The Measurement of Everyday Cognition (ECog): Revisions and Updates.

INTRODUCTION: The Everyday Cognition scale (ECog), a measure of everyday functioning developed in 2008, is sensitive to early detection and progression of neurodegenerative disease. The goal was to update ECog item content to ensure relevancy to contemporary older adults from diverse backgrounds. METHODS: Participants included 44 culturally diverse older adults (18 with normal cognition, 11 with mild cognitive impairment) and their study partners. Item understandability and relevance was evaluated using iterative interviewing methods that were analyzed using standard qualitative methods. On the basis of this information, items were modified, deleted, or developed as needed. RESULTS: Of the 39 original items, 19 were revised, 3 new items were added (primarily to cover contemporary activities such as the use of technology), and 1 was deleted. The revised version (ECog-II) includes 41 items. DISCUSSION: To ensure strong psychometric properties, and to facilitate harmonization of previously collected data, we preserved well over half of the items. Future work will validate the revised ECog by measuring associations with neuropsychological performance, external measures of disease, and other functional measures. Overall, the revised ECog will continue to be a useful tool for measuring cognitively relevant everyday abilities in clinical settings and intervention clinical trials.

Development of a patient-reported outcome instrument to assess complex activities of daily living and interpersonal functioning in persons with mild cognitive impairment: The qualitative research phase.

INTRODUCTION: As drug development research efforts move toward studying patients earlier in the course of Alzheimer's disease (AD), it is important to incorporate the patient's perspective into measurement of outcomes. METHODS: This article summarizes the qualitative work of the Patient-Reported Outcome Consortium's Cognition Working Group in the development of a new self-reported outcome measure in persons with mild cognitive impairment (MCI) due to suspected AD, herein referred to as MCI. RESULTS: The draft measure captures the patient's voice for two functional domains, complex activities of daily living and interpersonal functioning. DISCUSSION: This work represents a series of initial steps in the development of this rating scale. The next steps are to conduct psychometric analysis and evaluate the role of insight.

Assessing cognition and function in Alzheimer's disease clinical trials: do we have the right tools?

Several lines of evidence from Alzheimer's disease (AD) research continue to support the notion that the biological changes associated with AD are occurring possibly several decades before an individual will experience the cognitive and functional changes associated with the disease. The National Institute on Aging-Alzheimer's Association revised criteria for AD provided a framework for this new thinking. As a result of this growing understanding, several research efforts have launched or will be launching large secondary prevention trials in AD. These and other efforts have clearly demonstrated a need for better measures of cognitive and functional change in people with the earliest changes associated with AD. Recent draft guidance from the US Food and Drug Administration further elevated the importance of cognitive and functional assessments in early stage clinical trials by proposing that even in the pre-symptomatic stages of the disease, approval will be contingent on demonstrating clinical meaningfulness. The Alzheimer's Association's Research Roundtable addressed these issues at its fall meeting October 28-29, 2013, in Washington, D.C. The focus of the discussion included the need for improved cognitive and functional outcome measures for clinical of participants with preclinical AD and those diagnosed with Mild Cognitive Impairment due to AD.

Potential Impact of Slowing Disease Progression in Early Symptomatic Alzheimer's Disease on Patient Quality of Life, Caregiver Time, and Total Societal Costs: Estimates Based on Findings from GERAS-US Study.

Background: Impact of Alzheimer's disease (AD) progression on patient health-related quality of life (HRQoL), caregiver time, and societal costs is not well characterized in early AD. Objective: To assess the association of change in cognition with HRQoL, caregiver time, and societal costs over 36 months, and estimate the impact of slowing disease progression on these outcomes. Methods: This post-hoc analysis included patients with amyloid-positive mild cognitive impairment (MCI) and mild AD dementia (MILD AD) from the 36-month GERAS-US study. Disease progression was assessed using the Mini-Mental State Examination score. Change in outcomes associated with slowing AD progression was estimated using coefficients from generalized linear models. Results: At baseline, 300 patients had MCI and 317 had MILD AD. Observed natural progression over 36 months was associated with: 5.1 point decline in the Bath Assessment of Subjective Quality of Life in Dementia (BASQID) score (for HRQoL), increase in 1,050 hours of total caregiver time, and $8,504 total societal costs for MCI; 6.6 point decline in the BASQID score, increase in 1,929 hours of total caregiver time, and $12,795 total societal costs for MILD AD per person. Slowing AD progression by 30% could result in per person savings in HRQoL decline, total caregiver time, and total societal costs: for MCI: 1.5 points, 315 hours, and $2,638; for MILD AD: 2.0 points, 579 hours, and $3,974. Conclusions: Slowing AD progression over 36 months could slow decline in HRQoL and save caregiver time and societal cost in patients with MCI and MILD AD.

