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Introduction: Federally funded Alzheimer's Disease Centers in the United States have been using a standardized neuropsychological test battery as part of the National Alzheimer's Coordinating Center Uniform Data Set (UDS) since 2005. Version 3 (V3) of the UDS replaced the previous version (V2) in 2015. We compared V2 and V3 neuropsychological tests with respect to their ability to distinguish among the Clinical Dementia Rating (CDR) global scores of 0, 0.5, and 1., Methods: First, we matched participants receiving V2 tests (V2 cohort) and V3 tests (V3 cohort) in their cognitive functions using tests common to both versions. Then, we compared receiver-operating characteristic (ROC) area under the curve in differentiating CDRs for the remaining tests., Results: Some V3 tests performed better than V2 tests in differentiating between CDR 0.5 and 0, but the improvement was limited to Caucasian participants., Discussion: Further efforts to improve the ability for early identification of cognitive decline among diverse racial groups are required., Competing Interests: Hiroko H Dodge, Felicia C. Goldstein, Nicole I Wakim, Tamar Gefen, Merilee Teylan, Kwun CG Chan, Walter A. Kukull, Lisa L. Barnes, Bruno Giordani, Timothy M. Hughes, Joel H. Kramer, David A. Loewenstein, Daniel C Marson, Dan M Mungas, Bonnie C. Sachs, Monica Willis‐Parker, Katherine V Wild, John C. Morris, and Sandra Weintraub have no conflicts of interest to declare. David Salmon is a paid consultant for Aptinyx, Inc. and Biogen, Inc. Kathleen Welsh‐Bohmer received funding from Verasci as a contract through Duke University and funding from Takeda over the last 5 years (until May 2019) as part of a contract with Duke., (© 2020 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.)

It remains unclear what clinical features inform the accuracy of a clinical diagnosis of Alzheimer disease (AD). Data were obtained from the National Alzheimer's Coordinating Center to compare clinical and neuropathologic features among participants who did or did not have Alzheimer disease neuropathologic changes (ADNC) at autopsy. Participants (1854) had a clinical Alzheimer dementia diagnosis and ADNC at autopsy (Confirmed-AD), 204 participants had an AD diagnosis and no ADNC (AD-Mimics), and 253 participants had no AD diagnosis and ADNC (Unidentified-AD). Compared to Confirmed-AD participants, AD-Mimics had less severe cognitive impairment, while Unidentified-AD participants displayed more parkinsonian signs, depression, and behavioral problems. This study highlights the importance of developing a complete panel of biomarkers as a tool to inform clinical diagnoses, as clinical phenotypes that are typically associated with diseases other than AD may result in inaccurate diagnoses., (© 2020 American Association of Neuropathologists, Inc. All rights reserved.)

The field of dementia research is rapidly evolving, especially with regards to our understanding of the diversity of neuropathologic changes that underlie cognitive decline. Definitions and criteria for known conditions are being periodically revised and refined, and new findings are being made about neuropathologic features associated with dementia status. The database maintained by the National Alzheimer's Coordinating Center (NACC) offer researchers a robust, rapid, and statistically well-powered method to evaluate the implications of newly identified neuropathologic conditions with regards to comorbidities, demographic associations, cognitive status, neuropsychologic tests, radiographic findings, and genetics. NACC data derive from dozens of excellent US Alzheimer disease research centers, which collectively follow thousands of research volunteers longitudinally. Many of the research participants are autopsied using state-of-the-art methods. In this article, we describe the NACC database and give examples of its use in evaluating recently revised neuropathologic diagnoses, including primary age-related tauopathy (PART), limbic predominant age-related TDP-43 encephalopathy (LATE), and the preclinical stage of Alzheimer disease neuropathologic change, based on the National Institute on Aging-Alzheimer's Association consensus guidelines. The dementia research community is encouraged to make use of this readily available database as new neuropathologic changes are recognized and defined in this rapidly evolving field.

