Race-Ethnicity, Rurality, and Age in Prospective Preferences and Concerns Regarding Closed-Loop Implanted Neural Devices.

OBJECTIVE: Responsive and human-centered neurotechnology development requires attention to public perceptions, particularly among groups underserved by existing treatments. METHODS: The authors conducted a preregistered nationally representative survey (https://osf.io/ej9h2) using the NORC at the University of Chicago AmeriSpeak panel. One vignette compared an implanted neural device with surgical resection in a scenario involving epilepsy, and another compared an implanted neural device with medications in a scenario involving mood disorders. The survey also contained questions about respondents' confidence that a device would be available if needed and confidence that enough research has been conducted among people like themselves. Responses were entered into nested survey-weighted logistic regression models, including a base demographic model (to test the overall effect of demographic factors) and an adjusted model that also included socioeconomic, religious and political, and health care access predictors. RESULTS: A total of 1,047 adults responded to the survey, which oversampled Black non-Hispanic (N=214), Hispanic (N=210), and rural (N=219) Americans. In the base demographic model, older Americans were more likely to prefer an implanted device in the two scenarios, and non-Hispanic Black Americans were less likely than non-Hispanic White Americans to prefer a device; rural Americans were less confident than urban or suburban Americans in having access, and non-Hispanic Black and rural Americans were less confident that enough research has been conducted among people like themselves. In adjusted models, income was a key mediator, partially explaining the effect of age and the contrast between Black and White non-Hispanic respondents on preferences for a device in the epilepsy scenario and fully explaining the effect of rurality on confidence in access. CONCLUSIONS: Demographic differences in prospective preferences and concerns highlight the importance of including members of underserved communities in neurotechnology development.

Socioemotional dysfunction and the greater good: a case study.

Moral cognition has largely been studied via dilemmas in which making a utilitarian choice causes instrumental harm (negative dimension). Studies of utilitarianism link this behavior with socioemotional unresponsiveness. However, there is a positive dimension of utilitarianism in which one sacrifices the good of oneself or close others for the overall welfare. We measured utilitarian choices multidimensionally in a patient with behavioral variant frontotemporal dementia (bvFTD), incorporating dilemmas accounting for negative and positive dimensions. Despite socioemotional deficits our patient was highly utilitarian in the positive, dimension of utilitarianism. This case study challenges the tendency to automatically associate bvFTD with antisocial tendencies.

Patient experiences of resection versus responsive neurostimulation for drug-resistant epilepsy.

This study explored illness experiences and decision-making among patients with epilepsy who underwent two different types of surgical interventions: resection versus implantation of the NeuroPace Responsive Neurostimulation System (RNS). We recruited 31 participants from a level four epilepsy center in an academic medical institution. We observed 22 patient clinic visits (resection: n = 10, RNS: n = 12) and conducted 18 in-depth patient interviews (resection: n = seven, RNS: n = 11); most visits and interviews included patient caregivers. Using an applied ethnographic approach, we identified three major themes in the experiences of resection versus RNS patients. First, for patients in both cohorts, the therapeutic journey was circuitous in ways that defied standardized first-, second-, and third- line of care models. Second, in conceptualizing risk, resection patients emphasized the permanent loss of "taking out" brain tissue whereas RNS patients highlighted the reversibility of "putting in" a device. Lastly, in considering benefit, resection patients perceived their surgery as potentially curative while RNS patients understood implantation as primarily palliative with possible additional diagnostic benefit from chronic electrocorticography. Insight into the perspectives of patients and caregivers may help identify key topics for counseling and exploration by clinicians.

Effect of collaborative dementia care on potentially inappropriate medication use: Outcomes from the Care Ecosystem randomized clinical trial.