Understanding the impact of slowing disease progression for individuals with biomarker-confirmed early symptomatic Alzheimer's disease.

Recent advances in development of amyloid-targeting therapies support the potential to slow the rate of progression of Alzheimer's disease. We conducted a narrative review of published evidence identified through a targeted search of the MEDLINE and EMBASE databases (2020-2023), recent presentations at disease-specific conferences, and data updates from cohort studies in Alzheimer's disease to describe the trajectory of the progression of Alzheimer's disease. Our findings enable the interpretation of clinical trial results and the value associated with slowing disease progression across outcomes of relevance to patients, care partners, clinicians, researchers and policymakers.Even at the earliest stages, Alzheimer's disease imposes a substantial burden on individuals, care partners, and healthcare systems. The magnitude of the burden increases with the rate of disease progression and symptom severity, as worsening cognitive decline and physical impairment result in loss of functional independence. Data from cohort studies also indicate that slowing disease progression is associated with decreased likelihood of needing extensive clinical care over at least 5 years, decreased care partner burden, and substantial individual and societal cost savings.Slowed disease progression is of significant benefit to individuals with Alzheimer's disease, their loved ones, and the healthcare system. As clinicians and policymakers devise strategies to improve access to treatment earlier in the disease spectrum, they should carefully weigh the benefits of slowing progression early in the disease (e.g. preservation of cognitive and functional abilities, as well as relative independence) to individuals, their loved ones, and broader society.

Clinical and Economic Assessment in Early-Stage Dementia by Severity and Amyloid-ß Status: A 5-Year Retrospective Claims Study of GERAS-US Patients.

BACKGROUND: The high burden of dementia and Alzheimer's disease (AD) increases substantially as disease progresses. Characterizing early patterns of health care utilization among patients who develop cognitive impairment may deepen our understanding of early disease trajectory and potentially facilitate timely diagnosis and management. OBJECTIVE: Describe clinical characteristics, healthcare utilization, and costs in early-stage dementia by disease severity and amyloid-ß status before enrollment in an observational study (GERAS-US). METHODS: Consented patients' GERAS-US data were linked to available five-years of Medicare claims history before GERAS-US enrollment. Clinical characteristics, comorbidity, and pre-/post-diagnosis healthcare use and costs were assessed. Continuous and categorical variables were compared between severity and amyloid-status cohorts using t-test and Chi-square statistics; linear regression models were used to compare cost and utilization measures after adjusting for differences in patients' observation time. Relative likelihood of observed diagnoses, comorbidity, and prescription drug use among cohorts were presented as OR and 90% confidence interval (CI). RESULTS: Of 174 patients clinically diagnosed with early dementia (mild cognitive impairment (MCI): 101; mild dementia (MILD): 73), 55% were amyloid-positive. Memory loss was more likely in MILD versus MCI (OR:1.85, 90% CI 1.10-3.09) and in amyloid-positive versus amyloid-negative cohorts (OR:1.98, 90% CI 1.19-3.29). Mean annual healthcare costs after cognitive impairment/dementia diagnosis were significantly higher for MILD versus MCI ($1191 versus $712, p = 0.067) and amyloid-negative versus amyloid-positive ($1281 versus $701, p = 0.034). Diabetes was more prevalent in MILD and amyloid-negative cohorts. CONCLUSION: Comorbidity and economic burden increased in earliest stages of MCI and MILD and were higher in patients who were amyloid-negative.

Disease progression and costs at the 3-year follow-up of the GERAS-US study.