Study Design: Observational study., Objective: Assess associations between vitamin D levels and other risk factors on future chest illness in a chronic spinal cord injury (SCI) cohort., Setting: Veterans Affairs Boston and the Boston, MA community., Methods: Between August 2009 and August 2017, 253 participants with chronic SCI were followed over a median of 3.2 years (up to 7.4 years) with two to four visits a median of 1.7 years apart. At each visit, plasma 25-hydroxyvitamin D level was obtained, spirometry performed, and a respiratory questionnaire assessing chest illnesses since last visit was completed. Repeated measures negative binomial regression was used to assess chest illness risk longitudinally., Results: At entry, 25% had deficient vitamin D levels (<20 nanograms/milliliter (ng/ml)), 52% were insufficient (20 to <30 ng/ml), and 23% were sufficient (≥30 ng/ml). Over 545 study visits, chest illnesses (n = 106) were reported by 60 participants. In multivariable models (including previous chest illness history), deficient vitamin D levels (compared with those with sufficient levels) were associated with future chest illness though with wide confidence limits (relative risk (RR) = 1.36, 95% confidence intervals (CI) = 0.74, 2.47). The strongest association with chest illness during the follow-up period was in persons who reported pneumonia/bronchitis after injury and a chest illness in the three years before study entry (RR = 7.62; 95% CI = 3.70, 15.71)., Conclusion: Assessed prospectively in chronic SCI, there was a suggestive association between deficient vitamin D levels and future chest illness. Past chest illness history was also strongly associated with future chest illness.

Objective: To compare the proportion of APOE ε4 genotype carriers in aphasic vs amnestic variants of Alzheimer disease (AD)., Method: The proportion of APOE ε4 carriers was compared among the following 3 groups: (1) 42 patients with primary progressive aphasia (PPA) and AD pathology (PPA/AD) enrolled in the Northwestern Alzheimer Disease Center Clinical Core; (2) 1,418 patients with autopsy-confirmed AD and amnestic dementia of the Alzheimer type (DAT/AD); and (3) 2,608 cognitively normal controls (NC). The latter 2 groups were compiled from the National Alzheimer Coordinating Center database. Logistic regression models analyzed the relationship between groups and APOE ε4 carrier status, adjusting for age at onset and sex as needed., Results: Using NC as the reference and adjusting for sex and age, the DAT/AD group was 3.97 times more likely to be APOE ε4 carriers. Adjusting for sex and age at symptom onset, the DAT/AD group was 2.46 times as likely to be carriers compared to PPA/AD. There was no significant difference in the proportion of APOE ε4 carriers for PPA/AD compared to NC. PPA subtypes included 24 logopenic, 10 agrammatic nonfluent, and 8 either mixed (n = 5) or too severe (n = 3) to subtype. The proportion of carriers and noncarriers was similar for logopenic and agrammatic subtypes, both having fewer carriers., Conclusion: The proportion of APOE ε4 carriers was elevated in amnestic but not aphasic manifestations of AD. These results suggest that APOE ε4 is an anatomically selective risk factor that preferentially increases the vulnerability to AD pathology of memory-related medial temporal areas rather than language-related neocortices., (© 2019 American Academy of Neurology.)