INTRODUCTION: Potentially inappropriate medications (PIMs) cause adverse events and death. We evaluate the Care Ecosystem (CE) collaborative dementia care program on medication use among community-dwelling persons living with dementia (PLWD). METHODS: Secondary analysis of a randomized clinical trial (RCT) comparing CE to usual care (UC) on changes in PIMs, over 12 months between March 2015 and May 2020. Secondary outcomes included change in number of medications, clinically relevant PIMs, and anti-dementia medications. RESULTS: Of 804 PLWD, N = 490 had complete medication data. The CE resulted in significantly fewer PIMs compared to UC (-0.35; 95% CI, -0.49 to -0.20; P < 0.0001). Number needed to prevent an increase in 1 PIM was 3. Total medications, PIMs for dementia or cognitive impairment, CNS-active PIMs, anticholinergics, benzodiazepines, and opioids were also fewer. Anti-dementia medication regimens were modified more frequently. CONCLUSION: The CE medication review intervention embedded in collaborative dementia care optimized medication use among PLWD. HIGHLIGHTS: Compared to usual care (UC), the Care Ecosystem (CE) medication review intervention prevented increases in potentially inappropriate medications (PIMs). Use of anticholinergics, benzodiazepines, and opioids were significantly reduced, with a trend for antipsychotics. Anti-dementia medications were adjusted more frequently. The CE medication review intervention embedded in collaborative dementia care optimized medication use.

Clinician preferences for neurotechnologies in pediatric drug-resistant epilepsy: A discrete choice experiment.

OBJECTIVE: Novel and minimally invasive neurotechnologies offer the potential to reduce the burden of epilepsy while avoiding the risks of conventional resective surgery. Few neurotechnologies have been tested in randomized controlled trials with pediatric populations, leaving clinicians to face decisions about whether to recommend these treatments with insufficient evidence about the relevant risks and benefits. This study specifically explores the preferences of clinicians for treating pediatric drug-resistant epilepsy (DRE) with novel neurotechnologies. METHODS: A discrete-choice experiment (DCE) was designed to elicit the preferences of clinicians with experience in treating children with DRE using novel neurotechnological interventions. The preferences for six key attributes used when making treatment decisions (chances of clinically significant improvement in seizures, major and minor risks from intervention, availability of evidence, financial burden for the family, and access to the intervention) were estimated using a conditional logit model. The estimates from this model were then used to predict the adoption of existing novel neurotechnological interventions. RESULTS: Sixty-eight clinicians completed the survey: 33 neurosurgeons, 28 neurologists, and 7 other clinicians. Most clinicians were working in the United States (74%), and the remainder (26%) in Canada. All attributes, apart from the nearest location with access to the intervention, influenced preferences significantly. The chance of clinically significant improvement in seizures was the most positive influence on clinician preferences, but low-quality evidence and a higher risk of major complications could offset these preferences. Of the existing neurotechnological interventions, vagus nerve stimulation was predicted to have the highest likelihood of adoption; deep brain stimulation had the lowest likelihood of adoption. SIGNIFICANCE: The preferences of clinicians are drive primarily by the likelihood of achieving seizure freedom for their patients, but preferences for an intervention are largely eradicated if only low quality of evidence supporting the intervention is available. Until better evidence supporting the use of potentially effective, novel neurotechnologies becomes available, clinicians are likely to prefer more established treatments.

Wisdom and fluid intelligence are dissociable in healthy older adults.

OBJECTIVES: The relationship between wisdom and fluid intelligence (Gf) is poorly understood, particularly in older adults. We empirically tested the magnitude of the correlation between wisdom and Gf to help determine the extent of overlap between these two constructs. DESIGN: Cross-sectional study with preregistered hypotheses and well-powered analytic plan (https://osf.io/h3pjx). SETTING: Memory and Aging Center at the University of California San Francisco, located in the USA. PARTICIPANTS: 141 healthy older adults (mean age = 76 years; 56% female). MEASUREMENTS: Wisdom was quantified using a well-validated self-report-based scale (San Diego Wisdom Scale or SD-WISE). Gf was assessed via composite measures of processing speed (Gf-PS) and executive functioning (Gf-EF). The relationships of SD-WISE scores to Gf-PS and Gf-EF were tested in bivariate correlational analyses and multiple regression models adjusted for demographics (age, sex, and education). Exploratory analyses evaluated the relationships between SD-WISE and age, episodic memory performance, and dorsolateral and ventromedial prefrontal cortical volumes on magnetic resonance imaging. RESULTS: Wisdom showed a small, positive association with Gf-EF (r = 0.181 [95% CI 0.016, 0.336], p = .031), which was reduced to nonsignificance upon controlling for demographics, and no association with Gf-PS (r = 0.019 [95% CI -0.179, 0.216], p = .854). Wisdom demonstrated a small, negative correlation with age (r = -0.197 [95% CI -0.351, -0.033], p = .019), but was not significantly related to episodic memory or prefrontal volumes. CONCLUSIONS: Our findings indicate that most of the variance in wisdom (>95%) is unaccounted for by Gf. The independence of wisdom from cognitive functions that reliably show age-associated declines suggests that it may hold unique potential to bolster decision-making, interpersonal functioning, and other everyday activities in older adults.

