The impact of resilience on headache disability as measured by the Migraine Disability Assessment (MIDAS).

OBJECTIVE: Our objectives were to examine cross-sectional correlations of headache disability with measures of resilience, anxiety, and depression, and to determine if resilience modified the association between headache severity/frequency and disability. BACKGROUND: Resilience is associated with quality of life and functioning among patients with chronic conditions. We investigated whether resilience strongly mitigates headache-related disability as measured by the Migraine Disability Assessment (MIDAS). METHODS: We prospectively recruited 160 patients with primary headache disorders seen in a tertiary headache medicine program between February 20, 2018 and August 2, 2019. Each participant completed the MIDAS, Conner Davidson Resilience Scale (CDRS-25), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and WHO-5 Well-Being Index. RESULTS: The CDRS-25 score was negatively correlated with the total MIDAS (r = -0.21, p = 0.009), GAD-7 (r = -0.56, p < 0.001), and PHQ-9 scores (r = -0.34, p < 0.001). Well-being inversely correlated with disability (r = -0.37, p < 0.001). Increases in anxiety and depression increased the odds of disability. A 1 point increase in the CDRS-25 score decreased the odds of being severely disabled by 4% (OR = 0.96, 95% CI: 0.94 to 0.99, p = 0.001). However, the CDRS-25 score did not significantly moderate the association between headache days and disability. CONCLUSION: Traits associated with resilience decreased the odds of severe disability from headaches, whereas anxiety, depression, and headache frequency were strongly associated with higher disability from headache.

Comparing the effects of four common drug classes on the progression of mild cognitive impairment to dementia using electronic health records.

The objective of this study was to investigate the potential association between the use of four frequently prescribed drug classes, namely antihypertensive drugs, statins, selective serotonin reuptake inhibitors, and proton-pump inhibitors, and the likelihood of disease progression from mild cognitive impairment (MCI) to dementia using electronic health records (EHRs). We conducted a retrospective cohort study using observational EHRs from a cohort of approximately 2 million patients seen at a large, multi-specialty urban academic medical center in New York City, USA between 2008 and 2020 to automatically emulate the randomized controlled trials. For each drug class, two exposure groups were identified based on the prescription orders documented in the EHRs following their MCI diagnosis. During follow-up, we measured drug efficacy based on the incidence of dementia and estimated the average treatment effect (ATE) of various drugs. To ensure the robustness of our findings, we confirmed the ATE estimates via bootstrapping and presented associated 95% confidence intervals (CIs). Our analysis identified 14,269 MCI patients, among whom 2501 (17.5%) progressed to dementia. Using average treatment estimation and bootstrapping confirmation, we observed that drugs including rosuvastatin (ATE = - 0.0140 [- 0.0191, - 0.0088], p value < 0.001), citalopram (ATE = - 0.1128 [- 0.125, - 0.1005], p value < 0.001), escitalopram (ATE = - 0.0560 [- 0.0615, - 0.0506], p value < 0.001), and omeprazole (ATE = - 0.0201 [- 0.0299, - 0.0103], p value < 0.001) have a statistically significant association in slowing the progression from MCI to dementia. The findings from this study support the commonly prescribed drugs in altering the progression from MCI to dementia and warrant further investigation.

Associations between pituitary-ovarian hormones and cognition in recently menopausal women independent of type of hormone therapy.