Introduction: GERAS-US prospectively characterized clinical and economic outcomes of early symptomatic Alzheimer's disease (AD). Societal cost changes were examined in amyloid-positive patients with mild cognitive impairment due to AD (MCI) and mild dementia due to AD (MILD). Methods: Cognition, function, and caregiver burden were assessed using Mini-Mental State Examination (MMSE), Cognitive Function Index (CFI), and Zarit Burden Interview, respectively. Costs are presented as least square mean for the overall population and for MCI versus MILD using mixed model repeated measures. Results: MMSE score and CFI worsened. Total societal costs (dollars/month) for MCI and MILD, respectively, were higher at baseline ($2430 and $4063) but steady from 6 ($1977 and $3032) to 36 months ($2007 and $3392). Direct non-medical costs rose significantly for MILD. Caregiver burden was higher for MILD versus MCI at 12, 18, and 24 months. Discussion: Function and cognition declined in MILD. Non-medical costs reflect the increasing impact of AD even in its early stages. HIGHLIGHTS: In the GERAS-US study, total societal costs for patients with mild cognitive impairment due to Alzheimer's disease (MCI) and mild dementia due to Alzheimer's disease (MILD) were higher at baseline but steady from 6 to 36 months.Mini-Mental State Examination (MMSE) and Cognitive Function Index (CFI) worsened; the rate of decline was significant for patients with MILD but not for those with MCI.There was a rise in direct non-medical costs at 36 months for patients with MILD.Caregiver burden was higher for MILD versus MCI at 12, 18, and 24 months.Slowing the rate of disease progression in this early symptomatic population may allow patients to maintain their ability to carry out everyday activities longer.

Disease Progression and Longitudinal Clinical Outcomes of Lewy Body Dementia in the NACC Database.

INTRODUCTION: As the identification of Lewy body dementia (LBD) is often confirmed postmortem, there is a paucity of evidence on the progression of disease antemortem. This study aimed to comprehensively assess the course of LBD over time across cognitive, functional, and neuropsychiatric outcomes using real-world data. METHODS: Adults with at least one visit to an Alzheimer's Disease Center with a diagnosis of mild cognitive impairment/dementia (index date), indication of LBD, and at least one follow-up visit were identified in the National Alzheimer's Coordinating Center database (September 2005-June 2020). Participant characteristics, medication use, comorbidities, and changes in outcomes were assessed over a 5-year follow-up period and stratified by disease severity based on the Clinical Dementia Rating (CDR®) Dementia Staging Instrument-Sum of Boxes (CDR-SB) score at index. RESULTS: A total of 2052 participants with LBD (mean age at index 73.4 years) were included (mild, 219; moderate, 988; severe, 845). Mean annualized increase over 5 years was 0.9 points for CDR-Global Score, 5.6 points for CDR-SB, 10.4 points for the Functional Activities Questionnaire, and 2.0 points for the Neuropsychiatric Inventory-Questionnaire. Disease progression was greater among participants with moderate and severe LBD at index compared with those with mild LBD. CONCLUSION: Participants with LBD experienced decline across all outcomes over time, and impairment increased with disease severity. Findings highlight the substantial clinical burden associated with LBD and the importance of earlier diagnosis and effective treatment. Further research is needed to understand the predictors of cognitive and functional decline in LBD which may help inform clinical trials.

Thinking about the past, present, and future: Time perspective and self-esteem in adolescents, young adults, middle-aged adults, and older adults.

We examined time perspective and self-esteem in adolescents, young adults, middle-aged adults, and older adults. Time perspective was measured with scales that assess relative orientations and relationships among the past, present, and future. Age effects were examined with standard analytic strategies to determine categorical differences between age groups and with new statistical techniques designed to show continuous age patterns. Findings indicated that (1) thinking about the future was greatest for adolescents and young adults and lowest for middle-aged and older adults, and thinking about the present increased across ages; (2) fewer adolescents and middle-aged participants perceived that the time periods were interrelated compared to younger and older adults; and (3) across ages, a greater emphasis towards the past compared to other time periods was associated with lower self-esteem, whereas emphasizing the present and the future jointly was associated with higher self-esteem.

