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BackgroundRecruitment to dementia prevention clinical trials is challenging, and participants are not representative of US adults at risk. A better understanding of the general public's interest in dementia prevention research participation is needed to inform future recruitment strategies.ObjectiveTo examine US adults' characteristics associated with self-reported likelihood to participate in dementia prevention clinical trials.DesignWe conducted a cross-sectional survey using the October 2018 wave of the University of Michigan National Poll on Healthy Aging.SettingThe National Poll on Healthy Aging is a nationally representative survey of adults using KnowledgePanel (Ipsos Public Affairs LLC), a probability-based panel of the civilian, noninstitutionalized US population.ParticipantsWe analyzed data from 1,028 respondents, ages 50 to 64 years, who completed a web survey module on brain health.MeasurementsWe used logistic regression models to examine associations between sociodemographic and dementia-related factors (e.g., family history) and self-reported likelihood to participate in a dementia prevention clinical trial of a new medicine ("very" or "somewhat likely" vs. "not likely" survey responses). Among respondents not likely to participate, we examined frequency of reasons endorsed for this decision, stratified by age, sex, and race and ethnicity.ResultsOf the 1,028 respondents, half were female, 68% Non-Hispanic White, 13% Hispanic, and 12% Non-Hispanic Black. Twelve percent of respondents reported being very likely to participate in a dementia prevention trial, 32% somewhat likely, and 56% not likely. Factors associated with higher likelihood to participate were higher perceived risk of dementia [OR, 2.17 (95% CI, 1.61, 2.93)], a positive family history of dementia [OR, 1.75 (95% CI, 1.27, 2.43)], and having discussed dementia prevention with a doctor [OR, 2.20 (95% CI, 1.10, 4.42)]. There were no differences in likelihood to participate by sociodemographic characteristics. Among 570 respondents not likely to participate, 39% said they did not want to be a guinea pig, 23% thought dementia would not affect them, 22% thought there would be too high a chance for harm, 15% indicated study participation would take too much time, and 5% reported fear of learning information about oneself. There were no differences across age, sex, and racial and ethnic groups.ConclusionsIn this study, perceived risk of dementia, family history, and discussion of prevention with a doctor were associated with likelihood to participate in a dementia prevention clinical trial, whereas sociodemographic factors including race and ethnicity were not. Findings suggest that recruitment interventions focused on increasing knowledge of dementia risk and prevention trials and involving healthcare providers may be effective tools to improve enrollment rates, regardless of target community.

Author(s): Amanda R. Mathew [sup.1] , Elizabeth F. Avery [sup.1] , Chelsea Cox [sup.2] , Patrick Nwanah [sup.1] , Ravi Kalhan [sup.3] , Brian Hitsman [sup.3] , Lynda H. Powell [...], Objective Smoking cessation for individuals with Chronic Obstructive Pulmonary Disease (COPD) is medically critical, but smoking for coping motives is a common barrier. Method In this evaluation of three treatment components (Mindfulness, Practice Quitting, and Countering Emotional Behaviors), we conducted two studies guided by the ORBIT model. Study 1 was a single-case design experiment (N = 18); Study 2 was a pilot feasibility study (N = 30). In both studies, participants were randomized to receive one of the three treatment modules. Study 1 examined implementation targets, changes in smoking for coping motives, and changes in smoking rate. Study 2 examined overall feasibility and participant-rated acceptability, and changes in smoking rate. Results Study 1: Treatment implementation targets were met by 3/5 Mindfulness participants, 2/4 Practice Quitting participants, and 0/6 Countering Emotional Behaviors participants. The Practice Quitting condition led to 100% of participants meeting the clinically significant threshold in smoking for coping motives. Incidence of quit attempts ranged from 0-50%, and smoking rate was reduced by 50% overall. Study 2: Recruitment and retention met feasibility targets, with 97% of participants completing all four treatment sessions. Participants reported high treatment satisfaction by qualitative responses and rating scales (M = 4.8/ 5.0). Incidence of quit attempts ranged from 25-58%, and smoking rate was reduced by 56% overall. Conclusions These two small-N studies provide complementary findings on internal validity and implementation of the novel intervention. While Study 1 provided initial support for plausibility of clinically significant change, Study 2 provided data on key feasibility parameters. Implications Smoking cessation for individuals with COPD is medically critical. We conducted an early-phase evaluation of a novel behavioral treatment focused on reducing smoking for coping motives. Results provided initial support for plausibility of clinically significant change and feasibility of the intervention.