OBJECTIVES: To examine associations of pituitary-ovarian hormone levels with cognition before and after different formulations of hormone therapy (HT) or placebo independent of treatment group. METHODS: Recently menopausal, healthy women were randomized to 0.45 mg/day oral conjugated equine estrogens (o-CEE, n = 109), 50 µg/day transdermal 17ß (tE2, n = 107) or placebo pills and patches (n = 146); women on active treatment received oral 200 mg/day micronized progesterone for 12 days per month. Levels of estrone, 17ß-estradiol, follicle stimulating hormone, luteinizing hormone, androstenedione, and testosterone were determined prior to and after 48 months of study participation. Neuropsychological testing was administered at baseline, and months 18, 36 and 48. Latent growth curve models controlling for education level, age, APOE allele status, waist circumference, and treatment examined the trajectories of each cognitive domain after accounting for the effect of hormone levels at baseline and months 18, 36 and 48. A linear multivariate mixed model examined the effect of changes in hormone levels on changes in trajectories of complex attention tasks with varying degrees of difficulty. RESULTS: All women were adherent to treatment at month 48. Higher baseline estrone levels were associated with poorer global cognition, auditory attention and working memory, visual attention, and executive function, but not working memory. Higher levels of baseline 17ß-E2 were associated with poorer cognitive performance, with marginal significance at baseline in speeded language and mental flexibility (p = 0.013). Other hormone levels were not associated with cognition. Controlling for all treatments, hormone levels at baseline and at month 48 did not have any significant correlation with cognitive trajectories over time. SUMMARY: In healthy, recently menopausal women, baseline estrone levels were inversely associated with selected cognitive factors independent of two types of HT or placebo during 4 years of follow-up. Baseline levels of the other pituitary-ovarian hormones studied were not associated with baseline cognition, nor were changes in any hormones associated with changes in cognition during the study. The marginal association between estradiol levels and cognitive factors warrants further investigation. GOV NUMBERS: NCT00154180, NCT00623311.

Evaluation of a Novel Wellness Curriculum on Medical Student Wellbeing and Engagement Demonstrates a Need for Student-Driven Wellness Programming.

PROBLEM: Medical training is stressful and has well-established implications for student wellbeing. Despite widespread efforts to reduce student burnout through wellness programming in medical schools, there is a paucity of literature examining students' perception of wellness and engagement with these programs. As such, we sought to evaluate: 1) medical students' level of engagement with a multifaceted wellness curriculum, 2) factors students perceived as important to wellbeing, and 3) associations with longitudinal measures of wellbeing and perceived stress. Intervention: A multipronged wellness curriculum was instituted at Mayo Clinic Alix School of Medicine-AZ (MCASOM-AZ) in 2017. This includes mental health services, curriculum-embedded seminars, wellness committee (composed of students, faculty, and administration) driven programming, and student proposed wellness activities that are reviewed and funded by the committee. The authors invited students at our institution to complete questionnaires at three timepoints during the 2018-2019 academic year. Questionnaires asked participants to rank eight factors from least to most important to their overall wellbeing. Participants self-reported their participation in each prong of the wellness curriculum and ranked the impact of each on their overall wellbeing. Their wellbeing and perceived stress were measured at each timepoint using validated psychological instruments. Context: As MCASOM-AZ opened in 2017, the student body at the time of study consisted of first- and second-year medical students. All students had the opportunity to engage with all aspects of the wellness curriculum and participate in this study, however participation was elective and all responses were anonymous. Of the MCASOM-AZ student body comprised of 100 students, 58 consented to participate in the study, 41.4% of which were Year 1 and 58.6% of which were Year 2 students. Participant age and gender were collected and were representative of the larger student body. Impact: Students engaged most with student-initiated wellness. They perceived unscheduled time as most impactful to their overall wellbeing with student-initiated activities as second-most impactful. Students with higher perceived stress were more likely than others to use mental health resources, which otherwise ranked lower in importance. Ranking academic performance as important to wellbeing was associated with higher wellbeing. There was no difference in wellbeing between students who participated in the wellness curriculum and those who did not. However, overall student wellbeing increased over the course of the year while perceived stress decreased. Lessons Learned: Medical school programs may benefit from allowing students to direct or contribute to the design of their own wellness curriculum. Additionally, medical education should work toward creating a more supportive learning environment with improved flexibility in order to better meet students' individual needs without compromising their education. Despite having low utilization rates overall, mental health resources remain an important aspect of student support services as they are used by students under greater amounts of perceived stress than their peers.Supplemental data for this article is available online at https://doi.org/10.1080/10401334.2021.2004415 .

Medical students describe their wellness and how to preserve it.

