The Collaborative Aging Research Using Technology Initiative: An Open, Sharable, Technology-Agnostic Platform for the Research Community.

INTRODUCTION: Future digital health research hinges on methodologies to conduct remote clinical assessments and in-home monitoring. The Collaborative Aging Research Using Technology (CART) initiative was introduced to establish a digital technology research platform that could widely assess activity in the homes of diverse cohorts of older adults and detect meaningful change longitudinally. This paper reports on the built end-to-end design of the CART platform, its functionality, and the resulting research capabilities. METHODS: CART platform development followed a principled design process aiming for scalability, use case flexibility, longevity, and data privacy protection while allowing sharability. The platform, comprising ambient technology, wearables, and other sensors, was deployed in participants' homes to provide continuous, long-term (months to years), and ecologically valid data. Data gathered from CART homes were sent securely to a research server for analysis and future data sharing. RESULTS: The CART system was created, iteratively tested, and deployed to 232 homes representing four diverse cohorts (African American, Latinx, low-income, and predominantly rural-residing veterans) of older adults (n = 301) across the USA. Multiple measurements of wellness such as cognition (e.g., mean daily computer use time = 160-169 min), physical mobility (e.g., mean daily transitions between rooms = 96-155), sleep (e.g., mean nightly sleep duration = 6.3-7.4 h), and level of social engagement (e.g., reports of overnight visitors = 15-45%) were collected across cohorts. CONCLUSION: The CART initiative resulted in a minimally obtrusive digital health-enabled system that met the design principles while allowing for data capture over extended periods and can be widely used by the research community. The ability to monitor and manage health digitally within the homes of older adults is an important alternative to in-person assessments in many research contexts. Further advances will come with wider, shared use of the CART system in additional settings, within different disease contexts, and by diverse research teams.

Sex and genetic differences in postoperative cognitive dysfunction: a longitudinal cohort analysis.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common postoperative complication experienced by patients aged 65 years and older, and these older adults comprise more than one third of the surgical patients in the USA. Because not everyone with a history of exposure to surgery and anesthesia develops POCD, there are likely major biological risk factors involved. There are important gaps in our knowledge regarding whether genetic makeup, biological sex, or other Alzheimer's disease risk factors predispose older adults to developing POCD. We set out to determine whether biological sex and Apolipoprotein E-ε4 (APOE4) carrier status increase the risk of developing POCD in older adults. METHODS: We performed a cohort analysis of 1033 participants of prospective longitudinal aging studies. Participants underwent regular cognitive test batteries and we compared the annual rate of change over time in various cognitive measures in the women exposed to surgery and general anesthesia compared to the men exposed to surgery and general anesthesia. Mixed-effects statistical models were used to assess the relationship between biological sex, APOE4 carrier status, surgery and anesthesia exposure, and the rate of change in cognitive test scores. RESULTS: When comparing all men (n = 89) and women (n = 164) who had surgery, there were no significant sex differences in postoperative cognitive outcomes. However, men with an APOE4 allele performed significantly worse on cognitive testing following surgery and anesthesia than women APOE4 carriers, even after adjusting for age, education level, and comorbidities. CONCLUSIONS: Older men with APOE4 allele may be more vulnerable to postoperative cognitive dysfunction than older women with APOE4 allele.

Surgery is associated with ventricular enlargement as well as cognitive and functional decline.

INTRODUCTION: In preclinical studies, surgery/anesthesia contribute to cognitive decline and enhance neuropathologic changes underlying Alzheimer's disease (AD). Nevertheless, the link between surgery, anesthesia, apolipoprotein E ε4 (APOE ε4), and AD remains unclear. METHODS: We performed a retrospective cohort analysis of two prospective longitudinal aging studies. Mixed-effects statistical models were used to assess the relationship between surgical/anesthetic exposure, the APOE genotype, and rate of change in measures of cognition, function, and brain volumes. RESULTS: The surgical group (n = 182) experienced a more rapid rate of deterioration compared with the nonsurgical group (n = 345) in several cognitive, functional, and brain magnetic resonance imaging measures. Furthermore, there was a significant synergistic effect of anesthesia/surgery exposure and presence of the APOE ε4 allele in the decline of multiple cognitive and functional measures. DISCUSSION: These data provide insight into the role of surgical exposure as a risk factor for cognitive and functional decline in older adults.

