living (ADL) during hospital stay. Secondary endpoints included ADL performance 3 months postdischarge, readmission, and caregiver burden RESULTS: One hundred ninety-one preintervention and 195 postintervention patients aged 70 years or older were included. Overall, no significant differences in primary endpoints were found. Mean ADL between discharge and follow-up improved (3.2 vs 5.7, P = .058). Caregivers rated burden of care lower at 3 months postdischarge (.5 vs -- .6, P = .049 RESULTS: One hundred ninety-one preintervention and 195 postintervention patients aged 70 years or older were included. Overall, no significant differences in primary endpoints were found. Mean ADL between discharge and follow-up improved (3.2 vs 5.7, P = .058). Caregivers rated burden of care lower at 3 months postdischarge (.5 vs -- .6, P = .049 CONCLUSIONS: The CareWell in Hospital program was implemented satisfactorily. Although the low baseline delirium incidence (11%), higher comorbidity, and an increasing learning curve during a restricted implementation period potentially influenced the overall effects, this integrated care program may have beneficial effects on outcomes among frail elderly surgical patients. [ABSTRACT FROM AUTHOR]

There is a great concern about the safety of THC-based drugs in older people (≥65 years), as most of THC-trials did not include such group. In this phase 1, randomized, double-blind, double-dummy, placebo-controlled, cross-over trial, we evaluated the safety and pharmacokinetics of three oral doses of Namisol®, a novel THC in tablet form, in older subjects. Twelve healthy older subjects (6 male; mean age 72±5 years) randomly received a single oral dose of 3 mg, 5 mg, or 6.5 mg of THC or matching placebo, in a crossover manner, on each intervention day. The data for 11 subjects were included in the analysis. The data of 1 subject were excluded due to non-compliance to study medication. THC was safe and well tolerated. The most frequently reported adverse events (AEs) were drowsiness (27%) and dry mouth (11%). Subjects reported more AEs with THC 6.5 mg than with 3 mg (p=0.048), 5 mg (p=0.034) and placebo (p=0.013). There was a wide inter-individual variability in plasma concentrations of THC. Subjects for whom the Cmax fell within the sampling period (over 2 h), Cmax was 1.42-4.57 ng/mL and Tmax was 67-92 min. The AUC0-2 h (n=11) was 1.67-3.51 ng/mL. Overall, the pharmacodynamic effects of THC were smaller than effects previously reported in young adults. In conclusion, THC appeared to be safe and well tolerated by healthy older individuals. Data on safety and effectiveness of THC in frail older persons are urgently required, as this population could benefit from the therapeutic applications of THC. [ABSTRACT FROM AUTHOR]

Objectives: To study the reliability and construct validity of the EASY-Care Two-step Older persons Screening (EASY-Care TOS), a practice-based tool that helps family physicians (FPs) to identify their frail older patients. Study Design and Setting: This validation study was conducted in six FP practices. We determined the construct validity by comparing the results of the EASY-Care TOS with other commonly used frailty constructs [Fried Frailty Criteria (FFC), Frailty Index (FI)] and with other related constructs (ie, multimorbidity, disability, cognition, mobility, mental well-being, and social context). To determine interrater reliability, an independent second EASY-Care TOS assessment was made for a subpopulation. Results: We included 587 older patients (mean age 77 ± 5 years, 56% women). According to EASY-Care TOS, 39.4% of patients were frail. EASY-Care TOS frailty correlated better with FI frailty (0.63) than with FFC frailty (0.52). A high correlation was found with multimorbidity (0.50), disabilities (0.53), and mobility (0.55) and a moderate correlation with cognition (0.31) and mental well-being (0.38). Reliability testing showed 89% agreement (Cohen's κ 0.63) between EASY-Care TOS frailty judgment by two different assessments. Conclusion: EASY-Care TOS correlated well with relevant physical and psychosocial measures. Accordingly, these results show that the EASY-Care TOS identifies patients who have a wide spectrum of interacting problems. [ABSTRACT FROM AUTHOR]