IntroductionThe apolipoprotein E (APOE) gene is the strongest known genetic risk factor for sporadic Alzheimer disease (AD). APOE can be used as an enrichment strategy or inclusion criterion for AD prevention trials. Personal genomics companies market direct-to-consumer (DTC) genetic tests, including APOE. We assessed DTC APOE testing usage among enrollees of the University of California Irvine Consent-to-Contact Registry, an online recruitment registry, and attitudes toward using this information in clinical trial recruitment.MethodsWe emailed links to an electronic survey to registry enrollees age 50 years or older. We assessed participants' use of DTC services, willingness to learn APOE status, and willingness to share genetic information. Logistic regression models assessed relationships between DTC testing usage and demographic characteristics, and with willingness to share results to assist trial recruitment.ResultsAmong 1312 responders (57% response rate), few (7%) had used DTC testing for APOE. Non-Hispanic Asian enrollees were 93% less likely to have used DTC testing, compared with non-Hispanic Whites [95% confidence interval: (0.01, 0.67)]. Willingness to share APOE information for study recruitment was >90% for both users and nonusers.ConclusionsMatching participants to trials on the basis of DTC APOE information may be an effective way to streamline AD prevention trial recruitment.

Recruitment registries are novel tools to accelerate Alzheimer disease research accrual. Optimal methods to populate such registries remain largely unstudied. We sent postcards with 3 unique taglines (Alzheimer's Prevention Research, brain health research, general research) to 100,000 local residents aged 50 years and older to assess the effectiveness of recruiting to an online recruitment registry by mail. The postcard campaign recruited 273 new registry enrollees (0.27% overall response rate). Neither the response rate nor the demographic characteristics of recruited participants differed by the postcard tagline. These results suggest that direct mail may not be the most cost-effective approach to recruit participants to online registries.

BackgroundPreclinical Alzheimer's disease clinical trials test candidate treatments in individuals with biomarker evidence but no cognitive impairment. Participants are required to co-enroll with a knowledgeable study partner, to whom biomarker information is disclosed.ObjectiveWe investigated whether reluctance to share biomarker results is associated with viewing the study partner requirement as a barrier to preclinical trial enrollment.DesignWe developed a nine-item assessment on views toward the study partner requirement and performed in-person interviews based on a hypothetical clinical trial requiring biomarker testing and disclosure.SettingWe conducted interviews on campus at the University of California, Irvine.ParticipantsTwo hundred cognitively unimpaired older adults recruited from the University of California, Irvine Consent-to-Contact Registry participated in the study.MeasurementsWe used logistic regression models, adjusting for potential confounders, to examine potential associations with viewing the study partner requirement as a barrier to preclinical trial enrollment.ResultsEighteen percent of participants reported strong agreement that the study partner requirement was a barrier to enrollment. Ten participants (5%) agreed at any level that they would be reluctant to share their biomarker result with a study partner. The estimated odds of viewing the study partner requirement as a barrier to enrollment were 26 times higher for these participants (OR=26.3, 95% CI 4.0, 172.3), compared to those who strongly disagreed that they would be reluctant to share their biomarker result. Overall, participants more frequently agreed with positive statements than negative statements about the study partner requirement, including 76% indicating they would want their study partner with them when they learned biomarker results.ConclusionsThis is one of the first studies to explore how potential preclinical Alzheimer's disease trial participants feel about sharing their personal biomarker information with a study partner. Most participants viewed the study partner as an asset to trial enrollment, including having a partner present during biomarker disclosure.