Primary age-related tauopathy is increasingly recognized as a separate neuropathological entity different from Alzheimer's disease. Both share the neuropathological features of tau aggregates and neuronal loss in the temporal lobe, but primary age-related tauopathy lacks the requisite amyloid plaques central to Alzheimer's disease. While both have similar clinical presentations, individuals with symptomatic primary age-related tauopathy are commonly of more advanced ages with milder cognitive dysfunction. Direct comparison of the neuropsychological trajectories of primary age-related tauopathy and Alzheimer's disease has not been thoroughly evaluated and thus, our objective was to determine how cognitive decline differs longitudinally between these two conditions after the onset of clinical symptoms. Data were obtained from the National Alzheimer's Coordinating Center on participants with mild cognitive impairment at baseline and either no neuritic plaques (i.e. primary age-related tauopathy) or moderate to frequent neuritic plaques (i.e. Alzheimer neuropathological change) at subsequent autopsy. For patients with Alzheimer's disease and primary age-related tauopathy, we compared rates of decline in the sum of boxes score from the CDR® Dementia Staging Instrument and in five cognitive domains (episodic memory, attention/working memory, executive function, language/semantic memory, and global composite) using z-scores for neuropsychological tests that were calculated based on scores for participants with normal cognition. The differences in rates of change were tested using linear mixed-effects models accounting for clinical centre clustering and repeated measures by individual. Models were adjusted for sex, age, education, baseline test score, Braak stage, apolipoprotein ε4 (APOE ε4) carrier status, family history of cognitive impairment, and history of stroke, hypertension, or diabetes. We identified 578 participants with a global CDR of 0.5 (i.e. mild cognitive impairment) at baseline, 126 with primary age-related tauopathy and 452 with Alzheimer's disease. Examining the difference in rates of change in CDR sum of boxes and in all domain scores, participants with Alzheimer's disease had a significantly steeper decline after becoming clinically symptomatic than those with primary age-related tauopathy. This remained true after adjusting for covariates. The results of this analysis corroborate previous studies showing that primary age-related tauopathy has slower cognitive decline than Alzheimer's disease across multiple neuropsychological domains, thus adding to the understanding of the neuropsychological burden in primary age-related tauopathy. The study provides further evidence to support the hypothesis that primary age-related tauopathy has distinct neuropathological and clinical features compared to Alzheimer's disease., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Primary age-related tauopathy (PART) is increasingly recognized as a pathologic entity distinct from Alzheimer's disease (AD). Given that the diagnosis of PART is an autopsy diagnosis, it is unclear how PART is perceived in clinical practice. Thus, we investigated the presumptive primary and contributing diagnoses in individuals who had cognitive impairment while alive and who met neuropathologic criteria for PART at autopsy. We also compared these clinical diagnoses for people with PART to those with AD neuropathology (ADNP). We used data on 1354 participants from the National Alzheimer's Coordinating Center, restricting to those with no neuritic plaques (PART) or moderate/frequent neuritic plaques (ADNP); clinical visit within two years of autopsy; and mild cognitive impairment (MCI) or dementia at last visit. To assess if PART participants were less likely to receive a clinical diagnosis of AD at their last visit prior to autopsy, we used logistic regression, controlling for age, sex, education, and APOE ε4 status. There were 161 PART individuals (n = 49 MCI; n = 112 dementia) and 1193 individuals with ADNP (n = 75 MCI; n = 1118 dementia). Primary clinical diagnosis of AD was more common in those with ADNP (MCI: 69%; demented: 86%) than PART (MCI: 57%; demented: 52%). In the adjusted analysis, primary and contributing clinical diagnoses of AD remained less likely in PART vs. ADNP participants with dementia (OR: 0.22, 95% CI: 0.13-0.38). This study suggests that clinicians recognize a distinction in the clinical presentation between PART and ADNP, diagnosing AD less frequently in those with PART. Nonetheless, clinical AD was diagnosed greater than 50% of the time in PART participants with MCI or dementia. Ante-mortem criteria for diagnosis of PART need to be established, as PART is a neuropathological entity that is distinct from AD and has its own clinical and cognitive outcomes.

Estimates of the minimal clinically important difference (MCID) for physical activity (PA) in chronic obstructive pulmonary disease (COPD) are needed. The objective is to provide an anchor-based estimate of the MCID for daily step count. PA was promoted in persons with COPD using a pedometer (Omron HJ-720ITC) alone or a pedometer plus interactive website for 3 months. Participants wore the pedometer daily and received phone calls monthly to ascertain medical events. Medical events were counted when a participant self-reported that he/she had (1) worsening of breathing, (2) change to breathing medications, (3) medical care from an emergency room for any reason, or (4) hospitalization for any reason. Generalized linear regression models assessed daily step count as change at the end of study and averaged over the 15, 31, or 61 days centered on the event, in those with an event compared to those without one. All categories of events carried equal weight in the analyses. We studied 93 persons, 46 of whom had an event. Participants who experienced an event had a decrease of 1086 (95% confidence interval (CI): -2124 to -48) or 887 (95% CI: -2030 to 257) steps/day in the pedometer plus website or pedometer alone groups, respectively, compared to those without one. In the days centered on an event, participants who had an event experienced a decrease of 882-983 steps/day (pedometer plus website) or a decrease of 351-495 steps/day (pedometer alone), compared to those without one. The MCID for PA in COPD ranges from 350 steps/day to 1100 steps/day.

