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Context In previous SURPASS studies tirzepatide reduced hemoglobin glycated A1c (HbA1c) and body weight and improved markers of insulin sensitivity and β-cell function to a greater extent than comparators. Objective Explore changes in biomarkers of β-cell function and insulin sensitivity and in efficacy profiles in baseline biomarker quartile analyses with tirzepatide compared to semaglutide. Design Post hoc analysis of SURPASS-2 phase 3 trial (participants randomly assigned to receive weekly subcutaneous tirzepatide or semaglutide for 40 weeks). Setting Post hoc analysis of 128 sites in 8 countries. Participants A total of 1879 participants with type 2 diabetes. Interventions Once-weekly tirzepatide (5, 10, 15 mg) or semaglutide 1 mg. Main outcomes measures Change in homeostatic model assessment indices for pancreatic β-cell function (HOMA2-B) and for insulin resistance (HOMA2-IR), fasting glucagon, fasting C-peptide, and fasting insulin. Results At week 40, a greater increase in HOMA2-B was seen with tirzepatide (5, 10, 15 mg) doses (96.9-120.4%) than with semaglutide 1 mg (84.0%) (P <.05). There was a greater reduction in HOMA2-IR with all doses of tirzepatide (15.5%-24.0%) than with semaglutide 1 mg (5.1%) (P <.05). Tirzepatide 10 and 15 mg resulted in a significant reduction in both fasting C-peptide (5.2%-6.0%) and fasting glucagon (53.0%-55.3%) compared with an increase of C–peptide (3.3%) and a reduction of glucagon (47.7%) with semaglutide 1 mg (P <.05). HbA1c and body weight reductions were greater with all tirzepatide doses than semaglutide within each HOMA2-B and HOMA2-IR baseline quartile. Conclusion In this post hoc analysis, improvements in HbA1c and weight loss were consistent and significantly higher with tirzepatide, regardless of baseline β-cell function and insulin resistance, compared with semaglutide. [ABSTRACT FROM AUTHOR]

The Winam Gulf (Kenya) is frequently impaired by cyanobacterial harmful algal blooms (cHABs) due to inadequate wastewater treatment and excess agricultural nutrient input. While phytoplankton in Lake Victoria have been characterized using morphological criteria, our aim is to identify potential toxin‐producing cyanobacteria using molecular approaches. The Gulf was sampled over two successive summer seasons, and 16S and 18S ribosomal RNA gene sequencing was performed. Additionally, key genes involved in production of cyanotoxins were examined by quantitative PCR. Bacterial communities were spatially variable, forming distinct clusters in line with regions of the Gulf. Taxa associated with diazotrophy were dominant near Homa Bay. On the eastern side, samples exhibited elevated cyrA abundances, indicating genetic capability of cylindrospermopsin synthesis. Indeed, near the Nyando River mouth in 2022, cyrA exceeded 10 million copies L−1 where there were more than 6000 Cylindrospermopsis spp. cells mL−1. In contrast, the southwestern region had elevated mcyE gene (microcystin synthesis) detections near Homa Bay where Microcystis and Dolichospermum spp. were observed. These findings show that within a relatively small embayment, composition and toxin synthesis potential of cHABs can vary dramatically. This underscores the need for multifaceted management approaches and frequent cyanotoxin monitoring to reduce human health impacts. [ABSTRACT FROM AUTHOR]

AbstractObjective: Multitasking is an essential part of everyday functioning often not formally assessed by traditional neuropsychological tests. Although individuals with Parkinson’s disease (PD) experience both motor and cognitive difficulties, previous research has demonstrated more pronounced functional difficulties with the presence of mild cognitive impairment (PD-MCI). The current study compared individuals with PD-MCI, PD with normal cognition (PD-NC), and healthy controls on a naturalistic task of multitasking, the Day Out Task (DOT). Method: Participants were 38 healthy older adults (HOA), 23 individuals with PD-NC, and 15 individuals with PD-MCI. Participants completed a battery of neuropsychological tasks and the DOT. Informants also completed a self-reported questionnaire of participants’ everyday executive functioning. Results: Compared to PD-NC and HOA, participants with PD-MCI were less accurate and efficient and took longer to complete the DOT. After controlling for motor performance, only DOT accuracy remained worse, with poorer accuracy resulted from more subtasks being left incomplete or being completed inaccurately by the PD-MCI group. DOT sequencing was a significant predictor of informant reported everyday dysexecutive symptoms. Conclusions: The findings highlight that individuals with PD-MCI are likely to experience difficulties completing complex everyday tasks due to both motor and cognitive impairments. Clinicians may therefore recommend strategies to support efficiency and accuracy in complex tasks of everyday functioning in treatment considerations. [ABSTRACT FROM AUTHOR]