Reluctance to undergo lumbar puncture (LP) is a barrier to neurological disease biomarker research. We assessed whether an educational intervention increased willingness to consider research LP and whether message framing modified intervention effectiveness. We randomly assigned 851 recruitment registry enrollees who had previously indicated they were unwilling to be contacted about studies requiring LP to gain or loss framed video educational interventions describing the procedure and the probability of experiencing adverse events. The gain framed intervention emphasized the proportion of individuals free of adverse events; the loss frame emphasized the proportion experiencing adverse events. The primary outcome for the study was the participant's post-intervention agreement to be contacted about studies requiring LP. Participants were mean (SD) age 60.1 years (15.7), 69% female (n = 591), and mostly college educated and white. Among the 699 participants who completed the study, 43% (95% CI: 0.39, 0.47; n = 301) changed their response to agree to be contacted about studies requiring LP. We estimated that participants randomized to the gain framed intervention had 67% higher odds of changing their response compared to those randomized to the loss frame (Odds Ratio = 1.67; 95% CI: 1.24, 2.26; p < 0.001). A classification and regression tree model identified participants' pre-intervention willingness as the strongest predictor of changing response. Education, in particular education that alerts participants to the probability of not experiencing adverse events, may be an effective tool to increase participation rates in research requiring LP.

Smoking-induced relief of craving and withdrawal promotes continued cigarette use. Understanding how relief is produced and the role of nicotine in this process may facilitate development of new smoking-cessation therapies. As the US Food and Drug Administration considers setting a standard for reduced nicotine content in cigarettes to improve public health, knowledge of how nicotine contributes to relief also can inform policy. We assessed effects of nicotine using resting state functional magnetic resonance imaging (MRI) and behavioral assessments of craving and negative affect. Twenty-one young (18-25 years old) daily smokers underwent overnight abstinence on 4 days. On each of the following mornings, they self-rated their cigarette craving and negative affect and underwent resting-state functional MRI (fMRI) before and after smoking a cigarette that delivered 0.027, 0.110, 0.231, or 0.763 mg of nicotine. Functional connectivity between the anterior insula and anterior cingulate cortex (ACC) and between the nucleus accumbens and orbitofrontal cortex (OFC) was assessed. Smoking reduced craving, negative affect, and nucleus accumbens-OFC connectivity irrespective of nicotine dose, with positive correlations of the effects on behavioral and connectivity measures. Only the highest nicotine dose (0.763 mg) reduced right anterior insula-ACC connectivity; this reduction was positively correlated with the behavioral effects of the 0.763-mg dose only. While nicotine-based therapies may act on right anterior insula-ACC functional circuits to facilitate smoking cessation, non-nicotine (eg, the conditioned and sensorimotor) aspects of smoking may promote cessation by reducing OFC-accumbens connectivity to alleviate withdrawal.

ObjectiveAll Alzheimer disease (AD) clinical trials, including those enrolling patients with mild cognitive impairment (MCI), require dyadic participation. The purpose of this study was to elucidate how people with MCI and their study partners decide whether to enroll in clinical trials.MethodsThis was a mixed methods interview study. We interviewed patient participants with a consensus research diagnosis of MCI and their study partners. Interviews examined how dyads decide whether to enroll in a clinical trial and whether AD biomarker testing affects willingness to enroll.ResultsThough most MCI patients and study partners would decide in partnership whether to enroll in a clinical trial, agreement was lower among nonspousal, compared with spousal, dyads. Deterrents to enrollment included concerns about patient safety and inconvenience, especially for study partners. Motivators to enrollment included altruism, the desire to contribute to research, hope for patient benefit, and the desire to learn more about the patient's condition. When asked open-ended questions about motivators to enroll in trials, few patients cited access to biomarker testing specifically, though most expressed a desire to undergo biomarker testing when asked directly.ConclusionSpousal and nonspousal MCI dyads may approach clinical trial decisions differently. Future research should investigate how AD biomarker testing affects participants' willingness to enroll in trials.