Caregiver "objective attitude" toward patients with neurodegenerative disease: Consequences for caregiver strain and relationship closeness.

Many caregivers of patients with neurodegenerative disease experience physical and psychological strain, which is associated with negative health outcomes. Caregiver strain may be partly attributable to negative emotional responses (e.g.of resentment) to the behavioral, cognitive, and physical changes associated with patients' disease. The philosopher Peter Strawson observed that in dealing with people who have neurological impairments, we often choose to suspend such emotional responses, adopting what he labeled the "objective attitude," though this may come at the expense of our relationships with them. In this study, we assessed the mediating effect of caregivers' adoption of the objective attitude on caregiver strain and relationship closeness in the setting of disease progression. Caregivers of patients with neurodegenerative disorders (n = 215) completed the Clinical Dementia Rating, Relationship-Closeness scale, Caregiver Strain Index, and a novel questionnaire assessing the adoption of the objective attitude. A structural equation model assessing associations among these variables demonstrated good fit (χ2 (88)=164.621, p < 0.001; CFI = 0.929, RMSEA = 0.064.) and showed that adoption of the objective attitude mediated the association between disease progression and relationship closeness (total ß= -0.233, 95% CI: -0.351, -0.113; indirect ß= -0.483, 95% CI: -0.602, -0.364; direct ß = 0.250, 95% CI: 0.117, 0.384), but did not mediate the association between disease progression and caregiver strain (total ß = 0.323, 95% CI: 0.234, 0.412; indirect ß = 0.089, 95% CI: -0.027, 0.206; direct ß = 0.153, 95% CI: -0.043, 0.349). For future work, we propose longitudinal measurements of these constructs to test the directionality of associations and consideration of how models for caregiver support can draw upon interdisciplinary insights.

The costs of dementia subtypes to California Medicare fee-for-service, 2015.

INTRODUCTION: Dementia is among the costliest of medical conditions, but it is not known how these costs vary by dementia subtype. METHODS: The effect of dementia diagnosis subtype on direct health care costs and utilization was estimated using 2015 California Medicare fee-for-service data. Potential drivers of increased costs in Lewy body dementia (LBD), in comparison to Alzheimer's disease, were tested. RESULTS: 3,001,987 Medicare beneficiaries were identified, of which 8.2% had a dementia diagnosis. Unspecified dementia was the most common diagnostic category (59.6%), followed by Alzheimer's disease (23.2%). LBD was the costliest subtype to Medicare, on average, followed by vascular dementia. The higher costs in LBD were explained in part by falls, urinary incontinence or infection, depression, anxiety, dehydration, and delirium. DISCUSSION: Dementia subtype is an important predictor of health care costs. Earlier identification and targeted treatment might mitigate the costs associated with co-occurring conditions in LBD.

Informed Consent for the Human Research Subject with a Neurologic Disorder.

The doctrine of informed consent sits at the intersection of law, ethics, and neuroscience, posing unique challenges for human subject research involving neurological patients. These challenges are compounded by the variegated nature of both neurological injury and the law governing research consent. This article provides a framework for investigators likely to encounter subjects with some degree of neurological impairment, whose capacity to consent requires scrupulous assessment prior to enrollment in research trials. We consider several researches and disease contexts-from emergency epilepsy research to long-term dementia research-and clarify the ethical and legal principles governing consent for participation in each. We additionally explore empirical research on consent capacity and survey several areas of emerging ethical import that will require the attention of investigators in decades to come.