Objective Traditional measures of cognitive abilities most used by neuropsychologists are generally low in ecological validity and only capture a small proportion of the variance of a person's true functional capacity. This study evaluates the association between clinic-based performance and parallel real-world completion of an everyday planning test, the Overnight Trip Task (OTT). Method A cross-sectional cohort of 65 community-dwelling older adults completed a battery of cognitive assessments and two formats of the OTT: the paper-and-pencil clinic OTT, which was completed remotely through video conferencing (Zoom), and the parallel real-world OTT (RW-OTT), which was completed at home between sessions. Both formats required participants to plan for what they would pack and prepare for a hypothetical overnight trip based on a provided story that included rules and embedded contingencies. Results The clinic OTT demonstrated a small-to-moderate relationship with the RW-OTT (r  = 0.35) and no relationship with measures of learning, long delay recall, an executive function composite, and a measure of everyday planning. Hierarchical regressions indicated that the clinic OTT demonstrated incremental validity above an executive function composite measure and global cognition when predicting self-reported everyday functioning and RW-OTT performance. Conclusions The clinic OTT showed only modest association with the RW-OTT and discriminate but not convergent validity was demonstrated. The clinic OTT showed incremental validity when predicting self-reported everyday functioning and RW-OTT performance above more traditional measures. Before the clinic OTT could be considered a reliable and valid clinic-based measure for predicting real-world behavior, additional research would be needed. [ABSTRACT FROM AUTHOR]

Context Antidrug antibodies (ADA) can potentially affect drug pharmacokinetics, safety, and efficacy. Objective This work aimed to evaluate treatment-emergent (TE) ADA in tirzepatide (TZP)-treated participants across 7 phase 3 trials and their potential effect on pharmacokinetics, efficacy, and safety. Methods ADA were assessed at baseline and throughout the study until end point, defined as week 40 (SURPASS-1, -2, and -5) or week 52 (SURPASS-3, -4, Japan-Mono, and Japan-Combo). Samples for ADA characterization were collected at SURPASS trial sites. Participants included ADA-evaluable TZP-treated patients with type 2 diabetes (N = 5025). Interventions included TZP 5, 10, or 15 mg. ADA were detected and characterized for their ability to cross-react with native glucose-dependent insulinotropic polypeptide (nGIP) and glucagon-like peptide-1 (nGLP-1), neutralize tirzepatide activity on GIP and GLP-1 receptors, and neutralize nGIP and nGLP-1. Results TE ADA developed in 51.1% of tirzepatide-treated patients. Proportions were similar across dose groups. Maximum ADA titers ranged from 1:20 to 1: 81 920 among TE ADA+ patients. Neutralizing antibodies (NAb) against TZP activity on GIP and GLP-1 receptors were observed in 1.9% and 2.1% of patients, respectively. Less than 1.0% of patients had cross-reactive NAb against nGIP or nGLP-1. TE ADA status, ADA titer, and NAb status had no effect on the pharmacokinetics or efficacy of TZP. More TE ADA+ patients experienced hypersensitivity reactions or injection site reactions than TE ADA– patients. The majority of hypersensitivity and injection site reactions were nonserious and nonsevere, and most events occurred and/or resolved irrespective of TE ADA status or titer. Conclusion Immunogenicity did not affect TZP pharmacokinetics or efficacy. The majority of hypersensitivity or injection site reactions experienced by TE ADA+ patients were mild to moderate in severity. [ABSTRACT FROM AUTHOR]

Wearing a cloth face mask has been shown to impair exercise performance; it is essential to understand the impact wearing a cloth face mask may have on cognitive performance. Participants completed two maximal cardiopulmonary exercise tests on a cycle ergometer (with and without a cloth face mask) with a concurrent cognitive task. Blood pressure, heart rate, oxygen saturation, perceived exertion, shortness of breath, accuracy, and reaction time were measured at rest, during each exercise stage, and following a 4-minute recovery period. The final sample included 35 adults (age = 26.1 ± 5.8 years; 12 female/23 male). Wearing a cloth face mask was associated with significant decreases in exercise duration (−2:00 ± 3:40 min, P = 0.003), peak measures of maximal oxygen uptake (−818.9 ± 473.3 mL/min, −19.0 ± 48 mL·min-1·kg-1, P < 0.001), respiratory exchange ratio (−0.04 ± 0.08, P = 0.005), minute ventilation (−36.9 ± 18 L/min), oxygen pulse (−3.9 ± 2.3, P < 0.001), heart rate (−7.9 ± 12.6 bpm, P < 0.001), oxygen saturation (−1.5 ± 2.8%, P = 0.004), and blood lactate (−1.7 ± 2.5 mmol/L, P < 0.001). While wearing a cloth face mask significantly impaired exercise performance during maximal exercise testing, cognitive performance was unaffected in this selected group of young, active adults. [ABSTRACT FROM AUTHOR]

