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Insight into older adults' physical resilience is needed to predict functional recovery after hospitalization. We assessed functional trajectories in response to acute illness and subsequent hospitalization and investigated baseline variables and dynamic variables associated with these trajectories. Prospective observational cohort study (Hospitalization-Associated Disability and impact on daily Life Study). This study included 207 older adults (aged 79.8 ± 6.9 years, 49% female, 57% frail) acutely hospitalized in 6 Dutch hospitals. Functional disability was assessed using the 15-item modified activities of daily living index retrospectively 2 weeks before admission, and prospectively from admission up to 3 months after discharge. Baseline variables including frailty, somatic, physical, and psychosocial factors were assessed at admission. Dynamic variables (step count, pain, fatigue, and fear of falling) were continuously or repeatedly assessed during hospitalization. We performed individual spline modeling using random effects. Baseline variables and within-person mean levels and variability in the dynamic variables were assessed as predictors of functional trajectories. Functional disability significantly increased before admission and decreased from admission to 3 months post discharge. Frail participants had a significantly higher increase in functional disability before admission compared with nonfrail participants. Lower step count, higher pain scores, and higher within-person variability in fear of falling were significantly associated with higher increase in functional disability before admission. Higher within-person variability in fear of falling was associated with more recovery. Older adults increase in functional disability before hospitalization and start to recover from admission onward. Frailty and dynamic variables are associated with a higher increase in functional disability after acute illness. Our findings give more insight into older adults' physical resilience, which may improve the prediction of functional recovery and may improve therapeutic decision-making and rehabilitation strategies to improve functional recovery after acute hospitalization. [ABSTRACT FROM AUTHOR]

Objectives: The Revised Cambridge Cognitive Examination (CAMCOG-R) is a cognitive screen that has been used to discriminate individuals with dementia from cognitively intact older people. It consists of items assessing various cognitive domains, but the construct validity of the cognitive subscores has not been established yet. The authors examine the subscores Memory and Executive Function in relation to extensive neuropsychological testing in a group of older adults with or without cognitive decline. Design: Observational study. Setting: Memory clinic at the department of geriatrics of a university medical center. Participants: A convenience sample of 36 outpatients diagnosed with cognitive decline and 24 older healthy participants. Measurements: Sensitivity and specificity of the CAMCOG-R Memory subscore and Executive Function subscore were established using extensive neuropsychological assessment of memory (using the Rey-Auditory Verbal Learning Test, Location Learning Test, Visual Association Test, and Story Recall) and executive function (using the Brixton Spatial Anticipation Test, Trail Making Test, and Key Search test) as the gold standard. Results: For the CAMCOG-R Executive Function subscore, a cutoff point of 165 had a good sensitivity (0.82) and adequate specificity (0.73) for discriminating people with and without executive dysfunction. However, the Total Score and Language subscore also differentiated between people with and without executive dysfunction. The CAMCOG-R Memory subscore could not validly distinguish between people with and without memory impairment. Conclusion: The CAMCOG-R subscores Memory and Executive Function have limited validity, and clinicians should be cautious in interpreting these in the absence of other neuropsychological measures or clinical information. [ABSTRACT FROM AUTHOR]

Abstract: Objective: In the Dutch EASYcare Study, pseudo cluster randomization (PCR) randomized clinicians in two groups (H and L) with a high or a low proportion of the patients of the clinician randomized to intervention or to control arm accordingly. We used PCR because cluster randomization risked selection bias and individual randomization risked contamination. We evaluated the performance of PCR. Study Design and Setting: Clinicians were asked about treatment arm preferences, recruitment behavior, possible contaminating behavior, and what they thought the allocation ratio was. We compared patients'' baseline characteristics and clinicians'' recruitment rates. Results: The groups were comparable at baseline. Clinicians favored the intervention arm (Visual Analogue Scale 14.5 [SD 15.6]; 0–100; 0=strongly favoring intervention arm, 100=strongly favoring usual care arm) and 58% said they would have recruited fewer patients had every participant been allocated to the control group. Sixty five percent of clinicians used intervention elements in control patients. Sixty seven percent of clinicians estimated that a 50:50 allocation ratio was used. Conclusion: The assumptions underlying PCR largely applied in this study. PCR performed satisfactorily without signs of unblinding or selection bias. [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]

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: A literature search was carried out to summarize the existing scientific evidence concerning occurrence, causes, and consequences of multimorbidity (the coexistence of multiple chronic diseases) in the elderly as well as models and quality of care of persons with multimorbidity. According to pre-established inclusion criteria, and using different search strategies, 41 articles were included (four of these were methodological papers only). Prevalence of multimorbidity in older persons ranges from 55 to 98%. In cross-sectional studies, older age, female gender, and low socioeconomic status are factors associated with multimorbidity, confirmed by longitudinal studies as well. Major consequences of multimorbidity are disability and functional decline, poor quality of life, and high health care costs. Controversial results were found on multimorbidity and mortality risk. Methodological issues in evaluating multimorbidity are discussed as well as future research needs, especially concerning etiological factors, combinations and clustering of chronic diseases, and care models for persons affected by multiple disorders. New insights in this field can lead to the identification of preventive strategies and better treatment of multimorbid patients. [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]