Demonstration of Clinical Meaningfulness of the Integrated Alzheimer's Disease Rating Scale (iADRS): Association Between Change in iADRS Scores and Patient and Caregiver Health Outcomes.

BACKGROUND: The integrated Alzheimer's Disease Rating Scale (iADRS) is a validated cognitive/functional composite that effectively captures cognitive and functional decline over a broad spectrum of disease. The clinical meaningfulness of change on iADRS can be supported by establishing an association with changes on important health outcome measures. OBJECTIVE: To evaluate the relationship between change on the iADRS and changes in health outcomes in individuals with mild cognitive impairment (MCI) due to Alzheimer's disease (AD), or mild or moderate AD dementia using placebo data from four AD clinical trials and data from one AD observational study. METHODS: Analysis of covariate (ANCOVA) models were used to estimate the relationship between 18-month change on the iADRS and changes on health outcome measures (related to cost, quality of life, and caregiver burden). The regression coefficients for the iADRS were used to compute impact of natural disease progression and disease-modifying treatment on health outcomes. Additional ANCOVAs were conducted to understand whether cognition and/or function was the underlying explanation of any association between iADRS and health outcome change. RESULTS: Across datasets and disease stages, a worsening on the iADRS was significantly associated with increased societal costs, caregiver burden (time and distress) and worsening in measures of patient quality of life. CONCLUSION: Decline on the iADRS was associated with worsening in health outcome measures. These findings suggest that the iADRS can be used in clinical trials as a proxy measure of clinically meaningful outcomes of AD progression.

Epidemiology and economic burden of Lewy body dementia in the United States.

OBJECTIVE: To describe the trends in epidemiology, healthcare resource use (HCRU), and costs associated with Lewy body dementia (LBD), dementia with Lewy bodies (DLB), and Parkinson's disease dementia (PDD) in the United States. METHODS: This retrospective study used administrative claims data for Medicare fee-for-service (2010-2018) and commercially-insured beneficiaries (2010-2017). The annual prevalence and incidence were calculated among the Medicare beneficiaries by dividing the number of prevalent or incident LBD, DLB, and PDD patients by the total eligible population of that calendar year. Baseline patient characteristics, HCRU, and costs over time were described for Medicare and commercially insured patients with continuous health plan enrollment for ≥12 months before and ≥24 months after first cognitive impairment (CI) diagnosis. RESULTS: From 2010 to 2016, the incidence and prevalence rates of LBD among Medicare beneficiaries ranged from 0.21%-0.18% and 0.90%-0.83%, respectively. Of 9019 Medicare patients with LBD who met other inclusion criteria, 4796 (53.2%) had DLB and 4223 (46.8%) had PDD. The mean age was 78 years and the mean Charlson Comorbidity Index score was 1.6. On average, patients with LBD incurred $18,309 in medical costs during the 1-year pre-diagnosis and $29,174 and $22,814 at years 1 and 5 after diagnosis, respectively. The main cost drivers were inpatient and outpatient visits. Similar trends were observed for DLB and PDD as well as for commercially-insured patients. CONCLUSIONS: Our findings highlight the substantial epidemiological and economic burden across the LBD spectrum and underscore a high unmet need for effective treatments to improve patient outcomes.

Gait speed and survival in older adults.