Use of High-Frequency In-Home Monitoring Data May Reduce Sample Sizes Needed in Clinical Trials.

BACKGROUND: Trials in Alzheimer's disease are increasingly focusing on prevention in asymptomatic individuals. This poses a challenge in examining treatment effects since currently available approaches are often unable to detect cognitive and functional changes among asymptomatic individuals. Resultant small effect sizes require large sample sizes using biomarkers or secondary measures for randomized controlled trials (RCTs). Better assessment approaches and outcomes capable of capturing subtle changes during asymptomatic disease stages are needed. OBJECTIVE: We aimed to develop a new approach to track changes in functional outcomes by using individual-specific distributions (as opposed to group-norms) of unobtrusive continuously monitored in-home data. Our objective was to compare sample sizes required to achieve sufficient power to detect prevention trial effects in trajectories of outcomes in two scenarios: (1) annually assessed neuropsychological test scores (a conventional approach), and (2) the likelihood of having subject-specific low performance thresholds, both modeled as a function of time. METHODS: One hundred nineteen cognitively intact subjects were enrolled and followed over 3 years in the Intelligent Systems for Assessing Aging Change (ISAAC) study. Using the difference in empirically identified time slopes between those who remained cognitively intact during follow-up (normal control, NC) and those who transitioned to mild cognitive impairment (MCI), we estimated comparative sample sizes required to achieve up to 80% statistical power over a range of effect sizes for detecting reductions in the difference in time slopes between NC and MCI incidence before transition. RESULTS: Sample size estimates indicated approximately 2000 subjects with a follow-up duration of 4 years would be needed to achieve a 30% effect size when the outcome is an annually assessed memory test score. When the outcome is likelihood of low walking speed defined using the individual-specific distributions of walking speed collected at baseline, 262 subjects are required. Similarly for computer use, 26 subjects are required. CONCLUSIONS: Individual-specific thresholds of low functional performance based on high-frequency in-home monitoring data distinguish trajectories of MCI from NC and could substantially reduce sample sizes needed in dementia prevention RCTs.

Associations between observed in-home behaviors and self-reported low mood in community-dwelling older adults.

OBJECTIVES: To ascertain the association between self-report of low mood and unobtrusively measured behaviors (walking speed, time out of residence, frequency of room transitions, and computer use) in community-dwelling older adults using novel monitoring technologies. DESIGN: Longitudinal cohort study of older adults whose homes were outfitted with activity sensors. Participants completed Internet-based weekly health questionnaires with questions about mood. SETTING: Apartments and homes of older adults living in the Portland, Oregon, metropolitan area. PARTICIPANTS: Adults, average age 84, followed for an average of 3.7 years (n = 157). MEASUREMENTS: Mood was assessed according to self-report each week. Walking speed, time spent out of residence, and room transitions were estimated using data from sensors; computer use was measured by timing actual use. The association between global or weekly low mood and the four behavior measures was ascertained, adjusting for baseline characteristics. RESULTS: Eighteen thousand nine hundred sixty weekly observations of mood were analyzed; 2.6% involved low mood. Individuals who reported low mood more often had no average differences in any behavior parameters from those who reported low mood less often. During weeks when they reported low mood, participants spent significantly less time out of residence and on the computer but showed no change in walking speed or room transitions. CONCLUSION: Low mood in these community-dwelling older adults involved going out of the house less and using the computer less but no consistent changes in movements. Technologies to monitor in-home behavior may have potential for research and clinical care.

Social activity decreases risk of placement in a long-term care facility for a prospective sample of community-dwelling older adults.

The purpose of this study was to determine the role of modifiable factors in the risk of long-term care (LTC) placement. Using data from a cohort of community-residing older adults (N = 189), a secondary analysis was conducted of the contribution of social activity, sleep disturbances, and depressive symptoms to the risk of LTC placement. Analyses controlled for cognitive and functional impairment, age, and medical conditions. Within 5 years, 20% of participants were placed in a LTC facility. Each unit increase in social activity was associated with a 24% decrease in the risk of placement (odds ratio [OR] = 0.763, p = 0.001, 95% confidence interval [CI] [0.65, 0.89]). Cognitive impairment (OR = 3.05, p = 0.017, 95% CI [1.23, 7.59]), medical conditions (OR = 1.22, p = 0.039, 95% CI [1.01, 1.47]), and age (OR = 1.101, p = 0.030, 95% CI [1.01, 1.20]) were also significant individual predictors of placement. Although many of the strongest risk factors for placement are not modifiable, older adults who engage in more social activity outside the home may be able to delay transition from independent living.