Trends in Recruitment Rates for Acute Stroke Trials, 1990-2014.

BACKGROUND AND PURPOSE: Slow recruitment in acute stroke trials hampers the evaluation of new therapies and delays the adoption of effective therapies into clinical practice. This systematic review evaluates whether recruitment efficiency and rates have increased in acute stroke trials from 1990 to 2014. METHODS: Acute stroke trials from 2010 to 2014 were identified by a search of PubMed, Medline, the Cochrane Database of Research in Stroke, and the Stroke Trials Registry. These trials were compared to a previously published data set of trials conducted from 1990 to 2004. RESULTS: The median recruitment efficiency of trials from 1990 to 2004 was 0.41 participants/site/month compared with 0.26 participants/site/month from 2010 to 2014 (P=0.14). The median recruitment rate of trials from 1990 to 2004 was 26.8 participants/month compared with 19.0 participants/month from 2010 to 2014 (P=0.13). CONCLUSIONS: For acute stroke trials, neither recruitment efficiency nor recruitment rates have increased over the past 25 years and, if anything, have declined.

Development of an adaptive, personalized, and scalable dementia care program: Early findings from the Care Ecosystem.

Katherine Possin and colleagues report on the implementation, development, and early findings of the Care Ecosystem, an adaptive, personalized, and scalable dementia care program.

Neuroeconomic dissociation of semantic dementia and behavioural variant frontotemporal dementia.

Many neuropsychiatric disorders are marked by abnormal behaviour and decision-making, but prevailing diagnostic criteria for such behaviours are typically qualitative and often ambiguous. Behavioural variant frontotemporal dementia and semantic variant primary progressive aphasia (also called semantic dementia) are two clinical variants of frontotemporal dementia with overlapping but distinct anatomical substrates known to cause profound changes in decision-making. We investigated whether abnormal decision-making in these syndromes could be more precisely characterized in terms of dissociable abnormalities in patients' subjective evaluations of valence (positive versus negative outcome) and of time (present versus future outcome). We presented 28 patients with behavioural variant frontotemporal dementia, 14 patients with semantic variant primary progressive aphasia, 25 patients with Alzheimer's disease (as disease controls), and 61 healthy older control subjects with experimental tasks assaying loss aversion and delay discounting. In general linear models controlling for age, gender, education and Mini-Mental State Examination score, patients with behavioural variant frontotemporal dementia were less averse to losses than control subjects (P < 0.001), while patients with semantic variant primary progressive aphasia discounted delayed rewards more steeply than controls (P = 0.019). There was no relationship between loss aversion and delay discounting across the sample, nor in any of the subgroups. These findings suggest that abnormal behaviours in neurodegenerative disease may result from the disruption of either of two dissociable neural processes for evaluating the outcomes of action. More broadly, these findings suggest a role for computational methods to supplement traditional qualitative characterizations in the differential diagnosis of neuropsychiatric disorders.

Inability to consent does not diminish the desirability of stroke thrombolysis.

OBJECTIVE: Some have argued that physicians should not presume to make thrombolysis decisions for incapacitated patients with acute ischemic stroke because the risks and benefits of thrombolysis involve deeply personal values. We evaluated the influence of the inability to consent and of personal health-related values on older adults' emergency treatment preferences for both ischemic stroke and cardiac arrest. METHODS: A total of 2,154 US adults age ≥50 years read vignettes in which they had either suffered an acute ischemic stroke and could be treated with thrombolysis, or had suffered a sudden cardiac arrest and could be treated with cardiopulmonary resuscitation. Participants were then asked (1) whether they would want the intervention, or (2) whether they would want to be given the intervention even if their informed consent could not be obtained. We elicited health-related values as predictors of these judgments. RESULTS: Older adults were as likely to want stroke thrombolysis when unable to consent (78.1%) as when asked directly (76.2%), whereas older adults were more likely to want cardiopulmonary resuscitation when unable to consent (83.6% compared to 75.9%). Greater confidence in the medical system and reliance on statistical information in decision making were both associated with desiring thrombolysis. INTERPRETATION: Older adults regard thrombolysis no less favorably when considering a situation in which they are unable to consent. These findings provide empirical support for recent professional society recommendations to treat ischemic stroke with thrombolysis in appropriate emergency circumstances under a presumption of consent.