CONTEXT: Survival estimates help individualize goals of care for geriatric patients, but life tables fail to account for the great variability in survival. Physical performance measures, such as gait speed, might help account for variability, allowing clinicians to make more individualized estimates. OBJECTIVE: To evaluate the relationship between gait speed and survival. DESIGN, SETTING, AND PARTICIPANTS: Pooled analysis of 9 cohort studies (collected between 1986 and 2000), using individual data from 34,485 community-dwelling older adults aged 65 years or older with baseline gait speed data, followed up for 6 to 21 years. Participants were a mean (SD) age of 73.5 (5.9) years; 59.6%, women; and 79.8%, white; and had a mean (SD) gait speed of 0.92 (0.27) m/s. MAIN OUTCOME MEASURES: Survival rates and life expectancy. RESULTS: There were 17,528 deaths; the overall 5-year survival rate was 84.8% (confidence interval [CI], 79.6%-88.8%) and 10-year survival rate was 59.7% (95% CI, 46.5%-70.6%). Gait speed was associated with survival in all studies (pooled hazard ratio per 0.1 m/s, 0.88; 95% CI, 0.87-0.90; P < .001). Survival increased across the full range of gait speeds, with significant increments per 0.1 m/s. At age 75, predicted 10-year survival across the range of gait speeds ranged from 19% to 87% in men and from 35% to 91% in women. Predicted survival based on age, sex, and gait speed was as accurate as predicted based on age, sex, use of mobility aids, and self-reported function or as age, sex, chronic conditions, smoking history, blood pressure, body mass index, and hospitalization. CONCLUSION: In this pooled analysis of individual data from 9 selected cohorts, gait speed was associated with survival in older adults.

Characteristics of Parkinson's Disease in Patients with and without Cognitive Impairment.

BACKGROUND: Characterizing patients with Parkinson's disease (PD) and cognitive impairment is important toward understanding their natural history. OBJECTIVE: Understand clinical, treatment, and cost characteristics of patients with PD pre- and post-cognitive impairment (memory loss/mild cognitive impairment/dementia or dementia treatment) recognition. METHODS: 2,711 patients with PD newly diagnosed with cognitive impairment (index) were identified using administrative claims data. They were matched (1:1) on age and gender to patients with PD and no cognitive impairment (controls). These two cohorts were compared on patient characteristics, healthcare resource utilization, and total median costs for 3 years pre- and post-index using Chi-square tests, t-tests, and Wilcoxon rank-sum tests. Logistic regression was used to identify factors predicting cognitive impairment. RESULTS: Comorbidity indices for patients with cognitive impairment increased during the 6-year study period, especially after the index. Enrollment in Medicare Advantage Prescription Drug plans vs. commercial (OR = 1.60), dual Medicare/Medicaid eligibility (OR = 1.36), cerebrovascular disease (OR = 1.24), and PD medication use (OR = 1.46) were associated with a new cognitive impairment diagnosis (all p < 0.05). A greater proportion of patients with cognitive impairment had hospitalizations and emergency department visits and higher median total healthcare costs than controls for each year pre- and post-index. CONCLUSION: In patients with PD newly diagnosed with cognitive impairment, comorbidity burden, hospitalizations, emergency department visits, and total costs peaked 1-year pre- and post-identification. These data coupled with recommendations for annual screening for cognitive impairment in PD support the early diagnosis and management of cognitive impairment in order to optimize care for patients and their caregivers.

Prevalence and predictors of vitamin D inadequacy amongst Lebanese osteoporotic women.

In Middle-Eastern countries, more particularly in Lebanon, the incidence of vitamin D deficiency has been found to be surprisingly high in schoolchildren and young individuals. However, the prevalence and risk factors for vitamin D inadequacy amongst Lebanese osteoporotic women seeking medical health care has never been studied. We analysed vitamin D-inadequacy risk factors among the 251 Lebanese postmenopausal osteoporotic women (from both Muslim and Christian communities) who participated in a vitamin D international epidemiological study. Vitamin D inadequacy prevalence (25-hydroxyvitamin D (25(OH)D) , 30 ng/ml) was 84.9%. 25(OH)D was negatively correlated with BMI (r 20.41; P<0.001) and positively correlated with educational level (r 0.37; P<0.001) and self-reported general health (r 0.17; P<0.01). No significant correlation was found with age and no seasonal variation was observed. There was no significant correlation between 25(OH)D and sun exposure index or vitamin D-rich food consumption. However, 25(OH)D strongly correlated with vitamin D supplement intake (r 0.48; P<0.0001). Muslim community participants had lower 25(OH)D levels compared with their Christian counterparts (P<0.001). They also had higher BMI, lower educational level and vitamin D supplement consumption and followed more frequently a dress code covering the arms (P<0.0001 for all variables). In a multivariate model, in Muslims, inadequate vitamin D supplements and a dress code covering the arms are the independent predictors of 25(OH)D inadequacy (P<0.001 for both variables). However, in Christians, the predictors are inadequate vitamin D supplements, high BMI and low educational level (P<0.001; P=002 and P=0.02 respectively). There is an urgent need to increase vitamin D supplement use in Middle-Eastern osteoporotic women, more particularly in those from the Muslim community.