Context/Objective Persons with chronic spinal cord injury (SCI) have an increased risk of respiratory-related morbidity and mortality and chronic respiratory symptoms are clinical markers of future respiratory disease. Therefore, we sought to assess potentially modifiable factors associated with respiratory symptoms, with a focus on circulating vitamin D and measures of body fat. Design Cross-sectional study. Setting Veterans Affairs Medical Center. Participants Three hundred forty-three participants (282 men and 61 women) with chronic SCI participating in an epidemiologic study to assess factors influencing respiratory health recruited from VA Boston and the community. Methods Participants provided a blood sample, completed a respiratory health questionnaire, and underwent dual x-ray absorptiometry (DXA) to assess % body fat. Logistic regression was used to assess cross-sectional associations between respiratory symptoms and plasma vitamin D and measures of body fat with adjustment for a number of potential confounders. Outcome Measures Chronic cough, chronic phlegm, any wheeze, persistent wheeze. Results After adjustment for a number of confounders (including smoking), participants with greater %-android, gynoid, trunk, or total body fat had increased odds ratios for any wheeze and suggestive associations with persistent wheeze, but not with chronic cough or phlegm. Vitamin D levels were not associated with any of the respiratory symptoms. Conclusion Increased body fat, but not vitamin D, was associated with wheeze in chronic SCI independent of a number of covariates.

Introduction: In 2015, the US Alzheimer's Disease Centers (ADC) implemented Version 3 of the Uniform Data Set (UDS). This paper describes the history of Version 3 development and the UDS data that are freely available to researchers., Methods: UDS Version 3 was developed after years of coordination between the National Institute on Aging-appointed Clinical Task Force (CTF), clinicians from ∼30 ADCs, and the National Alzheimer's Coordinating Center (NACC). The CTF recognized the need for updates to align with the state of the science in dementia research, while being flexible to the diverse needs and diseases studied at the ADCs. Version 3 also developed a nonproprietary neuropsychological battery., Results: This paper focuses on the substantial Version 3 changes to the UDS forms related to clinical diagnosis and characterization of clinical symptoms to match updated consensus-based diagnostic criteria. Between March 2015 and March 2018, 4820 participants were enrolled using UDS Version 3. Longitudinal data were available for 25,337 of the 37,568 total participants using all UDS versions., Discussion: The results from utilization of the UDS highlight the possibility for numerous research institutions to successfully collaborate, produce, and use standardized data collection instruments for over a decade.

Background: Adipose tissue produces leptin, which is pro-inflammatory, and adiponectin, which has anti-inflammatory properties. Participants with chronic spinal cord injury (SCI) have increased body fat and are at increased risk for respiratory illness., Objective: To assess the associations between leptin and adiponectin with pulmonary function in a chronic SCI cohort., Design: Cross-sectional study., Setting: Veterans Affairs Medical Center., Participants: A total of 285 participants (237 men and 48 women) with chronic SCI with mean (standard deviation) injury duration 17.8 (13.2) years from the VA Boston and the community participating in an epidemiologic study assessing factors associated with respiratory health., Methods: Participants (24.6% cervical American Spinal Injury Association Impairment Scale (AIS) level A, B, and C; 33.6% other AIS A, B, and C; 41.8% AIS D) provided a blood sample, completed a respiratory health questionnaire, and underwent spirometry. Linear regression methods were used to assess cross-sectional associations between plasma leptin and adiponectin with spirometric measures of pulmonary function adjusted for age, race, gender, and height. Level and severity of SCI, mobility mode, body mass index, smoking, chronic obstructive pulmonary disease, asthma, chest injury history, laboratory batch, and other potential confounders were also considered., Main Outcome Measurements: forced expiratory volume in 1 second (FEV 1 ), forced vital capacity (FVC), and FEV 1 /FVC., Results: There was a statistically significant inverse relationship between plasma leptin assessed in quartiles or as a continuous covariate with FEV 1 and FVC. In fully adjusted models, each interquartile range (16,214 pg/mL) increase in leptin was associated with a significant decrease in FEV 1 (-93.1 mL; 95% confidence interval = -166.2, -20.0) and decrease in FVC (-130.7 mL; 95% confidence interval = -219.4, -42.0). There were no significant associations between leptin and FEV 1 /FVC or between plasma adiponectin with FEV 1 , FVC, or FEV 1 /FVC., Conclusion: Plasma leptin in individuals with chronic SCI is inversely associated with FEV 1 and FVC, independently of SCI level and severity and other covariates. This finding suggests that plasma leptin may contribute to reduced pulmonary function in chronic SCI., Level of Evidence: II., (Copyright © 2018 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.)