Abstract: In Alzheimer''s disease (AD) cerebrovascular function is at risk. Transcranial Doppler, near-infrared spectroscopy, and photoplethysmography are noninvasive methods to continuously measure changes in cerebral blood flow velocity (CBFV), cerebral cortical oxygenated hemoglobin (O2Hb), and blood pressure (BP). In 21 patients with mild to moderate AD and 20 age-matched controls, we investigated how oscillations in cerebral blood flow velocity (CBFV) and O2Hb are associated with spontaneous and induced oscillations in blood pressure (BP) at the very low (VLF = 0.05 Hz) and low frequencies (LF = 0.1 Hz). We applied spectral and transfer function analysis to quantify dynamic cerebral autoregulation and brain tissue oxygenation. In AD, cerebrovascular resistance was substantially higher (34%, AD vs. control: Δ = 0.69 (0.25) mm Hg/cm/second, p = 0.012) and the transmission of very low frequency (VLF) cerebral blood flow (CBF) oscillations into O2Hb differed, with increased phase lag and gain (Δ phase 0.32 [0.15] rad; Δ gain 0.049 [0.014] μmol/cm/second, p both < 0.05). The altered transfer of CBF to cortical oxygenation in AD indicates that properties of the cerebral microvasculature are changed in this disease. [Copyright &y& Elsevier]

Abstract: Background: Conventional techniques to measure health-related quality of life (HRQoL) in a single value or index are complex, require abstract reasoning skills, and are prone to biases (e.g., adaptation). A possible alternative that requires less cognitive demand is Thurstone scaling. The present explorative study investigates the feasibility and concurrent validity of using Thurstone scaling to elicit health-state values in patients with dementia and their proxies. Methods: The participants in the present study were 145 pairs, consisting of community-dwelling persons with dementia and their proxies. We administered the prototype of the dementia quality-of-life instrument (DQI), a dementia-specific HRQoL index instrument, to both patients and proxies. The patient''s health state as defined by the DQI was placed randomly among nine other DQI health states and these were ranked from best to worst. These rankings were used for Thurstone scaling. After ranking, the health states were placed on a visual analogue scale (VAS). Results: Thurstone scaling had a completion rate of 37% for patients and 88% for proxies. Thurstone scaling showed a high correspondence with VAS values. In addition, we identified a trend that shows that patients value most of the evaluated health states systematically lower than proxies. Conclusions: Thurstone scaling proved to be unfeasible for most patients, but feasible for proxies. Its concurrent validity was supported and new insights into patient–proxy discrepancies were discovered. [Copyright &y& Elsevier]

Abstract: Objective: In some trials, the intervention is delivered to individuals in groups, for example, groups that exercise together. The group structure of such trials has to be taken into consideration in the analysis and has an impact on the power of the trial. Our aim was to provide optimal methods for the design and analysis of such trials. Study Design and Setting: We described various treatment allocation methods and presented a new allocation algorithm: optimal batchwise minimization (OBM). We carried out a simulation study to evaluate the performance of unrestricted randomization, stratification, permuted block randomization, deterministic minimization, and OBM. Furthermore, we described appropriate analysis methods and derived a formula to calculate the study size. Results: Stratification, deterministic minimization, and OBM had considerably less risk of imbalance than unrestricted randomization and permuted block randomization. Furthermore, OBM led to unpredictable treatment allocation. The sample size calculation and the analysis of the study must be based on a multilevel model that takes the group structure of the trial into account. Conclusion: Trials evaluating interventions that are carried out in subsequent groups require adapted treatment allocation, power calculation, and analysis methods. From the perspective of obtaining overall balance, we conclude that minimization is the method of choice. When the number of prognostic factors is low, stratification is an excellent alternative. OBM leads to better balance within the batches, but it is more complicated. It is probably most worthwhile in trials with many prognostic factors. From the perspective of predictability, a treatment allocation method, such as OBM, that allocates several subjects at the same time, is superior to other methods because it leads to the lowest possible predictability. [Copyright &y& Elsevier]