Protein profiling of the dimorphic, pathogenic fungus, Penicillium marneffei.

BACKGROUND: Penicillium marneffei is a pathogenic fungus that afflicts immunocompromised individuals having lived or traveled in Southeast Asia. This species is unique in that it is the only dimorphic member of the genus. Dimorphism results from a process, termed phase transition, which is regulated by temperature of incubation. At room temperature, the fungus grows filamentously (mould phase), but at body temperature (37 degrees C), a uninucleate yeast form develops that reproduces by fission. Formation of the yeast phase appears to be a requisite for pathogenicity. To date, no genes have been identified in P. marneffei that strictly induce mould-to-yeast phase conversion. In an effort to help identify potential gene products associated with morphogenesis, protein profiles were generated from the yeast and mould phases of P. marneffei. RESULTS: Whole cell proteins from the early stages of mould and yeast development in P. marneffei were resolved by two-dimensional gel electrophoresis. Selected proteins were recovered and sequenced by capillary-liquid chromatography-nanospray tandem mass spectrometry. Putative identifications were derived by searching available databases for homologous fungal sequences. Proteins found common to both mould and yeast phases included the signal transduction proteins cyclophilin and a RACK1-like ortholog, as well as those related to general metabolism, energy production, and protection from oxygen radicals. Many of the mould-specific proteins identified possessed similar functions. By comparison, proteins exhibiting increased expression during development of the parasitic yeast phase comprised those involved in heat-shock responses, general metabolism, and cell-wall biosynthesis, as well as a small GTPase that regulates nuclear membrane transport and mitotic processes in fungi. The cognate gene encoding the latter protein, designated RanA, was subsequently cloned and characterized. The P. marneffei RanA protein sequence, which contained the signature motif of Ran-GTPases, exhibited 90% homology to homologous Aspergillus proteins. CONCLUSION: This study clearly demonstrates the utility of proteomic approaches to studying dimorphism in P. marneffei. Moreover, this strategy complements and extends current genetic methodologies directed towards understanding the molecular mechanisms of phase transition. Finally, the documented increased levels of RanA expression suggest that cellular development in this fungus involves additional signaling mechanisms than have been previously described in P. marneffei.

Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations.

UNLABELLED: A consensus meeting was convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) to provide recommendations for interpreting clinical importance of treatment outcomes in clinical trials of the efficacy and effectiveness of chronic pain treatments. A group of 40 participants from universities, governmental agencies, a patient self-help organization, and the pharmaceutical industry considered methodologic issues and research results relevant to determining the clinical importance of changes in the specific outcome measures previously recommended by IMMPACT for 4 core chronic pain outcome domains: (1) Pain intensity, assessed by a 0 to 10 numerical rating scale; (2) physical functioning, assessed by the Multidimensional Pain Inventory and Brief Pain Inventory interference scales; (3) emotional functioning, assessed by the Beck Depression Inventory and Profile of Mood States; and (4) participant ratings of overall improvement, assessed by the Patient Global Impression of Change scale. It is recommended that 2 or more different methods be used to evaluate the clinical importance of improvement or worsening for chronic pain clinical trial outcome measures. Provisional benchmarks for identifying clinically important changes in specific outcome measures that can be used for outcome studies of treatments for chronic pain are proposed. PERSPECTIVE: Systematically collecting and reporting the recommended information needed to evaluate the clinical importance of treatment outcomes of chronic pain clinical trials will allow additional validation of proposed benchmarks and provide more meaningful comparisons of chronic pain treatments.

Performance-based or self-report measures of physical function: which should be used in clinical trials of hip fracture patients?