Purpose: To quantify the preferences of people with type 2 diabetes (T2D) for treatment attributes of a glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist (RA) versus an injectable GLP-1 RA medication profile. Patients and Methods: Injection-naive people taking oral medications for T2D in the US and UK completed a web survey including a discrete choice experiment to quantify patients' preferences for five treatment attributes: delivery system, frequency of nausea, frequency of hypoglycemia, HbA1c reduction, and weight reduction. Attributes and levels were based on head-to-head clinical trial data of tirzepatide 5mg, 10mg, and 15mg versus semaglutide 1mg. Preference data were analyzed separately by country using multinomial mixed logit (MXL) models. MXL parameters were used to estimate the predicted preference for each tirzepatide dose versus semaglutide 1mg. Direct preferences for each dose of tirzepatide versus semaglutide 1mg were elicited. Results: Participants (N=620) in the US (N=301) and UK (N=319) were 50.8% and 50.5% female with mean ages of 60.7 years and 58.9 years, respectively. The order and magnitude of relative attribute importance (RAI) scores differed between countries. HbA1c reduction (26.3%) had the greatest impact on US participants' preferences, and hypoglycemia (32.8%) did among UK participants. Attribute-level marginal utility results indicated preferences for greater HbA1c improvements, the single-use pre-filled pen, lower hypoglycemia, greater weight reductions, and lower frequency of nausea. Assuming the availability of only tirzepatide or semaglutide 1mg, the predicted preference for tirzepatide (5, 10, and 15mg) in the US is 95.6% (vs 4.4% for semaglutide 1mg) and in the UK was 86.3% (vs 13.7% for semaglutide 1mg). Conclusion: HbA1c reduction, frequency of hypoglycemia, and weight reduction are key drivers of preferences among people with T2D when considering medication options. Overall, people with T2D are likely to prefer the tirzepatide over the semaglutide 1mg medication profiles. [ABSTRACT FROM AUTHOR]

A 23-year-old male competitive athlete performed a maximal cardiopulmonary exercise test on a cycle ergometer with a concurrent cognitive test on an iPad 6 days before and 19 weeks after a nonhospitalized COVID-19 illness. Results indicated reductions in time to exhaustion (−3.25 min), peak oxygen consumption (–1.68 mL/kg/min), and accuracy (–8%) during peak exertion despite his return to prior levels of activity. Reductions in functional or cognitive performance in competitive athletes may elicit noticeable differences in athletic performance; therefore, fitness specialists should consider the assessment of both cognitive function as well as aerobic capacity in athletes following COVID-19, regardless of severity, to facilitate safe and effective return to activity. [ABSTRACT FROM AUTHOR]

Objectives: To (1) determine if wearing a cloth face mask significantly affected exercise performance and associated physiological responses, and (2) describe perceptual measures of effort and participants' experiences while wearing a face mask during a maximal treadmill test.Methods: Randomised controlled trial of healthy adults aged 18-29 years. Participants completed two (with and without a cloth face mask) maximal cardiopulmonary exercise tests (CPETs) on a treadmill following the Bruce protocol. Blood pressure, heart rate, oxygen saturation, exertion and shortness of breath were measured. Descriptive data and physical activity history were collected pretrial; perceptions of wearing face masks and experiential data were gathered immediately following the masked trial.Results: The final sample included 31 adults (age=23.2±3.1 years; 14 women/17 men). Data indicated that wearing a cloth face mask led to a significant reduction in exercise time (-01:39±01:19 min/sec, p<0.001), maximal oxygen consumption (VO2max) (-818±552 mL/min, p<0.001), minute ventilation (-45.2±20.3 L/min), maximal heart rate (-8.4±17.0 beats per minute, p<0.01) and increased dyspnoea (1.7±2.9, p<0.001). Our data also suggest that differences in SpO2 and rating of perceived exertion existed between the different stages of the CPET as participant's exercise intensity increased. No significant differences were found between conditions after the 7-minute recovery period.Conclusion: Cloth face masks led to a 14% reduction in exercise time and 29% decrease in VO2max, attributed to perceived discomfort associated with mask-wearing. Compared with no mask, participants reported feeling increasingly short of breath and claustrophobic at higher exercise intensities while wearing a cloth face mask. Coaches, trainers and athletes should consider modifying the frequency, intensity, time and type of exercise when wearing a cloth face mask. [ABSTRACT FROM AUTHOR]