BACKGROUND: Despite widespread efforts to create wellness programming in medical schools, there is a paucity of literature examining students' perception of wellness and perceptions of these programs. With the inaugural class at the Arizona campus of Mayo Clinic Alix School of Medicine (MCASOM-AZ), an opportunity arose to establish an empirically evaluated wellness curriculum that most inclusively and effectively enables medical students to flourish for years to come. The initial wellness offerings included mental health, academic success, and disability services, curriculum-embedded seminars, wellness committee driven programming, and student-proposed wellness activities. We aimed to improve the relevance and impact of medical school wellness curricula by soliciting in-depth and longitudinal perspectives of medical students themselves. As MCASOM-AZ opened in 2017, the student body at the time of study consisted of first- and second-year medical students. METHODS: Employing a mixed methods analysis of qualitative and longitudinal quantitative data, first- and second-year students at a MCASOM-AZ were invited to respond to an anonymous, online year-long survey (baseline, six months and 12 months) during the 2018-2019 academic year and participate in a structured, in-depth and in-person, peer-to-peer interview about their conceptions of wellness and the MCASOM-AZ wellness curriculum and resources. Qualitative data was coded for themes using thematic analysis strategies by independent raters. RESULTS: Nearly half of eligible students completed the baseline survey,1/3 completed all 3 time-points, and 1/5 participated in an in-depth interview. Participant age, gender, and year of school were representative of the larger student body. Although individual conceptions varied, Wellness was consistently highly valued. Family, Academic Performance, and Friends emerged as most important to well-being across time-points. Academic work arose as the largest barrier to wellness. Analysis of qualitative data revealed five themes. Despite individual differences in approaches to wellness, wellbeing was interrelated to the learning environment; mandatory wellness efforts that didn't address the medical culture met with skepticism. CONCLUSIONS: Interview responses provided understanding and context by which to interpret questionnaire responses. Academics was critical to students' identity and wellness, while also the largest barrier. Suggested curricular improvements include restructuring academic work, seamlessly integrating wellness within coursework, and offering optional individualized approaches.

An Agitated Patient With COVID-19 Infection and Early-onset Alzheimer Disease.

Encephalopathy, delirium, and agitation are documented symptoms of coronavirus disease (COVID-19) infection, but research into the management of agitation in the setting of COVID-19 and pre-existing neuropsychiatric disease is ongoing. We present a 55-year-old male patient with early-onset Alzheimer disease and deteriorating mental and functional status who presented to our institution with agitation and persistent COVID-19 positivity on polymerase chain reaction testing. His agitation was improved through pharmacologic optimization including the avoidance of benzodiazepines and initiation of clonidine and prazosin, which temporally coincided with the resolution of his nearly 2-month long COVID-19 positivity.

Integrating a Grassroots Well-Being Curriculum into a Radiation Oncology Residency Program.

PURPOSE: The burnout rate among US radiation oncology residents was 33% in 2016. To our knowledge there are no published interventions addressing burnout among radiation oncology residents. We describe the implementation of a well-being curriculum, cocreated by a psychologist, a medical humanities professional, and radiation oncology attending and resident physicians. METHODS AND MATERIALS: Radiation oncology residents at our institution were surveyed to determine themes that induced burnout. A curriculum was developed, with monthly small group sessions focused on 1 identified topic. Sessions alternated between psychological tool-focused approaches and humanities exercises. These were led by a psychologist or medical humanities professional. Residents were given protected time to attend sessions during business hours. Participation was optional. Participants were assigned a random identifier, and the Stanford Professional Fulfillment Index (PFI) was assessed at baseline and 3-month intervals. PFI trends were analyzed after 1 year. At the end of the year, a focus group was held to evaluate work satisfaction and self-reported interactions with patients and coworkers. This information was used to improve the curriculum. RESULTS: All 12 residents in the radiation oncology program participated in the curriculum. There was an equal number of residents of postgraduate years 2 through 5. Six of the participants were female. Of the participants, 11 completed the PFI. At baseline, 80% of residents met criteria for burnout. This decreased to 67%, 50%, and 33% at 3, 6, and 9 months, respectively. The proportion of residents meeting criteria for very good professional fulfillment was 30%, 56%, 38%, and 22% at baseline and 3, 6, and 9 months, respectively. On average, 9 of 12 residents attended each session. CONCLUSIONS: Our experience demonstrates the feasibility of collaborating with residents in the development of a well-being curriculum to cater programming to their needs, which we believe led to excellent engagement and attendance at each session.

Parental leave policy information during residency interviews.