OBJECTIVES: To assess the validity, sensitivity to change, and responsiveness of 3 self-report and 4 performance-based measures of physical function: activity measure for postacute care (AM-PAC) Physical Mobility and Personal Care scales, the Medical Outcomes Study 36-Item Short Form Health Survey Physical Function scale (SF-36 PF), the Physical Functional Performance test (PFP-10), the Short Physical Performance Battery (SPPB), a 4-meter gait speed, and the six-minute walk test (6MWT). DESIGN: A prospective observational study of patients after a hip fracture. Assessments were performed at baseline and 12 weeks postenrollment. SETTING: Inpatient and outpatient rehabilitation facilities in Norway, the United Kingdom, Sweden, Israel, Germany, the United States, Denmark, and Spain. PARTICIPANTS: A sample of study participants (N=108) who had a hip fracture. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Assessments of validity (known-groups, concurrent, construct, and predictive), sensitivity to change (effect size, standardized response mean [SRM], SE of measure, minimal detectable change (MDC), and responsiveness (optimal operating cut-points and area under the curve) between baseline and 12-week follow-up. RESULTS: All physical function measures achieved comparably acceptable levels of validity. Odds ratios in predicting patient Global Assessment of Improvement at 12 weeks were as follows: AM-PAC Physical Mobility scale, 5.3; AM-PAC Personal Care scale, 3.6; SF-36 PF, 4.3; SPPB, 2.0; PFP-10, 2.5; gait speed, 1.9; and 6MWT, 2.4. Effect sizes and SRM exceeded 1 SD for all 7 measures. Percent of patients who exceeded the MDC(90) at week 12 were as follows: AM-PAC Physical Mobility scale, 90%; AM-PAC Personal Care scale, 74%; SF-36 PF, 66%; SPPB, 36%; PFP-10, 75%; gait speed, 69%; and 6MWT, 75%. When evaluating responsiveness using the area under receiver operating curves for each measure, all measures had acceptable responsiveness, and no pattern emerged of superior responsiveness depending on the type of measure used. CONCLUSIONS: Findings reveal that the validity, sensitivity, and responsiveness of self-report measures of physical function are comparable to performance-based measures in a sample of patients followed after fracturing a hip. From a psychometric perspective, either type of functional measure would be suitable for use in clinical trials where improvement in function is an endpoint of interest. The selection of the most appropriate type of functional measure as the primary endpoint for a clinical trial will depend on other factors, such as the measure's feasibility or the strength of the association between the hypothesized mechanism of action of the study intervention and a functional outcome measure.

Epidemiology and correlates of osteoporotic fractures among type 2 diabetic patients.

This study analyzed data on 87,224 osteoporotic patients with up to 18 years of computerized medical history. Patients with osteoporosis and type 2 diabetes had higher bone density yet more fractures than non-diabetic osteoporotic patients. Fracture incidence among the diabetic patients was associated with retinopathy and cardiovascular disease, but not with diabetes duration. PURPOSE: Little is known about the association between type 2 diabetes mellitus (T2DM) and fragility fractures or the mechanism(s) involved. We examined fracture correlates among T2DM patients with osteoporosis. METHODS: We used electronic health records of an osteoporosis (OP) registry cross-linked with a diabetes registry of a large payer provider healthcare organization in Israel. A cross-sectional analysis compared osteoporosis patients with and without T2DM, and a longitudinal Cox proportional hazard regression was used to identify incident fracture correlates. RESULTS: As of December 2015 a total of 87,224 current OP patients were identified, of whom 15,700 (18%) had T2DM. The T2DM OP patients were characterized by older age (mean 74.6 vs. 69.5), more males (20.3 vs. 14.0%), and a higher rate of chronic comorbidities compared to OP without diabetes. All major OP fractures (hip, spine, humerus, and forearm) were significantly more prevalent among T2DM OP patients (44 vs. 32%), with an overall age-standardized ratio of 1.22 (95% CI 1.19 to 1.25) and 1.15 (95% CI 1.10 to 1.21) for females and males respectively. The average T-scores were higher (femur neck - 1.8 vs. - 1.9, total hip - 1.2 vs. - 1.6, and vertebrae - 1.3 vs. - 1.7) for the T2DM OP patients compared to the non-T2DM OP patients. Among women with coexisting T2DM and osteoporosis (n = 10,812), fracture incidence was significantly associated with retinopathy (HR = 1.24, 95% CI 1.05 to 1.47) and cardiovascular disease (HR = 1.22, 95% CI 1.10 to 1.36) after controlling for age, bone mineral density T-score, rheumatoid arthritis, glucocorticoids, alcohol, and smoking). CONCLUSION: This large population-based study confirms the higher fracture risk of osteoporotic patients with T2DM, as compared to osteoporotic patients without T2DM, despite higher bone mineral density levels. The presence of micro- and macrovascular disease appears to increase this risk.