Objective: To assess whether a multifactorial fall prevention program was more effective than usual geriatric care in preventing falls and reducing fear of falling in frail community-dwelling older fallers, with and without cognitive impairment, and in alleviating subjective caregiver burden in caregivers. Design, Setting, and Participants: A randomized, 2 parallel-group, single-blind, multicenter trial conducted in 36 pairs of frail fallers, who were referred to a geriatric outpatient clinic after at least 1 fall in the past 6 months, and their informal caregivers. Intervention: Groups of 5 pairs of patients and caregivers received 10 twice-weekly, 2-hour sessions with physical and psychological components and a booster session. Measurements: The primary outcome was the fall rate during a 6-month follow-up. Additionally, we measured fear of falling and subjective caregiver burden. Data on the secondary outcome measures were collected at baseline, directly after, and at 3 and 6 months after the last session of the intervention. Results: Directly after the intervention and at the long-term evaluation, the rate of falls in the intervention group was higher than in the control group, although these differences were not statistically significant (RR = 7.97, P = .07 and RR = 2.12, P = .25, respectively). Fear of falling was higher in the intervention group, and subjective caregiver burden did not differ between groups. Conclusion: Although we meticulously developed this pairwise multifactorial fall prevention program, it was not effective in reducing the fall rate or fear of falling and was not feasible for caregivers, as compared with regular geriatric care. Future research initiatives should be aimed at how to implement the evidence-based principles of geriatric fall prevention for all frail fallers rather than developing more complex interventions for the frailest. [Copyright &y& Elsevier]

Complex interventions are difficult to develop, document, evaluate, and reproduce. Process evaluations aid the interpretation of outcome results by documenting and evaluating each process step in detail. Despite its importance, process evaluations are not embedded in all evaluations of complex interventions. Based on literature, we structured the process evaluation for trials on complex interventions into 3 main components: (1) the success rate of recruitment and quality of the study population, (2) the quality of execution of the complex intervention, and (3) the process of acquisition of the evaluation data. To clarify these process evaluation components and measures, we exemplified them with the preplanned process evaluation of a complex falls-prevention program for community-dwelling frail older fallers and their informal caregivers. The 3 process evaluation components are operationalized, results are presented, and implications discussed. This process evaluation identified several limitations of the intervention and effect study, and resulted in multiple recommendations for improvement of both the intervention as well as the trial. Thus, a good-quality process evaluation gives a detailed description of the most important components of a complex intervention, resulting in an in-depth insight in the actually performed intervention and effect analysis. This allows us to draw the appropriate conclusions on positive or negative trial results, and results in recommendations for implementation, or adjustment of the intervention or effect evaluation, respectively. [Copyright &y& Elsevier]

Abstract: Objectives: In randomized controlled trials with many potential prognostic factors, serious imbalance among treatment groups regarding these factors can occur. Minimization methods can improve balance but increase the possibility of selection bias. We described and evaluated the performance of a new method of treatment allocation, called studywise minimization, that can avoid imbalance by chance and reduce selection bias. Study Design and Setting: The studywise minimization algorithm consists of three steps: (1) calculate the imbalance for all possible allocations, (2) list all allocations with minimum imbalance, and (3) randomly select one of the allocations with minimum imbalance. We carried out a simulation study to compare the performance of studywise minimization with three other allocation methods: randomization, biased-coin minimization, and deterministic minimization. Performance was measured, calculating maximal and average imbalance as a percentage of the group size. Results: Independent of trial size and number of prognostic factors, the risk of serious imbalance was the highest in randomization and absent in studywise minimization. The largest differences among the allocation methods regarding the risk of imbalance were found in small trials. Conclusion: Studywise minimization is particularly useful in small trials, where it eliminates the risk of serious imbalances without generating the occurrence of selection bias. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To estimate clinically relevant changes in functional mobility tests and quantitative gait measures at group and individual level in frail elderly patients. Study Design and Setting: This study was a cohort study of consecutively admitted frail elderly patients. Gait velocity, Timed-Up-and-Go test (TUG), and other mobility tests were measured on admission and 2 weeks later. In between, patients received multidisciplinary treatment. Three experts decided from video recordings if patients had a clinically relevant change in gait, defined as change in the expected risk of falling. Results: A total of 85 patients (mean age 75.8 years, 46 female) participated. Of whom, 45% had dementia; 59 patients were stable and 26 showed a clinically relevant change in gait. Gait velocity and TUG were most sensitive to change at group level. In individual patients, a 5% change from baseline in gait velocity and 9% change in TUG had a sensitivity of 92% and 93% for detection of clinically relevant change, but specificity of 27% and 34%, respectively. Conclusion: At group level, gait velocity and TUG were, from all investigated tests, most sensitive to change and in this perspective the best outcome variables. In individual patients, the high intraindividual variability makes these measures unsuitable as independent screening instruments for clinically relevant changes in gait. [Copyright &y& Elsevier]