BACKGROUND: During interviews, medical students may feel uncomfortable asking questions that might be important to them, such as parental leave. Parental leave policies may be difficult for applicants to access without asking the program director or other interviewers. The goal of this study is to evaluate whether parental leave information is presented to prospective residents and whether medical students want this information. METHODS: Fifty-two program directors (PD's) at 3 sites of a single institution received a survey in 2019 to identify whether parental leave information is presented at residency interviews. Medical students received a separate survey in 2020 to identify their preferences. Fisher exact tests, Pearson χ2 tests and Cochran-Armitage tests were used where appropriate to assess for differences in responses. RESULTS: Of the 52 PD's, 27 responded (52%) and 19 (70%) indicated that information on parental leave was not provided to candidates. The most common reason cited was the belief that the information was not relevant (n = 7; 37%). Of the 373 medical students, 179 responded (48%). Most respondents (92%) wanted parental leave information formally presented, and many anticipated they would feel extremely or somewhat uncomfortable (68%) asking about parental leave. The majority (61%) felt that these policies would impact ranking of programs "somewhat" or "very much." CONCLUSIONS: Parental leave policies may not be readily available to interviewees despite strong interest and their impact on ranking of programs by prospective residents.

Compensatory and Lifestyle-Based Brain Health Program for Subjective Cognitive Decline: Self-Implementation versus Coaching.

Although recent studies have explored the potential of multidomain brain health programs, there is a dearth of literature on operationalizing this research to create a clinical treatment program specifically for subjective cognitive decline (SCD). Patients seen by geriatricians in primary care and by behavioral neurology services at our institution presenting with SCD were recruited via a patient-appropriate flyer. After all participants had a 1-h brain health consultation with a neuropsychologist and were provided with program materials, they were randomized to attend a 10-week intervention designed to support program implementation (N = 10) or the control group of implementing the program on their own (N = 11). The program included (1) a calendar-based executive and memory support system for compensatory training and (2) training in healthy lifestyle. There were no significant differences between groups for any outcomes. Participants across both groups showed significant improvements with moderate effect sizes in compensatory strategy use, anxiety symptoms, and daily functioning, which were sustained through 6-month follow-up. They also increased physical activity by the end of the intervention period but did not sustain this through 6-month follow-up. Our pilot study demonstrates preliminary feasibility of a cognitive compensatory and lifestyle-based brain health program. Additional research is recommended to further develop two potentially scalable implementation strategies-coaching and self-implementation after brief consultation.

Current Parental Leave Policies for Medical Students at U.S. Medical Schools: A Comparative Study.

PURPOSE: Parental leave for new parents is essential as they adjust to the physical and psychological changes that accompany childbirth and caring for a newborn. This study sought to determine the current state of parental leave policies for medical students at medical schools in the United States. METHOD: From November to December 2019, 2 researchers independently reviewed the websites of 199 U.S. MD-granting and DO-granting medical schools (including in U.S. territories). Online student handbooks and school webpages were searched for the following keywords: "pregnant" OR "pregnancy" OR "maternity" OR "parent" OR "family" OR "child" OR "birth." Data were analyzed using descriptive statistics. Fisher's exact tests evaluated differences in proportion by group. RESULTS: Of 199 schools, 65 (32.66%) had parental leave policies available online or in the handbook: 39 of 155 (25.16%) MD-granting and 26 of 44 (59.09%) DO-granting schools. Of those policies, 59 (90.77%) were included in the student handbook. Most policies (28, 43.08%) were included as an option within the school's general leave of absence policy. Both parents were included in 38 (58.46%) policies; 23 (35.38%) policies mentioned only mothers; and 4 (6.15%) were unknown. An option to maintain original graduation date was offered in 21 (32.1%) schools' policies. Three schools (4.62%) included adoption as qualifying for parental leave. When comparing MD and DO programs, DO programs were statistically more likely to have a parental leave policy: 39 (25.16%) vs 26 (59.09%); P < .001. CONCLUSIONS: Balancing medical school with pregnancy and childbirth necessitates administrative support to address the inherent scheduling challenges. Currently, many schools lack parental leave policies for medical students that are easily accessible, are separate from formal leaves of absence, allow for at least 12 weeks, and are tailored to the student academic year to ensure on-time completion of medical education.