Prevalence of Vitamin D Inadequacy Among Chinese Postmenopausal Women: A Nationwide, Multicenter, Cross-Sectional Study.

Purpose: We aimed to investigate the status of serum 25-hydroxyvitamin D [25(OH)D] among Chinese postmenopausal women in a multicenter cross-sectional study. Methods: Non-institutionalized postmenopausal women aged ≥55 years were recruited from urban and rural areas in 7 geographically different regions in China. Subject enrollment was executed during the summer and the winter. Vitamin D insufficiency and deficiency were defined as 25(OH)D < 30 and< 20 ng/ml, and was measured by liquid chromatography-tandem mass spectrometry. Women were referred to a dual-energy x-ray absorptiometry (DXA) if they had a medium-to-high fracture risk suggested by Osteoporosis Self-Assessment Tool for Asians (OSTA). Results: Among all subjects, 91.2% (1,535/1,684, 95%CI: 89.7, 92.5) had vitamin D insufficiency and 61.3% had vitamin D deficiency (1,033/1,684, 95%CI: 59.0, 63.7). The prevalence of vitamin D deficiency was significantly higher in urban dwellers (64.9 vs. 57.7% in rural, P = 0.002) and in winter-enrolled subjects (84.7 vs. 41.3% in summer, P < 0.0001). The prevalence of vitamin D inadequacy did not increase in trend by latitude and was numerically lower in women who had high fracture risk and osteoporosis. A non-curvilinear change of intact parathyroid hormone (iPTH) levels was observed at 25(OH)D >16.78 ng/mL. Conclusions: The prevalence of vitamin D inadequacy was remarkable among Chinese postmenopausal women and independent of fracture risk assessed by OSTA or osteoporosis suggested by DXA. Winter season, urban residence, however not latitude, were significantly associated with a higher likelihood of vitamin D deficiency. Optimal vitamin D status for iPTH and bone-related outcomes merits further investigation in this population.

Gait Speed Predicts Incident Disability: A Pooled Analysis.

BACKGROUND: Functional independence with aging is an important goal for individuals and society. Simple prognostic indicators can inform health promotion and care planning, but evidence is limited by heterogeneity in measures of function. METHODS: We performed a pooled analysis of data from seven studies of 27,220 community-dwelling older adults aged 65 or older with baseline gait speed, followed for disability and mortality. Outcomes were incident inability or dependence on another person in bathing or dressing; and difficulty walking » - ½ mile or climbing 10 steps within 3 years. RESULTS: Participants with faster baseline gait had lower rates of incident disability. In subgroups (defined by 0.2 m/s-wide intervals from <0.4 to ≥ 1.4 m/s) with increasingly greater gait speed, 3-year rates of bathing or dressing dependence trended from 10% to 1% in men, and from 15% to 1% in women, while mobility difficulty trended from 47% to 4% in men and 40% to 6% in women. The age-adjusted relative risk ratio per 0.1 m/s greater speed for bathing or dressing dependence in men was 0.68 (0.57-0.81) and in women: 0.74 (0.66-0.82); for mobility difficulty, men: 0.75 (0.68-0.82), women: 0.73 (0.67-0.80). Results were similar for combined disability and mortality. Effects were largely consistent across subgroups based on age, gender, race, body mass index, prior hospitalization, and selected chronic conditions. In the presence of multiple other risk factors for disability, gait speed significantly increased the area under the receiver operator characteristic curve. CONCLUSION: In older adults, gait speed predicts 3 year incidence of bathing or dressing dependence, mobility difficulty, and a composite outcome of disability and mortality.