Introduction: The neuropsychological battery of the Uniform Data Set (UDSNB) was implemented in 2005 by the National Institute on Aging (NIA) Alzheimer Disease Centers program to measure cognitive performance in dementia and mild cognitive impairment due to Alzheimer Disease. This paper describes a revision, the UDSNB 3.0., Methods: The Neuropsychology Work Group of the NIA Clinical Task Force recommended revisions through a process of due diligence to address shortcomings of the original battery. The UDSNB 3.0 covers episodic memory, processing speed, executive function, language, and constructional ability. Data from 3602 cognitively normal participants in the National Alzheimer Coordinating Center database were analyzed., Results: Descriptive statistics are presented. Multivariable linear regression analyses demonstrated score differences by age, sex, and education and were also used to create a normative calculator available online., Discussion: The UDSNB 3.0 neuropsychological battery provides a valuable non proprietary resource for conducting research on cognitive aging and dementia.

Rationale: Low physical activity is highly prevalent among COPD patients and is associated with increased healthcare utilization and mortality and reduced HRQL. The addition of a website to pedometer use is effective at increasing physical activity; however, the timeline of change and impact of environmental factors on efficacy is unknown., Methods: U.S. Veterans with COPD were randomized (1:1) to receive either (1) a pedometer and website which provided goal-setting, feedback, disease-specific education, and an online community forum or (2) pedometer alone for 3 months. Primary outcome was change in daily step count. Secondary outcomes included 6MWT distance, HRQL, dyspnea, depression, COPD knowledge, exercise self-efficacy, social support, motivation, and confidence to exercise. Generalized linear mixed-effects models evaluated the effect of the pedometer plus website compared to pedometer alone., Results: Data from 109 subjects (98.5% male, mean age 68.6 ± 8.3 years) were analyzed. At 13 weeks, subjects in the pedometer plus website group had significant increases daily step count from baseline relative to the pedometer alone group (804 ± 356.5 steps per day, p = 0.02). The pedometer plus website group had significant improvements in daily step count from baseline beginning in week 3 which were sustained until week 13. In subgroup analyses, the pedometer plus website attenuated declines in daily step count during the transition from summer to fall. No significant differences in secondary outcomes were noted between groups., Conclusions: A website added to pedometer use improves daily step counts, sustains walking over 3 months, and attenuates declines in physical activity due to season., (Published by Elsevier Ltd.)

Background: Systemic inflammation has been associated with reduced pulmonary function in individuals with and without chronic medical conditions. Individuals with chronic spinal cord injury (SCI) have clinical characteristics that promote systemic inflammation and also have reduced pulmonary function. We sought to assess the associations between biomarkers of systemic inflammation with pulmonary function in a chronic SCI cohort, adjusting for other potential confounding factors., Methods: Participants (n = 311) provided a blood sample, completed a respiratory health questionnaire, and underwent spirometry. Linear regression methods were used to assess cross-sectional associations between plasma C-reactive protein (CRP) and interleukin-6 (IL-6) with forced expiratory volume in one second (FEV 1 ), forced vital capacity (FVC), and FEV 1 /FVC., Results: There were statistically significant inverse relationships between plasma CRP and IL-6 assessed in quartiles or continuously with FEV 1 and FVC. In fully adjusted models, each interquartile range (5.91 mg/L) increase in CRP was associated with a significant decrease in FEV 1 (-55.85 ml; 95% CI: -89.21, -22.49) and decrease in FVC (-65.50 ml; 95% CI: -106.61, -24.60). There were similar significant findings for IL-6. There were no statistically significant associations observed with FEV 1 /FVC., Conclusion: Plasma CRP and IL-6 in individuals with chronic SCI are inversely associated with FEV 1 and FVC, independent of SCI level and severity of injury, BMI, and other covariates. This finding suggests that systemic inflammation associated with chronic SCI may contribute to reduced pulmonary function.