Background: Compensatory aids can help mitigate the impact of progressive cognitive impairment on daily living.Objective: We evaluate whether the learning and sustained use of an Electronic Memory and Management Aid (EMMA) application can be augmented through a partnership with real-time, activity-aware transition-based prompting delivered by a smart home.Methods: Thirty-two adults who met criteria for amnestic mild cognitive impairment (aMCI) were randomized to learn to use the EMMA app on its own (N = 17) or when partnered with smart home prompting (N = 15). The four-week, five-session manualized EMMA training was conducted individually in participant homes by trained clinicians. Monthly questionnaires were completed by phone with trained personnel blind to study hypotheses. EMMA data metrics were collected continuously for four months. For the partnered condition, activity-aware prompting was on during training and post-training months 1 and 3, and off during post-training month 2.Results: The analyzed aMCI sample included 15 EMMA-only and 14 partnered. Compared to the EMMA-only condition, by week four of training, participants in the partnered condition were engaging with EMMA more times daily and using more basic and advanced features. These advantages were maintained throughout the post-training phase with less loss of EMMA app use over time. There was little differential impact of the intervention on self-report primary (everyday functioning, quality of life) and secondary (coping, satisfaction with life) outcomes.Conclusion: Activity-aware prompting technology enhanced acquisition, habit formation and long-term use of a digital device by individuals with aMCI. (ClinicalTrials.gov NCT03453554). [ABSTRACT FROM AUTHOR]

Following a traumatic coronary artery dissection and subsequent myocardial infarction from a nonpenetrating strike to the chest by an airborne metal pipe, a 33-year-old male police officer completed 12 weeks of high-intensity, symptom-limited cardiac rehabilitation in order to return to active duty. Physiological and perceptual responses to exercise were used to progress the patient through high-intensity activities that challenged the musculoskeletal and cardiorespiratory systems while simulating real work activities. In addition to substantial improvements in functional capacity (8.6 to 10.3 METS) and left ventricular ejection fraction (20% to 45%), the patient was able to fully return to work as an active-duty police officer. [ABSTRACT FROM AUTHOR]

There is currently a need to identify feasible and effective interventions to help older individuals suffering from memory loss maintain functional independence and quality of life. To improve upon paper and pencil memory notebook interventions, the Digital Memory Notebook (DMN) application (app) was developed iteratively with persons with cognitive impairment. In this paper we detail a manual-based intervention for training use of the DMN app. A series of three case studies are described to illustrate the clinical process of the DMN intervention, the key components of the intervention and participants' perceptions of the intervention. The Reliable Change Index was applied to pre/post intervention scores that examined everyday memory lapses, daily functioning, coping self-efficacy, satisfaction with life, and quality of life with standardized measures. Following the intervention, two of three participants self-reported a clinically significant reduction in everyday memory lapses and improved everyday functioning. One participant reported clinically significant change in quality of life. All participants demonstrated clinically significant changes in their ability to cope with problems and build self-efficacy. Furthermore, all participants scored in the normative range post-intervention on the measure of satisfaction with life. Clinical observations and participant feedback were used for refinement of the DMN intervention (ClinicalTrials.gov NCT03453554). [ABSTRACT FROM AUTHOR]

A 29-year-old woman with a left ventricular assist device (LVAD) completed a progressive, symptom-limited cardiac rehabilitation program consisting of boxing, weight-lifting, and aerobic exercise, where she improved her exercise capacity by 2.7 metabolic equivalents (P < 0.001) and demonstrated significant myocardial recovery, allowing for successful LVAD explant 9 months after implantation. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the maximum rate-pressure product of cardiac rehabilitation participants after myocardial infarction, percutaneous coronary intervention, or both during high-intensity resistance training (HI-RT) using continuous blood pressure monitoring. Thirty-four individuals exercised on the leg press machine while being monitored with a continuous blood pressure monitor. The maximum rate-pressure product was significantly lower than the established safety threshold of 36,000 (P < 0.001), with a mean of 17,369 and standard deviation of 6634. Only 2% of observations had a value ≥36,000. These results suggest that cardiac rehabilitation patients can perform HI-RT while keeping their rate-pressure products under the safety threshold of 36,000 after myocardial infarction/percutaneous coronary intervention. Performance of HI-RT exercises contributes to return to precardiac event occupations, and continuous blood pressure monitoring may be an effective tool in evaluating the safety of HI-RT in this patient population. [ABSTRACT FROM AUTHOR]