Computer-related self-efficacy and anxiety in older adults with and without mild cognitive impairment.

BACKGROUND: This study examines differences in computer-related self-efficacy and anxiety in subgroups of older adults, and changes in those measures after exposure to a systematic training program and subsequent computer use. METHODS: Participants were volunteers in the Intelligent Systems for Assessment of Aging Changes study (ISAAC) carried out by the Oregon Center for Aging and Technology. Participants were administered two questionnaires before training and again 1 year later, which were related to computer self-efficacy and anxiety. Continuous recording of computer use was also assessed for a subset of participants. RESULTS: Baseline comparisons by sex, age, education, living arrangement, and computer proficiency, but not cognitive status, yielded significant differences in confidence and anxiety related to specific aspects of computer use. At 1-year follow-up, participants reported less anxiety and greater confidence. However, the benefits of training and exposure varied by group and task. Comparisons based on cognitive status showed that the cognitively intact participants benefited more from training and/or experience with computers than did participants with mild cognitive impairment (MCI), who after 1 year continued to report less confidence and more anxiety regarding certain aspects of computer use. CONCLUSION: After 1 year of consistent computer use, cognitively intact participants in this study reported reduced levels of anxiety and increased self-confidence in their ability to perform specific computer tasks. Participants with MCI at baseline were less likely to demonstrate increased efficacy or confidence than their cognitively intact counterparts.

Executive function predicts risk of falls in older adults without balance impairment.

BACKGROUND: Executive dysfunction has previously been found to be a risk factor for falls. The aim of this study is to investigate the association between executive dysfunction and risk of falling and to determine if this association is independent of balance. METHODS: Participants were 188 community-dwelling individuals aged 65 and older. All participants underwent baseline and annual evaluations with review of health history, standardized neurologic examination, neuropsychological testing, and qualitative and quantitative assessment of motor function. Falls were recorded prospectively using weekly online health forms. RESULTS: During 13 months of follow-up, there were 65 of 188 participants (34.6%) who reported at least one fall. Univariate analysis showed that fallers were more likely to have lower baseline scores in executive function than non-fallers (p = 0.03). Among participants without balance impairment we found that higher executive function z-scores were associated with lower fall counts (p = 0.03) after adjustment for age, sex, health status and prior history of falls using negative binomial regression models. This relationship was not present among participants with poor balance. CONCLUSIONS: Lower scores on executive function tests are a risk factor for falls in participants with minimal balance impairment. However, this effect is attenuated in individuals with poor balance where physical or more direct motor systems factors may play a greater role in fall risk.

Prevalence of complicated gastroesophageal reflux disease and Barrett's esophagus among racial groups in a multi-center consortium.

AIMS: The Clinical Outcomes Research Initiative database was used to evaluate ethnic trends in complicated reflux disease and suspected Barrett's esophagus among various racial groups. METHODS: Endoscopic findings for procedures performed January 2000-December 2005 for any indication and for reflux-related indications were reviewed by racial group. RESULTS: Of 280,075 procedures examined, Hispanics were the most likely to have esophagitis (Hispanic 19.6%, white 17.3%, black 15.8%, Asian/Pacific Islander 9.5%, P-value<0.0001), and white subjects were most likely to have suspected BE (white 5.0%, Hispanic 2.9%, Asian/Pacific Islander 1.8%, black 1.5%, P-value<0.0001). Endoscopies performed for reflux-related indications had similar trends for esophagitis and esophageal stricture. Among reflux/Barrett's screening procedures adjusted for age and gender, Hispanics were most likely to have esophagitis (OR=1.28, P-value<0.0001) compared to Caucasians. CONCLUSION: Our results demonstrate an association of suspected Barrett's esophagus and stricture with white patients and esophagitis with Hispanic patients. These findings need to be followed-up with further study.

The value of traditional upper endoscopy as a diagnostic test for Barrett's esophagus.