BackgroundThe experiences of biomarker-ineligible cognitively normal persons can inform trial conduct and the translation of preclinical Alzheimer's disease (AD) into clinical practice.MethodsWe interviewed 33 persons whose "not elevated" brain amyloid imaging biomarker result made them ineligible for a preclinical AD trial.ResultsMost participants (n = 17) reported being informed that they did not demonstrate adequately elevated amyloid to qualify, whereas some (n = 14) reported being told they had no amyloid or plaques. Relief (n = 17) and disappointment related to not being able to participate (n = 12) were the most common reactions to results. Nearly all participants would have made healthy lifestyle changes if they had received an "elevated" result, would have another scan, and would participate in another AD prevention trial.ConclusionsAlthough some participants may misconstrue results, disclosure of a "not elevated" amyloid result in the research setting causes little behavior change; willingness to participate in AD research remains.

To achieve the national agenda of developing improved therapies for Alzheimer's disease (AD), greater community engagement and public trust are needed. Ensuring satisfaction among those enrolling in studies is one means to facilitate these goals. We performed telephone interviews to assess satisfaction with the disclosure of study results among thirteen individuals who were enrolled as participants or study partners in a Phase 3 clinical trial for mild AD. Most participants were at least somewhat satisfied with the manner of disclosure. Two participants were dissatisfied; these participants learned results through the media. Most participants indicated that their preference would have been to learn results through the site study team. Ten participants indicated that they wished to learn randomization assignment and several indicated a desire to learn more details about study data. Future trials should undertake a systematic approach to disclosing study results and assessing participant satisfaction with the process.

Cigarette craving contributes substantially to the maintenance of tobacco use disorder. Behavioral strategies to regulate craving may facilitate smoking cessation but remain underexplored. We adapted an emotion-regulation strategy, using proximal/distal self-positioning, to the context of cigarette craving to examine craving regulation in 42, daily smokers (18-25 years old). After overnight abstinence from smoking, before and after smoking their first cigarette of the day, participants viewed videos of natural scenes presenting young adults who were either smoking cigarettes ("smoke") or not ("non-smoke"). Before each video, participants were instructed to imagine themselves either immersed in the scene ("close") or distanced from it ("far"). They rated their craving after each video. Task-based fMRI data are presented for a subsample of participants (N = 21). We found main effects of smoking, instruction, and video type on craving-lower ratings after smoking than before, following the "far" vs. "close" instructions, and when viewing non-smoke vs. smoke videos. Before smoking, "smoke" vs. "non-smoke" videos elicited activation in, orbitofrontal cortex, anterior cingulate, lateral parietal cortex, mid-occipital cortex, ventral striatum, dorsal caudate, and midbrain. Smoking reduced activation in anterior cingulate, left inferior frontal gyrus, and bilateral temporal poles. Activation was reduced in the ventral striatum and medial prefrontal cortex after the "far" vs. the "close" instruction, suggesting less engagement with the stimuli during distancing. The results indicate that proximal/distal regulation strategies impact cue-elicited craving, potentially via downregulation of the ventral striatum and medial prefrontal cortex, and that smoking during abstinence may increase cognitive control capacity during craving regulation.

RationalePolicies that establish a standard for reduced nicotine content in cigarettes can decrease the prevalence of smoking in the USA. Cigarettes with nicotine yields as low as 0.05 mg produce substantial occupancy of nicotinic acetylcholine receptors (26%), but women and men respond differently to these cigarettes.ObjectiveThis study aimed to measure responses to smoking cigarettes that varied widely in nicotine yields, investigating whether sex differences in the effects on craving, withdrawal, and affect would be observed at even lower nicotine yields than previously studied, and in young smokers.MethodsOvernight abstinent young smokers (23 men, 23 women, mean age 22.18) provided self-reports of craving, withdrawal, and affect before and after smoking cigarettes with yields of 0.027, 0.110, 0.231, or 0.763 mg nicotine, and evaluated characteristics of each cigarette.ResultsCompared to abstinent young men, abstinent young women reported greater negative affect, psychological withdrawal, and sedation, all of which were relieved equally by all cigarettes. Men but not women reported greater craving reduction, perceived nicotine content, and cigarette liking with increasing nicotine dose.ConclusionsMen may experience less smoking-related relief of craving, and enjoy cigarettes less, if nicotine yields are reduced to very low levels. Conversely, women respond equally well to cigarettes with nicotine yields as low as 0.027 mg as to cigarettes with nicotine yields 28-fold higher (0.763 mg). These differences are relevant for policy regarding reduced nicotine in cigarettes and may influence the efficacy and acceptability of reduced-nicotine cigarettes as smoking cessation aids.