The concept of physical resilience may help geriatric medicine objectively assess patients' ability to 'bounce back' from future health challenges. Indicators putatively forecasting resilience have been developed under two paradigms with different perspectives: Critical Slowing Down and Loss of Complexity. This study explored whether these indicators validly reflect the construct of resilience in geriatric inpatients. Geriatric patients (n = 121, 60% female) had their heart rate and physical activity continuously monitored using a chest-worn sensor. Indicators from both paradigms were extracted from both physiological signals. Measures of health functioning, concomitant with low resilience, were obtained by questionnaire at admission. The relationships among indicators and their associations with health functioning were assessed by correlation and linear regression analyses, respectively. Greater complexity and higher variance in physical activity were associated with lower frailty (β = −0.28, p =.004 and β = −0.37, p <.001, respectively) and better ADL function (β = 0.23, p =.022 and β = 0.38, p <.001). The associations of physical activity variance with health functioning were not in the expected direction based on Critical Slowing Down. In retrospect, these observations stress the importance of matching the resilience paradigm's assumptions to the homeostatic role of the variable monitored. We present several lessons learned. • Quantifying physical resilience may help assess recovery potential in the elderly. • Complexity Science offers quantitative indicators to capture aspects of resilience. • Critical Slowing Down and Loss of Complexity assess different underlying mechanisms. • Physical activity complexity and variance coincided with better health functioning. • The assumptions of the paradigm must match the homeostatic roles of the variables. [ABSTRACT FROM AUTHOR]

Acute illnesses and subsequent hospital admissions present large health stressors to older adults, after which their recovery is variable. The concept of physical resilience offers opportunities to develop dynamical tools to predict an individual's recovery potential. This study aimed to investigate if dynamical resilience indicators based on repeated physical and mental measurements in acutely hospitalized geriatric patients have added value over single baseline measurements in predicting favorable recovery. Intensive longitudinal study. 121 patients (aged 84.3 ± 6.2 years, 60% female) admitted to the geriatric ward for acute illness. In addition to preadmission characteristics (frailty, multimorbidity), in-hospital heart rate and physical activity were continuously monitored with a wearable sensor. Momentary well-being (life satisfaction, anxiety, discomfort) was measured by experience sampling 4 times per day. The added value of dynamical indicators of resilience was investigated for predicting recovery at hospital discharge and 3 months later. 31% of participants satisfied the criteria of good recovery at hospital discharge and 50% after 3 months. A combination of a frailty index, multimorbidity, Clinical Frailty Scale, and or gait speed predicted good recovery reasonably well on the short term [area under the receiver operating characteristic curve (AUC) = 0.79], but only moderately after 3 months (AUC = 0.70). On addition of dynamical resilience indicators, the AUC for predicting good 3-month recovery increased to 0.79 (P =.03). Variability in life satisfaction and anxiety during the hospital stay were independent predictors of good 3-month recovery [odds ratio (OR) = 0.24, P =.01, and OR = 0.54, P =.04, respectively]. These results highlight that measurements capturing the dynamic functioning of multiple physiological systems have added value in assessing physical resilience in clinical practice, especially those monitoring mental responses. Improved monitoring and prediction of physical resilience could help target intensive treatment options and subsequent geriatric rehabilitation to patients who will most likely benefit from them. [ABSTRACT FROM AUTHOR]