BACKGROUND: The standard test for diagnosing Barrett's esophagus (BE) is a conventional upper endoscopy. However, studies have shown that confirmation of BE by endoscopy with histologic intestinal metaplasia can be difficult. OBJECTIVE: To determine the overall accuracy, as well as factors that influence the accuracy of a conventional upper endoscopy in diagnosing BE. SETTING: Thirteen academic, community, and Veterans Affairs sites. DESIGN: A retrospective data review. PATIENTS: Patients who underwent an upper endoscopy with a finding of "suspected Barrett's esophagus" and esophageal biopsies. Pathology reports were examined to identify cases with intestinal metaplasia. MAIN OUTCOME MEASUREMENTS: Percentage of pathology-confirmed BE among suspected cases. RESULTS: A total of 2511 procedures were examined; the frequency of biopsy-confirmed BE was 48.4%. Multivariate logistic regression identified the following factors to be independently associated with biopsy-confirmed BE: long-segment BE that measured > or = 3 cm (odds ratio [OR] 4.61 [95% CI, 3.73-5.69]), male sex (OR 1.82 [95% CI, 1.49-2.22]), increasing age (age interval 70-79 years with OR 2.33 compared with age <50 years [95% CI, 1.75-3.10]), the presence of a hiatal hernia (OR 1.46 [95% CI, 1.22-1.84]), and white race (OR 1.90 [95% CI, 1.49-2.22]). LIMITATIONS: Biopsy specimens were assumed to sample the tubular esophagus; the actual pathology slides were not reevaluated by the investigators. CONCLUSIONS: Endoscopic evaluation has limitations for the diagnosis of BE. Specific patient and endoscopic characteristics may be associated with the confirmation of BE on biopsy specimens. Further study is needed to determine if new endoscopic imaging technologies improve the ability to correctly identify BE.

A phase I study of 5-fluorouracil, leucovorin, and celecoxib in patients with incurable colorectal cancer.

A phase I study of fixed-dose 5-fluorouracil (FU) and leucovorin (LCV), with excalating doses of the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib, was conducted in 16 patients with advanced colorectal adenocarcinoma. At doses typically used to treat arthritis patients (100-200 mg po BID), celecoxib did not increase toxicities expected from the chemotherapy alone. 5-FU and leucovorin did not affect COX-2 inhibition by celecoxib. Preliminary data suggest it is safe to combine celecoxib with standard chemotherapeutic agents, in treatment of patients with colorectal cancer.

Colonic biopsy practice for evaluation of diarrhea in patients with normal endoscopic findings: results from a national endoscopic database.

BACKGROUND: The colonic biopsy is the only reliable method for identification of microscopic colitis in patients with chronic diarrhea and normal endoscopic findings. METHODS: The Clinical Outcomes Research Initiative national endoscopic database was analyzed to determine the rate at which colonic biopsy specimens were obtained in patients undergoing colonoscopy for the evaluation of diarrhea with no visible mucosal abnormality. RESULTS: Between January 2000 and December 2003, 5565 unique adult patients underwent colonoscopy for evaluation of diarrhea without detection of any mucosal abnormality. Colonic mucosal biopsy specimens were obtained in 4410 (79.2%) of these patients. The rates at which biopsy specimens were obtained differed among the sites where colonoscopy was performed; biopsy specimens were obtained from more patients undergoing colonoscopy in university-affiliated settings (86.8%) compared with Veterans Affairs Medical Centers (VAMC) (78.5%) or community sites (78.6%) ( p < 0.001). On multivariate analysis, biopsy specimens were more likely to be obtained in younger patients (OR 0.7: 95%CI[0.6, 0.8] for age >50 years vs. <50 years), women patients (OR 1.4: 95% CI[1.2, 1.6] in community setting; OR 4.1: 95% CI[1.6, 10.5] in VAMC setting), and patients seen in university-affiliated medical centers (university center OR 2.1: 95% CI[1.5, 3.0] vs. community setting). CONCLUSIONS: Biopsy specimens are obtained in four fifths of patients with diarrhea and normal colonoscopy findings to exclude microscopic colitis. Variation in biopsy practice exists among endoscopy site types and by gender. Clear guidelines are needed for the endoscopic approach to these patients.