Purpose: Memory impairment can necessitate use of external memory aids to preserve functional independence. As external aids can be difficult to learn and remember to use, technology may improve the efficacy of current rehabilitation strategies. We detail the iterative development of a digital application of a paper-and-pencil memory notebook. Methods: Twenty participants (aged 54+) of varying levels of cognitive ability were recruited for four iterations of usability testing (five participants per iteration). Each participant completed a series of tasks using the digital memory notebook (DMN), followed by questionnaires that assessed satisfaction (Questionnaire for User Interface Satisfaction) and usability ratings (Post-Study System Usability Questionnaire) for the application. Results and Conclusions: Between Iterations 2 and 5, participants demonstrated marked reductions in time to complete several types of tasks (e.g., add event, navigate interface) using the DMN. Participants in Iteration 5 also rated all subscales of both the usability and satisfaction questionnaires very highly. Faster task completion times were correlated with more favourable system ratings. However, neither task performance times nor system ratings were correlated with cognitive abilities, scheduling tool use or comfort with technology. Both the questionnaire and performance-based data indicate the final iteration of the DMN was easy to use. Furthermore, the application was user-friendly despite individual differences in cognitive ability, familiarity with scheduling tools and comfort with technology. Future work will demonstrate whether the DMN will support everyday retrospective and prospective memory lapses and increase the functional independence and quality of life for persons with cognitive impairment. Building on practice standards and user-centred design, the digital memory notebook (DMN) application is an "all-in-one" memory aid and organizational tool with an intuitive interface designed to help improve everyday functioning. The DMN's today page, to do list and calendar functions can support everyday prospective and retrospective memory abilities. The DMN's notes, journaling and motivational functions can support longer-term goal planning and mood management. The DMN's alarm functions can support learning to use the DMN and serve as reminders to support prospective memory and aid in activity completion. [ABSTRACT FROM AUTHOR]

Objective: Planning, a higher order executive functioning ability important for accomplishing complex everyday tasks, can be differentiated into initial and concurrent (online) planning. In this study, initial plans were codified to assess their impact on task execution. Cognitive correlates of initial planning and task execution were also examined. Method: One-hundred fifty-four community dwelling older adults completed a naturalistic task, called the Day Out Task (DOT), in either a planning or no planning condition. The DOT required participants to multitask and efficiently complete a series of eight subtasks, preparing for a hypothetical day out. Participants also completed a neuropsychological battery with the following cognitive constructs assessed: processing speed, cognitive flexibility, episodic memory, visuoconstructional abilities, and working memory and sequencing. Results: There were no significant differences between the planning and no planning conditions in DOT execution accuracy, efficiency or duration. However, efficiency of the initial plan was a significant predictor of task execution efficiency and initial plans that contained a higher amount of Task Relevant Associations predicted a shorter duration of task execution after controlling for age, processing speed and episodic memory. Furthermore, initial plans that had more Task Relevant Associations and task executions that took less time were associated with better working memory and sequencing ability. Discussion: Quality of the initial plan is important. Initial plans that organize task objectives in an efficient manner may lead to better task execution efficiency, while initial plans that demonstrate a detailed understanding of individual relational aspects of the tasks (i.e., higher rate of Task Relevant Associations) may result in faster task execution. [ABSTRACT FROM AUTHOR]

A 56-year-old man with end-stage heart failure performed a 4-week, symptom-limited, progressive inpatient cardiac prehabilitation program while confined to the cardiovascular intensive care unit awaiting heart transplantation. Mobility was limited by an acute gout flare and multiple central venous access lines. He received a tailored prescription of intermittent boxing, supervised hallway ambulation, stair training, and golfing on a putting green on four consecutive weekdays and was encouraged to mobilize with nursing on the remaining days. The patient progressed and by the last week demonstrated increased activity tolerance. He had a successful transplant after 40 days in the intensive care unit and was discharged with stamina sufficient to participate in outpatient cardiac rehabilitation, demonstrating the value, safety, and feasibility of an individualized inpatient cardiac prehabilitation program for patients with advanced cardiac disease medically confined to the intensive care unit. [ABSTRACT FROM AUTHOR]