People with dementia are known to be physically frailer, more sedentary, and participate less in regular physical exercise compared to their healthy peers. Physical activity interventions have the potential to reduce the level of frailty in community-dwelling older adults. Exergaming combines physical exercise with cognitive stimulation in a virtual environment. It is an innovative and fun way of exercising, which may aid people with dementia to be more physically active. The primary aim of this study was to investigate the efficacy of a 12-week exergame training and equally long aerobic training, both compared to an active control group, on frailty in people with dementia. A 3-armed randomized controlled trial compared exergame training, aerobic training, and an active control intervention. 115 people with dementia [mean (standard deviation [SD]) age = 79.2 (6.9) years; mean (SD) Mini-Mental State Examination score = 22.9 (3.4)]. Participants were randomized and individually trained 3 times a week during 12 weeks. The Evaluative Frailty Index for Physical activity (EFIP) was used to assess the level of frailty at baseline and after the 12-week intervention period. Between-group differences were analyzed with analysis of covariance. The exergame group showed a trend toward higher adherence compared to the aerobic group (87.3% vs 81.1%, P =.05). A significant reduction on the EFIP was found in the exergame group (EG) compared to the active control group (CG) [mean difference (95% confidence interval) between EG and CG: −0.034 [–0.062, −0.007], P =.012], with a small-to-moderate effect size (partial η2 = 0.055). This is the first study to show that a 12-week exergame intervention reduces the level of frailty in people with dementia. This is an important and promising result, because frailty is a powerful predictor for adverse health outcomes, and its reduction may have positive effects on health status. Moreover, exergaming resulted in high adherence rates of physical exercise, which makes it an effective strategy to engage people with dementia in physical activity. [ABSTRACT FROM AUTHOR]

Abstract Objectives The predictive value of frailty and comorbidity, in addition to more readily available information, is not widely studied. We determined the incremental predictive value of frailty and comorbidity for mortality and institutionalization across both short and long prediction periods in persons with dementia. Design Longitudinal clinical cohort study with a follow-up of institutionalization and mortality occurrence across 7 years after baseline. Setting and Participants 331 newly diagnosed dementia patients, originating from 3 Alzheimer centers (Amsterdam, Maastricht, and Nijmegen) in the Netherlands, contributed to the Clinical Course of Cognition and Comorbidity (4C) Study. Measures We measured comorbidity burden using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G) and constructed a Frailty Index (FI) based on 35 items. Time-to-death and time-to-institutionalization from dementia diagnosis onward were verified through linkage to the Dutch population registry. Results After 7 years, 131 patients were institutionalized and 160 patients had died. Compared with a previously developed prediction model for survival in dementia, our Cox regression model showed a significant improvement in model concordance (U) after the addition of baseline CIRS-G or FI when examining mortality across 3 years (FI: U = 0.178, P =.005, CIRS-G: U = 0.180, P =.012), but not for mortality across 6 years (FI: U = 0.068, P =.176, CIRS-G: U = 0.084, P =.119). In a competing risk regression model for time-to-institutionalization, baseline CIRS-G and FI did not improve the prediction across any of the periods. Conclusions Characteristics such as frailty and comorbidity change over time and therefore their predictive value is likely maximized in the short term. These results call for a shift in our approach to prognostic modeling for chronic diseases, focusing on yearly predictions rather than a single prediction across multiple years. Our findings underline the importance of considering possible fluctuations in predictors over time by performing regular longitudinal assessments in future studies as well as in clinical practice. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The primary objective of this study was to systematically examine the physical functioning of older persons with somatoform disorders, as this has never been carried out before. Second, we wanted to test our hypothesis that higher somatic disease burden in patients with somatoform disorders is associated with a higher level of somatisation. Design and Setting: Observational study of patients referred for medically unexplained symptoms (MUS) to our outpatient mental health center for older adults. The patients were offered a standardized, multidisciplinary diagnostic procedure, including a comprehensive geriatric assessment. Inter-rater reliability between two geriatricians assessing the contribution of somatic pathology to the main somatic symptom was assessed. Participants: A total of 37 patients referred for MUS (mean age 75 ± 6 years). Measurements: Timed up and go test (TUG) and hand grip strength were used as measures for frailty; the Cumulative Index Rating Scale for Geriatrics (CIRS-G) sum score and severity index measured the burden of cumulative somatic morbidity. The Groningen Activity Rating Scale (GARS) measured functional status. The Whitely Index was used as measure for somatisation. Results: Patients’ main symptom could be completely explained by a somatic disease in 3/37 (8%) patients (kappa between geriatricians = 0.72). A total of 32 patients met the criterion for a Somatoform Disorder according to DSM-IV-TR criteria, but somatic comorbidity partially explained the main symptom in 15/32 patients. These patients were older (P = .049), had more somatic comorbidity (P = .049), a slower gait speed (TUG, P = .035), a lower hand grip strength (P = .050), and a lower functional status (P = .30) compared with the 17 patients without any explanation for their main somatic symptom. In contrast to our hypothesis, a higher level of somatisation was associated with less somatic disease burden. Conclusion: Geriatric assessment has an important added value in older patients referred with medically unexplained symptoms because in half of these patients, symptoms can be partially or fully explicable following careful assessment of comorbidity and frailty. [Copyright &y& Elsevier]