One possible approach to prevention of suicide attempts is to encourage help-seeking among individuals at risk. We assessed whether different forms of treatment were associated with lower odds of a suicide attempt in a diverse group of 388 lesbian, gay, and bisexual (LGB) adults aged 18-59, sampled from New York City venues. Of individuals who attempted suicide, 23% sought mental health or medical treatment and 14% sought religious or spiritual treatment prior to the suicide attempt. Black and Latino LGBs were underrepresented in mental health or medical treatment and Black LGBs were overrepresented in religious or spiritual treatment. Seeking mental health or medical treatment was not associated with lower odds of a suicide attempt; seeking religious or spiritual treatment was associated with higher odds of a suicide attempt. We discuss these results and posit hypotheses for further research of this understudied topic., (© 2014 The American Association of Suicidology.)

Objective assessment of physical activity (PA) in chronic obstructive pulmonary disease (COPD) is important. We examined the performance of the Omron HJ-720ITC pedometer. A sample of 176 persons with stable COPD wore the Omron and the StepWatch Activity Monitor (SAM) in the clinic and the community. A 4 s step filter in the Omron screens out erroneous intermittent steps; it captures continuous walking that lasts >4 s. The SAM captures all intermittent and continuous steps walked. Omron-steps were compared with manually counted steps in the clinic and with SAM-steps in the community. We calculated the intraclass correlation coefficient for the first 2 d, the first 3 d, etc., up to 14 d. The Omron registered >/= 90% of the manually counted steps from the in-clinic walk in 155 of 176 subjects (88%). In the community, 47 +/- 16% of SAM-steps were continuous ones that were captured by the Omron. For the Omron and the SAM, at least 7 d of monitoring should be used to capture decreases in PA on weekend days and obtain optimum reliability for all Global Initiative for Chronic Obstructive Lung Disease stages. The Omron accurately and reliably measures continuous walking in COPD. The Omron may be ideal for use in PA interventions that promote continuous walking as exercise.

Background: Physical activity is an important clinical marker of disease status in COPD. COPD is also characterized by low-grade systemic inflammation. However, the relationship between physical activity and systemic inflammation in COPD is unclear., Methods: We monitored daily step count, a directly measured physical activity, using the StepWatch Activity Monitor, an ankle-worn accelerometer, in 171 people with stable COPD. Exercise capacity was assessed with the 6-min walk test (6MWT). We measured plasma C-reactive protein (CRP) and IL-6 levels. Linear regression models examined the cross-sectional associations of daily step count and 6MWT distance with CRP and IL-6 levels., Results: Subjects had a mean age 72±8 years and mean FEV1 1.5±0.57 L (54±20% predicted). Median daily step count was 5,203 (interquartile range [IQR], 3,627-7,024], CRP level was 2.4 mg/L (IQR, 1.2-5.0), and IL-6 level was 2.9 pg/mL (IQR, 2.0-5.1). Each 1,000-step increase in daily step count was associated with a 0.94 mg/L and 0.96 pg/mL decrease in CRP (P=.020) and IL-6 (P=.044) levels, respectively, adjusting for age, FEV1 % predicted, pack-years smoked, cardiac disease, current statin use, history of acute exacerbations, and season. There was a significant linear trend of increasing daily step count by quartiles and decreasing CRP (P=.0007) and IL-6 (P=.023) levels. Higher 6MWT distance was also significantly associated with lower CRP and IL-6 values., Conclusion: People with COPD who walked the most had the lowest plasma CRP and IL-6 levels. These results provide the conceptual basis to study whether an intervention to promote walking will reduce systemic inflammation in people with COPD.