A 53-year-old male mountain biker received a total artificial heart and remained in the cardiovascular intensive care unit for 56 days. To reduce functional decline caused by inactivity, he performed a six-session cycle ergometer exercise program in his hospital room. Traditional cardiac responses for exercise prescription were not applicable; therefore, a symptom-limited, monitored progression scheme in conjunction with recommendations for the artificial heart was implemented to modify duration and intensity. Over the six sessions, the patient improved his distance pedaled by 320% and functional capacity by 1 metabolic equivalent. He was subsequently discharged from the hospital and later successfully transplanted without readmission. [ABSTRACT FROM AUTHOR]

A 53-year-old female athlete with spontaneous coronary artery dissection, acute myocardial infarction, and infrarenal abdominal aortic dissection enrolled in a 6-week cardiovascular rehabilitation (CR) program. During CR sessions, the patient performed a combination of aerobic, resistance training, and core activities. In the final CR session, the patient performed reflex activities and the forced Valsalva maneuver. The patient's electrocardiogram, blood pressure, heart rate, and transient change in blood pressure over time were continuously monitored and recorded. The patient completed CR without negative symptoms or adverse events. [ABSTRACT FROM AUTHOR]

To describe the clinical implications of wearing a mask among special populations in inpatient rehabilitation. Narrative Review. Inpatient rehabilitation. Patients undergoing acute inpatient rehabilitation. Mask wearing. Effect of mask wearing on exercise outcomes, including perceived exertion, shortness of breath, and patient perception; clinical implications for the interdisciplinary team. Five trials which observed exercise outcomes after mask wearing were identified and summarized. Findings for the effect of face masks on exercise and vital signs varied due to heterogeneity of exercise protocols and outcome measures. Relevant findings show that patients who wore masks had higher ratings of perceived exertion, increased shortness of breath, and feelings of claustrophobia while wearing a face mask during exercise. Wearing masks affected physical and mental outcomes despite exercise intensity (low, moderate, or high). Moderate-to-high intensity exercise is needed for neuroplasticity. This type of exercise may not be possible in neurological populations, who do not have normal oxygen consumption at rest or with exercise, and may be further affected by wearing masks. Clinicians should their patients' mask wearing into consideration, and change the frequency, intensity, timing and types of exercises when patients are wearing a face mask. Frequent measurement of vital signs and fatigue symptoms are critical to maintain patient safety, and adjustments should be made as necessary. Other neurological challenges to monitor include impaired cognitive function, limited communication, reduced mood, and interactions with medications. These can affect the patients' ability to accurately determine and state their perceived effort or may hinder physiological and autonomic responses. Lastly, interdisciplinary teams should communicate patient findings related to mask wearing at team conferences, huddles and include discussion for ways to increase patients' participation and how to optimize health outcomes. None. [ABSTRACT FROM AUTHOR]

The Cognistat is a widely used neurobehavioral screening instrument that addresses functioning across multiple domains. Unlike many popular neuropsychological tests, the Cognistat does not currently assess learning efficiency for verbal material. The purpose of this study was to develop a screening method for assessing verbal learning efficiency with the Cognistat, investigate the effects of two demographic variables (age and gender) on performance, and to establish cutoff scores for impairment. Participants were 253 volunteers between the ages of 18 and 96 years. Participants were classified into two age groups: 18-64 years and 65 + years. The data revealed a significant age and gender performance difference. Implications for the present findings and for future research are presented. [ABSTRACT FROM AUTHOR]

Background: Advances in technology have fueled new opportunities to improve external compensatory devices. The Digital Memory Notebook (DMN) is an iOS tablet application (app) developed in collaboration with older individuals with mild cognitive impairment (MCI) to support functional independence. To understand users for whom DMN training was beneficial, we examined data from a pilot clinical trial for factors that influenced sustained use of this compensatory tool. Method: Twenty‐five participants (M age = 72; M education = 16; 48% female) with MCI learned to use the DMN app in 5‐6 (two‐hour) training sessions delivered within one‐month. Participant use of the DMN app was then monitored through real‐time collection of data usage metrics for an additional three months. Based on app use during the third‐month post‐training, participants were divided into DMN user (N = 13; M daily distinct uses = 4.5) and non‐user (N = 12) groups. Demographics, clinician ratings, baseline clinical measures and DMN usage metrics were all examined. Result: No group differences emerged in demographics, pre‐morbid ability estimate (High Average), or clinician ratings of motivation, comprehension, insight and competency during training sessions. DMN non‐users exhibited lower scores on standardized measures of global cognitive status (Low Average vs. Average) and memory (Borderline vs. Low Average), and self‐reported poorer everyday memory. DMN usage metrics captured during training revealed no group differences in week one (sessions 1‐2). By week two (session 3), DMN non‐users showed fewer daily distinct uses of the DMN (4 vs. 8). During weeks 3 and 4, DMN non‐users continued to show fewer daily distinct uses as well as fewer interactions with all sections of the app (i.e., calendar, daily event scheduling, notes and journal). Non‐users also demonstrated poorer use of advanced app functions during training (e.g., high priority scheduling, reminder alarms, picture use, prospective memory use). Conclusion: Individuals with MCI who were actively using the DMN three‐months post‐intervention were less cognitively impaired, demonstrated greater DMN use as early as week two of training, and made use of advanced functions. Next steps include increasing DMN use through early adaptive learning and continued automated booster training. [ABSTRACT FROM AUTHOR]