BackgroundMild cognitive impairment (MCI) has an uncertain etiology and prognosis and may be challenging for clinicians to discuss with patients and families. Amyloid imaging may aid specialists in determining MCI etiology and prognosis, but creates novel challenges related to disease labeling.MethodsWe convened a workgroup to formulate recommendations for clinicians providing care to MCI patients.ResultsClinicians should use the MCI diagnosis to validate patient and family concerns and educate them that the patient's cognitive impairment is not normal for his or her age and education level. The MCI diagnosis should not be used to avoid delivering a diagnosis of dementia. For patients who meet Appropriate Use Criteria after standard-of-care clinical workup, amyloid imaging may position specialists to offer more information about etiology and prognosis. Clinicians must set appropriate expectations, including ensuring that patients and families understand the limitations of amyloid imaging. Communication of negative results should include that patients remain at elevated risk for dementia and that negative scans do not indicate a specific diagnosis or signify brain health. Positive amyloid imaging results should elicit further monitoring and conversations about appropriate advance planning. Clinicians should offer written summaries, including referral to appropriate social services.ConclusionsIn patients with MCI, there is a need to devote considerable time and attention to patient education and shared decision-making. Amyloid imaging may be a tool to aid clinicians. Careful management of patient expectations and communication of scan results will be critical to the appropriate use of amyloid imaging information.

IntroductionAmyloid imaging is a tool that has recently become available to dementia specialists evaluating patients with possible Alzheimer's disease. Studies have assessed the impact of amyloid imaging on diagnostic and treatment decisions, but patient and family perspectives have received less attention.MethodsTo examine how amyloid imaging affects the diagnostic experience of patients and families, we interviewed members of 26 patient-caregiver dyads with whom a neurologist discussed the option of amyloid positron emission tomography.ResultsMost participants who chose to undergo amyloid imaging would choose to do so again. Regardless of the scan outcome, patients and caregivers commonly expressed relief on learning the scan results. Some participants expressed expectations that were beyond scan capabilities.DiscussionAmyloid imaging may provide information that patients and their families find useful. Clinicians must set correct expectations and ensure that families understand the limitations of amyloid imaging.

The use of cigarettes delivering different nicotine doses allows evaluation of the contribution of nicotine to the smoking experience. We compared responses of 46 young adult smokers to research cigarettes, delivering 0.027, 0.110, 0.231, or 0.763 mg nicotine, and conventional cigarettes. On five separate days, craving, withdrawal, affect, and sustained attention were measured after overnight abstinence and again after smoking. Participants also rated each cigarette, and the nicotine metabolite ratio (NMR) was used to identify participants as normal or slow metabolizers. All cigarettes equally alleviated craving, withdrawal, and negative affect in the whole sample, but normal metabolizers reported greater reductions of craving and withdrawal than slow metabolizers, with dose-dependent effects. Only conventional cigarettes and, to a lesser degree, 0.763-mg nicotine research cigarettes increased sustained attention. Finally, there were no differences between ratings of lower-dose cigarettes, but the 0.763-mg cigarettes and (even more so) conventional cigarettes were rated more favorably than lower-dose cigarettes. The findings indicate that smoking-induced relief of craving and withdrawal reflects primarily non-nicotine effects in slow metabolizers, but depends on nicotine dose in normal metabolizers. By contrast, relief of withdrawal-related attentional deficits and cigarette ratings depend on nicotine dose regardless of metabolizer status. These findings have bearing on the use of reduced-nicotine cigarettes to facilitate smoking cessation and on policy regarding regulation of nicotine content in cigarettes. They suggest that normal and slow nicotine metabolizers would respond differently to nicotine reduction in cigarettes, but that irrespective of metabolizer status, reductions to