Abstract: We describe a modification of a previously described assay for the quantification of α-synuclein in naive cerebrospinal fluid, which allows for a more efficient quantification of α-synuclein. Detection limit of the assay is 3.8ng/ml and the assay is linear until 300ng/ml. Inter-assay and intra-assay coefficients of variation are below 15% in a wide range of concentrations. Mean recovery of the assay is 94%. The 95% upper limit of the reference range (p95) in a group of neurological controls above the age of 45 years is 62ng/ml. This assay can be routinely applied for quantification of α-synuclein in cerebrospinal fluid, but not in serum, and this may serve as a possible biomarker for α-synucleinopathies such as Parkinson''s disease and multiple system atrophy. [Copyright &y& Elsevier]

• This meta-analysis suggests that people with both cognitive impairment and physical frailty have the highest dementia risk. • These results support the existence of an interplay between physical and cognitive domains in the development of dementia. • The inclusion of a frailty evaluation in the assessment of people with CIND may enable more reliable dementia prediction. • Studies on mechanisms underlying cognitive and physical decline might open new avenues for dementia prevention and treatment. Cognitive impairment and frailty are important health determinants, independently associated with increased dementia risk. In this meta-analysis we aimed to quantify the association of the co-occurrence of cognitive impairment no dementia (CIND) and physical frailty with incident dementia. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used when reporting this review. We performed a systematic search on PubMed, Web of Science, and Embase databases for relevant articles. Longitudinal studies enrolling individuals with both CIND and physical frailty and reporting dementia incidence were eligible. Pooled estimates were obtained through random effect models and Mantel-Haenszel weighting. Out of 3684 articles, five (14302 participants) were included in the meta-analysis. In comparison to participants free from frailty and CIND, the pooled hazard ratio for dementia was 3.83 (95% confidence interval [CI]: 2.64–5.56) for isolated CIND, 1.47 (95%CI: 0.89–2.40) for isolated physical frailty, and 5.36 (95%CI: 3.26–8.81) for their co-occurrence. The co-occurrence of cognitive impairment and physical frailty is a clinical marker of incident dementia. [ABSTRACT FROM AUTHOR]

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]

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]

Objectives With the lack of a cure for Alzheimer disease (AD), the identification of comorbidity is important to reduce the possibility of excess disability. Although comorbidity in patients with late-onset AD (LO-AD) is common, for people with young-onset AD (YO-AD), it is unclear how often comorbidity occurs. Furthermore, it is uncertain whether comorbidity in patients with YO-AD differs from that in patients with LO-AD. The aim of this study was to explore the prevalence, types of morbidity, and morbidity profiles in patients with YO-AD compared with those of patients with LO-AD. Design Explorative cohort study from 2 separate Dutch cohorts (Needs in Young-onset Dementia [NeedYD] and the Clinical Course of Cognition and Comorbidity–Dementia Study [4C-Dementia study]). Setting Participants were recruited in 2007 and 2008 from (1) the memory clinics of 3 Dutch Alzheimer centers, (2) the memory clinics of general hospitals, (3) mental health services in the southern part of the Netherlands, and (4) young-onset dementia specialized day care facilities. A comparison group of community-dwelling, elderly patients with AD was selected from the 4C-Dementia study. Patients in this study were recruited in 2010 and 2011 from the aforementioned Alzheimer centers. Measurements The prevalence rates of comorbidity were compared between 177 patients with YO-AD and 155 patients with LO-AD. Comorbidity was classified using the International Classification of Diseases, 10th Revision (ICD-10). The total amount of comorbidity was established by counting the number of existing diseases (ICD categories or chapters) and comorbidity was also dichotomized as present or absent. Furthermore, a hierarchical cluster analysis was performed to study clusters of comorbidity. Results Compared with LO-AD, patients with YO-AD showed less ( P < .001) overall comorbidity (58.2% vs 86.5%) and had lower prevalence rates of diabetes, obesity, and circulatory diseases; however, the prevalence rates of diseases of the nervous system in YO-AD (6.2%) were higher compared with those of patients with LO-AD (4.5%). The cluster analysis revealed a distinctive group of patients with YO-AD with either no comorbidity or with a disease of the nervous system. Endocrine, nutritional, and metabolic diseases and diseases of the circulatory system were present in 34% of the patients with YO-AD. Conclusion Comorbidity is less common in YO-AD than in LO-AD. However, general practitioners should be aware that approximately one-third of the patients with YO-AD suffer from or have endocrine, nutritional, and metabolic diseases and/or diseases of the circulatory system. Treatment should therefore not only focus on dementia but also on comorbidity. This attention may slow the functional decline in AD. These exploratory analyses suggested a higher prevalence of nervous system diseases in YO-AD compared with LO-AD. However, the finding did not reach statistical significance and in combination with the exploratory nature of the analyses justifies further investigation. If verified, this finding may help to decrease the time to diagnosis of AD and, subsequently, support in young patients with a neurological disease. Further investigation is needed to gain more insight into the association between comorbidity and AD in younger people. [ABSTRACT FROM AUTHOR]

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]

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]