The Cognistat is a widely used screening instrument for assessing cognitive functioning. However, the manualized scoring guidelines for one of the questions in the Judgment subtest appear insensitive to responses when examinees answer in light of current societal attitudes. Penalization of examinees is likely to lead to an underestimation of functional ability and a decrease in test validity. Suggestions for correcting this issue are presented. [ABSTRACT FROM AUTHOR]

Background: Cognitive changes experienced by individuals with mild cognitive impairment (MCI) can impact everyday functioning and lower self‐confidence. The Electronic Memory and Management Aid (EMMA) is a senior‐friendly iOS tablet application designed to support everyday activities. To examine whether learning and sustained app use could be improved, we partnered EMMA with a smart home that delivered activity‐aware prompting. Method: In a pilot trial, participants with MCI were randomly assigned to learn to use EMMA with (N = 14; M age = 74) or without (N = 15; M age = 71) smart home prompting. Training consisted of 5‐6 (two‐hour) structured sessions delivered in a 4‐week timeframe by a clinician in the participant's home (half turned into smart homes). Real‐time data were collected on participant use of EMMA, with metrics averaged across these intervals: weeks 1‐2 (early‐training), 5‐6 (post‐training), 10‐11 (prompting turned off) and 15‐16 (follow‐up; prompting back on). Baseline, post‐training and follow‐up clinical data (coping, life satisfaction, everyday functioning) were also compared. Result: No group differences emerged in age, education, estimated pre‐morbid ability (High Average), memory (Low Average) or executive functioning (Average). Participants in the partnered condition engaged daily with EMMA more times post‐training (M = 5.0) compared to the control (not‐partnered) condition (M = 2.0). Participants in the partnered condition also maintained a high level of engagement with EMMA even after prompting stopped (M = 5.0, M = 3.8 at follow‐up). This contrasted with significantly lowered use (M = 1.2 and M = 0.6, respectively) in the control condition. Similar patterns were found for usage rates of app components (event scheduling, calendar use) and advanced features (searches, alarms, pictures). Clinical data showed self‐reported positive changes in coping and life satisfaction that did not differ by condition; no significant changes were self‐reported in everyday functioning. Conclusion: Partnering EMMA with a smart home that cued app use at opportune times and after periods of non‐use improved habit formation and earlier mastery of the tool. Once a habit was established, turning off the prompts did not impact use of the EMMA app, demonstrating the importance of habit formation and early mastery to sustain tool use. [ABSTRACT FROM AUTHOR]