Senescence and apoptosis are two fundamental cellular processes that play crucial roles in various physiological and pathological conditions. Senescence refers to the irreversible growth arrest that cells undergo in response to various stimuli, including telomeric alterations, stress, and oncogenic signaling. Pharmacological and/or genetic removal of senescent cells, also referred to as senolysis, triggers organ rejuvenation and tissue regeneration. Indole-3-carbinol (I3C) is a natural compound contained in Brassicaceae plants and identified in multiple in vitro and in vivo studies as a well-tolerated and effective compound in cancer prevention and therapy. Its anti-cancer properties have been attributed at least in part to its inhibitory activity of proto-oncogenic HECT E3-ubiquitin ligases such as NEDD4 and WWP1. While the tumor suppressive effects of I3C in cancer cell lines have been reported in multiple studies, little is known regarding the biological effects of I3C in primary normal cells, which attain spontaneous cellular senesce over serial passaging. To this end, we used two model systems: mouse embryonic fibroblasts (MEFs) and human primary dermal fibroblasts. Here, we surprisingly show that I3C does increase cellular senescence at early passages, while dramatically reducing the number of senescent cells through the induction of apoptosis in both mouse and human primary cells. Thus, our findings support the notion that I3C acts as a senolytic compound with important therapeutic implications for the prevention and treatment of aging manifestations. The notion can be readily tested in future clinical trials in humans also in view of the high tolerability and safety previously displayed by I3C in preclinical and clinical studies. [ABSTRACT FROM AUTHOR]

Objectives: To examine the influence of sociodemographic factors on employment changes among adult children following onset of parental Alzheimer's disease and related dementia (ADRD). Methods: We used Health and Retirement Study (2010–2018; N = 20,110) data to examine adult child (ages 50–70) changes in employment and work hours at onset of parental ADRD and potential variation by gender, age, race, ethnicity, and education. Results: Parental ADRD onset was not associated with changes in adult child employment overall, although associations differed substantially across subpopulations defined by education level. Sons with the lowest education were least likely to cease employment, while daughters with the lowest education were most likely to reduce work hours. Sons at older ages were increasingly likely to reduce work hours or end employment following parental ADRD onset. Discussion: The potential impact of parental ADRD on adult child employment is complex and should be considered in the context of sociodemographic factors. [ABSTRACT FROM AUTHOR]

Delay of gratification and inhibitory control are generally considered measures of self-control. In humans, individual differences in measures of self-control are associated with a host of behavioral, neurological, cognitive, and health-related outcomes. Self-control is not unique to humans and has been demonstrated in a variety of nonhuman species using a variety of paradigms. In this study, the effect of sex and age on delay of gratification performance, as measured by the hybrid delay task, was tested in a sample of 88 chimpanzees. Additionally, whether individual differences in hybrid delay task performance were associated with different aspects of personality was examined in this study. Contrary to reports in human subjects, geriatric male chimpanzees were found to perform more efficiently than adult males, while no age differences were found between geriatric and adult females. Indeed, delay of gratification efficiency was positively associated with age in males and negatively associated with age in females. Chimpanzees that performed more efficiently on the hybrid delay task were also found to be rated as more intelligent, more extraverted, and less impulsive. These findings suggest that objective measures of efficiency in delay of gratification tasks are associated with different dimensions of personality, which have some overlapping construct validity. [ABSTRACT FROM AUTHOR]

Evidence from 220 small business start-ups in both managed and unmanaged shopping centres in New Zealand shows that the difference in failure rates between the two are statistically significant under one definitions of failure, as defined by Watson and Everett (1996). Average annual failure rates range from 0.5% to 9.6% in this study compared with much larger government reported 'discontinuance' rates, thus supporting the notion that the actual small business failure experience requires closer and more detailed examination before the 'risk of failure 'for small businesses can be understood and not assumed to be the same as the lack of continuance. This study suggests that small business failure rates would be best modelled and reported in order to provide a more accurate assessment of failure rates as well as a deeper understanding that 'discontinuance' is not necessarily failure' and not, therefore, to be confused with a risk measure., Introduction According to the New Zealand Ministry of Economic Development (2001), New Zealand is 'predominately a country of small business'. They represent about half of the full-time employees in New [...]