Abstract: Large hour-to-hour variability has previously been demonstrated in the cerebrospinal fluid (CSF) concentrations of Alzheimer''s disease (AD) biomarkers amyloid β42 (Aβ42) and Aβ40 in healthy younger subjects. We investigated the within-subject variability over 36 hours in CSF Aβ and tau proteins, in older subjects and AD patients. Six patients with mild stage AD (59–85 years, Mini Mental State Examination (MMSE) 16–26) and 6 healthy older volunteers (64–77 years) received an intrathecal catheter from which, during 36 hours, each hour 6 mL of CSF was drawn. Concentrations of Aβ42, Aβ40, total tau, and phosphorylated tau were determined and the variability was analyzed. Within-subject variability within 3-hour periods was assessed as the coefficient of variation, which was comparable for these 4 biomarkers in controls (4.2%–4.6%) and AD (3.1%–5.8%). Variability over 12 hour periods was 5.3% to 9.5%. These findings suggest that CSF biomarker variability is relatively low in healthy older controls and AD patients. Furthermore, continuous sampling of CSF proved to be a useful and robust method, which may also be used to investigate AD pathogenesis and to evaluate pharmacotherapeutic interventions. [Copyright &y& Elsevier]

Abstract: Objectives: The authors’ first aim was to study the effects of raloxifene and tibolone on body mass density, handgrip strength, and other secondary frailty components. The secondary aim was to compare the effects of raloxifene and tibolone and their safety in older women. Design/Setting/Participants: A randomized, double-blind, double- dummy, placebo-controlled trial conducted in an academic hospital in the Netherlands among 318 community living women aged >70 were randomized; 290 received the allocated intervention: 97 placebo, 101 raloxifene, and 92 tibolone. Interventions: Randomization was made to raloxifene 60 mg, tibolone 1.25 mg, or placebo. Assessments were performed at baseline and after 3, 6, 12, and 24 months. The study was conducted from July 2003 to January 2008. The tibolone group stopped earlier in February 2006, because of results of the Long-Term Intervention on Fractures with Tibolone study, suggesting an increased risk of cerebrovascular accident. Measurements: Primary endpoints were body mass density and handgrip strength. Secondary endpoints were muscle power and strength, mobility measures, body composition, verbal memory, mental processing speed, anxiety, mood, and quality of life. Results: Tibolone and raloxifene had similar body mass density-effect sizes (d = .24–.47), and had no effect on handgrip muscle strength. For the 15 words test the effect on direct recall of concrete and abstract words (d = .40 and d =.27, respectively) and on delayed recall of concrete words (d = .77) were significantly higher in the raloxifene group compared to placebo and to tibolone. In the raloxifene group the health status (EuroQol VAS (0–100) was improved 2.4 points [95% CI 0.5–4.2; P = .012] over 24 months. Conclusion: In women >70 years old, raloxifene and tibolone significantly and similarly increased body mass density but not muscle strength. Raloxifene had also positive effects on verbal memory and health status. New research with selective estrogen receptor modulators like raloxifene might be promising on frailty endpoints in elderly women. Trial registration number: Nederlands Trial Register: 1232 [Copyright &y& Elsevier]