The novel dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist tirzepatide (TZP) is in development for type 2 diabetes (T2D). Efficacy and safety of once weekly TZP vs. semaglutide (SEMA) was assessed in people with T2D on background metformin. In this open-label, 40-wk Phase 3 study, people with T2D (N=1879; mean baseline [BL] HbA1c 8.28%; age 56.6 y; T2D duration 8.6 y; BMI 34.2 kg/m2) were randomized (1:1:1:1) to TZP (5, 10, 15 mg) or SEMA (1 mg). Primary efficacy objective was noninferiority of TZP 10 and/or 15 mg vs. SEMA for mean change in HbA1c from BL at 40 wk. Secondary objectives included noninferiority (TZP 5 mg) for HbA1c change and superiority (all TZP doses) for change in HbA1c, body weight (BW) and fasting serum glucose (FSG), and proportion of patients with HbA1c <7%, ≤6.5% and <5.7% (except TZP 5 mg) and BW loss ≥5%, ≥10%, ≥15% at 40 wk. All TZP doses were superior to SEMA for change from BL in mean HbA1c, FSG, BW and in achieving all HbA1c and BW loss targets at 40 wk (Table). The most common AEs were gastrointestinal and mostly mild to moderate in severity. Clinically significant (blood glucose <54 mg/dL) or severe hypoglycemia events were low. In conclusion, all TZP doses demonstrated superior and clinically meaningful improvement in glycemic control and substantial weight loss vs. SEMA 1 mg in people with T2D treated with metformin. Disclosure: J. Frias: Consultant; Self; 89bio, Inc., Altimmune, Axcella Health Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk, Pfizer Inc., Sanofi, Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, CymaBay Therapeutics, Eli Lilly and Company, Intercept Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Pfizer Inc., Sanofi, Speaker's Bureau; Self; Merck & Co., Inc., Sanofi. M. J. Davies: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Boehringer Ingelheim Limited (UK), Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., Novo Nordisk A/S, Sanofi, Other Relationship; Self; AstraZeneca, NIHR Leicester Biomedical Research Centre, Novo Nordisk, Speaker's Bureau; Self; Astra Zeneca Pharma India Ltd, Boehringer Ingelheim (China), Boehringer Ingelheim (Philippines), Inc., Boehringer Ingelheim International GmbH, Boehringer Ingelheim Limited (UK), Boehringer Ingelheim Saudi Arabia Trading, Boehringer Ingelheim Singapore Pte. Ltd, Boehringer Ingelheim Sp. Z o. o., Eli Lilly and Company, Napp Pharmaceuticals, Novo Nordisk, Novo Nordisk A/S, S. C. Sanofi Romania SRL, Sanofi K. K. J. Rosenstock: Board Member; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Inc., Sanofi, Consultant; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Inc., Sanofi, Research Support; Self; Applied Therapeutics, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Genentech, Inc., Intarcia Therapeutics, Inc., Lexicon Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Oramed Pharmaceuticals, Inc., Pfizer Inc., REMD Biotherapeutics, Sanofi. F. C. Perez manghi: None. L. Fernandez lando: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. B. Bergman: Employee; Self; Eli Lilly and Company, Employee; Spouse/Partner; Eli Lilly and Company. B. Liu: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. X. Cui: Employee; Self; Eli Lilly and Company. K. Brown: Employee; Self; Eli Lilly and Company. Funding: Eli Lilly and Company [ABSTRACT FROM AUTHOR]

Tirzepatide (TZP) is a novel dual GIP/GLP-1 receptor agonist under development for the treatment of type 2 diabetes (T2D). The efficacy and safety of TZP vs. titrated insulin degludec (IDeg) were assessed in insulin-naïve patients with T2D inadequately controlled on metformin with/without SGLT-2i. In this open-label, 52-week, Phase 3 study, 1444 patients with T2D were randomized (1:1:1:1) to once-weekly TZP (5, 10, 15 mg) or once-daily IDeg (mean baseline [BL] age, 57.4 years; T2D duration, 8.4 years; HbA1c, 8.17%; BMI, 33.5 kg/m2; 32% on SGLT-2i). The primary efficacy endpoint was mean change in HbA1c from BL to Week 52. Secondary efficacy endpoints included mean change in fasting serum glucose (FSG) and body weight (BW) and proportion of subjects achieving HbA1c and BW goals. All TZP doses were superior to IDeg in mean change from BL in HbA1c and BW, and in the proportion of patients achieving all HbA1c and BW goals at Week 52 (Table). Among patients taking TZP 15 mg, 48.4% achieved HbA1c <5.7% and 42.5% achieved ≥15% BW loss. The most common AEs in TZP-treated patients were mild to moderate gastrointestinal events. Hypoglycemia incidence (<54 mg/dL or severe) was lower in all TZP arms vs. IDeg. In patients with T2D, TZP demonstrated clinically meaningful reductions in HbA1c and BW that were significantly greater vs. titrated IDeg at Week 52 with lower incidence of hypoglycemia. Disclosure: B. Ludvik: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Research Support; Self; Amgen Inc., Eli Lilly and Company, Novo Nordisk, Speaker's Bureau; Self; MSD Corporation. F. Giorgino: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Novo Nordisk, Roche Diabetes Care, Sanofi, Research Support; Self; Lilly Diabetes, Roche Diabetes Care. E. Jodar: Other Relationship; Self; AstraZeneca, Lilly Diabetes, Mundipharma International, Novo Nordisk, Speaker's Bureau; Self; Boehringer Ingelheim International GmbH. J. Frias: Consultant; Self; 89bio, Inc., Altimmune, Axcella Health Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk, Pfizer Inc., Sanofi, Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, CymaBay Therapeutics, Eli Lilly and Company, Intercept Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Pfizer Inc., Sanofi, Speaker's Bureau; Self; Merck & Co., Inc., Sanofi. L. Fernandez lando: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. K. Brown: Employee; Self; Eli Lilly and Company. R. Bray: None. Á. Rodríguez: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. Funding: Eli Lilly and Company [ABSTRACT FROM AUTHOR]