Background: Identification of persons with chronic obstructive pulmonary disease (COPD) at risk for acute exacerbations (AEs) targets them for close monitoring., Objectives: We examined the ability of a novel index combining physical activity and systemic inflammation to identify persons at risk for AEs., Methods: In an observational cohort study of 167 persons with COPD, we assessed daily step count, a direct measure of physical activity, with the StepWatch Activity Monitor and measured plasma C-reactive protein (CRP) and IL-6 levels. AEs and COPD-related hospitalizations were assessed prospectively over a median of 16 months. Predictors of AEs and COPD-related hospitalizations were assessed using negative binomial models., Measurements and Main Results: Median daily step count was 5,203 steps (interquartile range, 3,627-7,024). Subjects with daily step count ≤ 5,203 and CRP > 3 mg/l had an increased rate of AEs (rate ratio [RR], 2.06; 95% confidence interval [CI], 1.30-3.27) and COPD-related hospitalizations (RR, 3.51; 95% CI, 1.73-7.11) compared with subjects with daily step count > 5,203 and CRP ≤ 3 mg/l, adjusting for FEV1% predicted and prednisone use for AE in the previous year. Similarly, subjects with daily step count ≤ 5,203 and IL-6 > 2 pg/ml had an increased rate of AEs (RR, 2.04; 95% CI, 1.14-3.63) and COPD-related hospitalizations (RR, 4.27; 95% CI, 1.56-11.7) compared with subjects with daily step count > 5,203 and IL-6 ≤ 2 pg/ml., Conclusions: An index combining daily step count and systemic inflammation can predict AEs and COPD-related hospitalizations. A validation study in a separate cohort is needed to confirm the utility of the proposed index as a clinical tool to risk stratify persons with COPD.

Background: COPD is characterized by variability in exercise capacity and physical activity (PA), and acute exacerbations (AEs). Little is known about the relationship between daily step count, a direct measure of PA, and the risk of AEs, including hospitalizations., Methods: In an observational cohort study of 169 persons with COPD, we directly assessed PA with the StepWatch Activity Monitor, an ankle-worn accelerometer that measures daily step count. We also assessed exercise capacity with the 6-minute walk test (6MWT) and patient-reported PA with the St. George's Respiratory Questionnaire Activity Score (SGRQ-AS). AEs and COPD-related hospitalizations were assessed and validated prospectively over a median of 16 months., Results: Mean daily step count was 5804±3141 steps. Over 209 person-years of observation, there were 263 AEs (incidence rate 1.3±1.6 per person-year) and 116 COPD-related hospitalizations (incidence rate 0.56±1.09 per person-year). Adjusting for FEV1 % predicted and prednisone use for AE in previous year, for each 1000 fewer steps per day walked at baseline, there was an increased rate of AEs (rate ratio 1.07; 95%CI = 1.003-1.15) and COPD-related hospitalizations (rate ratio 1.24; 95%CI = 1.08-1.42). There was a significant linear trend of decreasing daily step count by quartiles and increasing rate ratios for AEs (P = 0.008) and COPD-related hospitalizations (P = 0.003). Each 30-meter decrease in 6MWT distance was associated with an increased rate ratio of 1.07 (95%CI = 1.01-1.14) for AEs and 1.18 (95%CI = 1.07-1.30) for COPD-related hospitalizations. Worsening of SGRQ-AS by 4 points was associated with an increased rate ratio of 1.05 (95%CI = 1.01-1.09) for AEs and 1.10 (95%CI = 1.02-1.17) for COPD-related hospitalizations., Conclusions: Lower daily step count, lower 6MWT distance, and worse SGRQ-AS predict future AEs and COPD-related hospitalizations, independent of pulmonary function and previous AE history. These results support the importance of assessing PA in patients with COPD, and provide the rationale to promote PA as part of exacerbation-prevention strategies.