The salience network causally influences default mode network activity during moral reasoning.

Large-scale brain networks are integral to the coordination of human behaviour, and their anatomy provides insights into the clinical presentation and progression of neurodegenerative illnesses such as Alzheimer's disease, which targets the default mode network, and behavioural variant frontotemporal dementia, which targets a more anterior salience network. Although the default mode network is recruited when healthy subjects deliberate about 'personal' moral dilemmas, patients with Alzheimer's disease give normal responses to these dilemmas whereas patients with behavioural variant frontotemporal dementia give abnormal responses to these dilemmas. We hypothesized that this apparent discrepancy between activation- and patient-based studies of moral reasoning might reflect a modulatory role for the salience network in regulating default mode network activation. Using functional magnetic resonance imaging to characterize network activity of patients with behavioural variant frontotemporal dementia and healthy control subjects, we present four converging lines of evidence supporting a causal influence from the salience network to the default mode network during moral reasoning. First, as previously reported, the default mode network is recruited when healthy subjects deliberate about 'personal' moral dilemmas, but patients with behavioural variant frontotemporal dementia producing atrophy in the salience network give abnormally utilitarian responses to these dilemmas. Second, patients with behavioural variant frontotemporal dementia have reduced recruitment of the default mode network compared with healthy control subjects when deliberating about these dilemmas. Third, a Granger causality analysis of functional neuroimaging data from healthy control subjects demonstrates directed functional connectivity from nodes of the salience network to nodes of the default mode network during moral reasoning. Fourth, this Granger causal influence is diminished in patients with behavioural variant frontotemporal dementia. These findings are consistent with a broader model in which the salience network modulates the activity of other large-scale networks, and suggest a revision to a previously proposed 'dual-process' account of moral reasoning. These findings also characterize network interactions underlying abnormal moral reasoning in frontotemporal dementia, which may serve as a model for the aberrant judgement and interpersonal behaviour observed in this disease and in other disorders of social function. More broadly, these findings link recent work on the dynamic interrelationships between large-scale brain networks to observable impairments in dementia syndromes, which may shed light on how diseases that target one network also alter the function of interrelated networks.

Financial errors in dementia: testing a neuroeconomic conceptual framework.

Financial errors by patients with dementia can have devastating personal and family consequences. We developed and evaluated a neuroeconomic conceptual framework for understanding financial errors across different dementia syndromes, using a systematic, retrospective, blinded chart review of demographically-balanced cohorts of patients with Alzheimer's disease (AD, n=100) and behavioral variant frontotemporal dementia (bvFTD, n=50). Reviewers recorded specific reports of financial errors according to a conceptual framework identifying patient cognitive and affective characteristics, and contextual influences, conferring susceptibility to each error. Specific financial errors were reported for 49% of AD and 70% of bvFTD patients (p = 0.012). AD patients were more likely than bvFTD patients to make amnestic errors (p < 0.001), while bvFTD patients were more likely to spend excessively (p = 0.004) and to exhibit other behaviors consistent with diminished sensitivity to losses and other negative outcomes (p < 0.001). Exploratory factor analysis identified a social/affective vulnerability factor associated with errors in bvFTD, and a cognitive vulnerability factor associated with errors in AD. Our findings highlight the frequency and functional importance of financial errors as symptoms of AD and bvFTD. A conceptual model derived from neuroeconomic literature identifies factors that influence vulnerability to different types of financial error in different dementia syndromes, with implications for early diagnosis and subsequent risk prevention.