Predicting future cognitive decline with hyperbolic stochastic coding.

Hyperbolic geometry has been successfully applied in modeling brain cortical and subcortical surfaces with general topological structures. However, such approaches, similar to other surface-based brain morphology analysis methods, usually generate high dimensional features. It limits their statistical power in cognitive decline prediction research, especially in datasets with limited subject numbers. To address the above limitation, we propose a novel framework termed as hyperbolic stochastic coding (HSC). We first compute diffeomorphic maps between general topological surfaces by mapping them to a canonical hyperbolic parameter space with consistent boundary conditions and extracts critical shape features. Secondly, in the hyperbolic parameter space, we introduce a farthest point sampling with breadth-first search method to obtain ring-shaped patches. Thirdly, stochastic coordinate coding and max-pooling algorithms are adopted for feature dimension reduction. We further validate the proposed system by comparing its classification accuracy with some other methods on two brain imaging datasets for Alzheimer's disease (AD) progression studies. Our preliminary experimental results show that our algorithm achieves superior results on various classification tasks. Our work may enrich surface-based brain imaging research tools and potentially result in a diagnostic and prognostic indicator to be useful in individualized treatment strategies.

Improved Prediction of Imminent Progression to Clinically Significant Memory Decline Using Surface Multivariate Morphometry Statistics and Sparse Coding.

BACKGROUND: Besides their other roles, brain imaging and other biomarkers of Alzheimer's disease (AD) have the potential to inform a cognitively unimpaired (CU) person's likelihood of progression to mild cognitive impairment (MCI) and benefit subject selection when evaluating promising prevention therapies. We previously described that among baseline FDG-PET and MRI measures known to be preferentially affected in the preclinical and clinical stages of AD, hippocampal volume was the best predictor of incident MCI within 2 years (79%sensitivity/78%specificity), using standard automated MRI volumetric algorithmic programs, binary logistic regression, and leave-one-out procedures. OBJECTIVE: To improve the same prediction by using different hippocampal features and machine learning methods, cross-validated via two independent and prospective cohorts (Arizona and ADNI). METHODS: Patch-based sparse coding algorithms were applied to hippocampal surface features of baseline TI-MRIs from 78 CU adults who subsequently progressed to amnestic MCI in approximately 2 years ("progressors") and 80 matched adults who remained CU for at least 4 years ("nonprogressors"). Nonprogressors and progressors were matched for age, sex, education, and apolipoprotein E4 allele dose. We did not include amyloid or tau biomarkers in defining MCI. RESULTS: We achieved 92%prediction accuracy in the Arizona cohort, 92%prediction accuracy in the ADNI cohort, and 90%prediction accuracy when combining the two demographically distinct cohorts, as compared to 79%(Arizona) and 72%(ADNI) prediction accuracy using hippocampal volume. CONCLUSION: Surface multivariate morphometry and sparse coding, applied to individual MRIs, may accurately predict imminent progression to MCI even in the absence of other AD biomarkers.

Interaction Between BDNF Val66Met and APOE4 on Biomarkers of Alzheimer's Disease and Cognitive Decline.

BACKGROUND: Whether brain-derived neurotrophic factor (BDNF) Met carriage impacts the risk or progression of Alzheimer's disease (AD) is unknown. OBJECTIVE: To evaluate the interaction of BDNF Met and APOE4 carriage on cerebral metabolic rate for glucose (CMRgl), amyloid burden, hippocampus volume, and cognitive decline among cognitively unimpaired (CU) adults enrolled in the Arizona APOE cohort study. METHODS: 114 CU adults (mean age 56.85 years, 38% male) with longitudinal FDG PET, magnetic resonance imaging, and cognitive measures were BDNF and APOE genotyped. A subgroup of 58 individuals also had Pittsburgh B (PiB) PET imaging. We examined baseline CMRgl, PiB PET amyloid burden, CMRgl, and hippocampus volume change over time, and rate of change in cognition over an average of 15 years. RESULTS: Among APOE4 carriers, BDNF Met carriers had significantly increased amyloid deposition and accelerated CMRgl decline in regions typically affected by AD, but without accompanying acceleration of cognitive decline or hippocampal volume changes and with higher baseline frontal CMRgl and slower frontal decline relative to the Val/Val group. The BDNF effects were not found among APOE4 non-carriers. CONCLUSION: Our preliminary studies suggest that there is a weak interaction between BDNF Met and APOE4 on amyloid-ß plaque burden and longitudinal PET measurements of AD-related CMRgl decline in cognitively unimpaired late-middle-aged and older adults, but with no apparent effect upon rate of cognitive decline. We suggest that cognitive effects of BDNF variants may be mitigated by compensatory increases in frontal brain activity-findings that would need to be confirmed in larger studies.

Applying surface-based morphometry to study ventricular abnormalities of cognitively unimpaired subjects prior to clinically significant memory decline.

Ventricular volume (VV) is a widely used structural magnetic resonance imaging (MRI) biomarker in Alzheimer's disease (AD) research. Abnormal enlargements of VV can be detected before clinically significant memory decline. However, VV does not pinpoint the details of subregional ventricular expansions. Here we introduce a ventricular morphometry analysis system (VMAS) that generates a whole connected 3D ventricular shape model and encodes a great deal of ventricular surface deformation information that is inaccessible by VV. VMAS contains an automated segmentation approach and surface-based multivariate morphometry statistics. We applied VMAS to two independent datasets of cognitively unimpaired (CU) groups. To our knowledge, it is the first work to detect ventricular abnormalities that distinguish normal aging subjects from those who imminently progress to clinically significant memory decline. Significant bilateral ventricular morphometric differences were first shown in 38 members of the Arizona APOE cohort, which included 18 CU participants subsequently progressing to the clinically significant memory decline within 2 years after baseline visits (progressors), and 20 matched CU participants with at least 4 years of post-baseline cognitive stability (non-progressors). VMAS also detected significant differences in bilateral ventricular morphometry in 44 Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects (18 CU progressors vs. 26 CU non-progressors) with the same inclusion criterion. Experimental results demonstrated that the ventricular anterior horn regions were affected bilaterally in CU progressors, and more so on the left. VMAS may track disease progression at subregional levels and measure the effects of pharmacological intervention at a preclinical stage.

Impact of Zumba on Cognition and Quality of Life is Independent of APOE4 Carrier Status in Cognitively Unimpaired Older Women: A 6-Month Randomized Controlled Pilot Study.

OBJECTIVE: To investigate the association of a 6-month Zumba intervention with cognition and quality of life among older cognitively unimpaired apolipoprotein ∊4 (APOE4) carrier and noncarrier women. METHODS: Fifty-three women were randomly assigned to either twice-weekly Zumba group classes or maintenance of habitual exercise (control group) for 6 months. At baseline, 3, and 6 months, all participants underwent neuropsychological, physical activity, and quality-of-life assessments. RESULTS: Overall, neuropsychological test scores and level of physical activity did not differ between intervention and control groups at any time. However, compared to the control group, quality of life was higher at 3 months, and visuospatial working memory and response inhibition improved more in the intervention group by 6 months. Apolipoprotein ∊4 status did not affect the results. DISCUSSION: Zumba may strengthen performance on visuospatial working memory among cognitively unimpaired older women but this needs to be tested in a larger clinical trial.

Neuropsychological comparison of incident MCI and prevalent MCI.

INTRODUCTION: Little empirical work has been done to examine differences between mild cognitive impairment (MCI) diagnosed in research settings with longitudinal data (incident MCI) and MCI diagnosed in clinical settings (prevalent MCI). Because Alzheimer's disease progresses over a clinicopathological continuum, we examined the cognitive differences between these two different sources of MCI patients. METHODS: We compared 52 consecutively identified patients with prevalent amnestic MCI with 53 incident amnestic MCI participants from the Arizona APOE study. Neuropsychological data from common tests were compared encompassing four cognitive domains and one global indicator. RESULTS: Prevalent MCI cases performed significantly worse than incident MCI cases on global as well as domain-specific measures. DISCUSSION: By the time patients seek evaluation for memory loss, they have more severe single domain, amnestic MCI than research subjects with incident MCI. Studies of MCI should distinguish incident and prevalent not just single- and multiple-domain MCI.