Stonnington, Cynthia M.

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.

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.

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.

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-β 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.

AbstractBackgroundPhiladelphia chromosome negative myeloproliferative neoplasms (MPNs), including essential thrombocythemia, polycythemia vera, and myelofibrosis, have severe function‐limiting symptom burden that is experienced by the majority of patients. Previous studies have suggested that depression may be present in over a quarter of MPN patients, but to date no studies have evaluated the relationship between depression and other variables such as symptoms.MethodsA 70‐item internet based survey regarding fatigue and mood symptoms was developed by a multidisciplinary team of MPN investigators, patients and patient advocates including Patient Health Questionnaire and the Myeloproliferative Neoplasm Symptom Assessment Form was completed by over 1300 patients with MPN diagnosis.ResultsThere were 309 respondents (23%) with PHQ‐2 scores ≥ 3. In this analysis, we found worse systemic symptom burden in individuals reporting depressive symptoms.ConclusionThis analysis suggests the importance of depression in contributing to as well as confounding symptomatology in MPN patients, and suggests that this critical variable should also be addressed by clinicians and researchers alike when comprehensively assessing symptom burden etiologies.

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.

AbstractIntroductionLittle 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.MethodsWe 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.ResultsPrevalent MCI cases performed significantly worse than incident MCI cases on global as well as domain‐specific measures.DiscussionBy 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.

Background: Brain imaging measurements can provide evidence of possible preclinical Alzheimer’s disease (AD). Their ability to predict individual imminent clinical conversion remains unclear. Objective: To investigate the ability of pre-specified volumetric magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET) measurements to predict which cognitively unimpaired older participants would subsequently progress to amnestic mild cognitive impairment (aMCI) within 2 years. Methods: From an apolipoprotein E4 (APOE4) enriched prospective cohort study, 18 participants subsequently progressed to the clinical diagnosis of aMCI or probable AD dementia within 1.8±0.8 years (progressors); 20 participants matched for sex, age, education, and APOE allele dose remained cognitively unimpaired for at least 4 years (nonprogressors). A complementary control group not matched for APOE allele dose included 35 nonprogressors. Groups were compared on baseline FDG-PET and MRI measures known to be preferentially affected in the preclinical and clinical stages of AD and by voxel-wise differences in regional gray matter volume and glucose metabolism. Receiver Operating Characteristic, binary logistic regression, and leave-one-out procedures were used to predict clinical outcome for the a priori measures. Results: Compared to non-progressors and regardless of APOE-matching, progressors had significantly reduced baseline MRI and PET measurements in brain regions preferentially affected by AD and reduced hippocampal volume was the strongest predictor of an individual’s imminent progression to clinically significant memory decline (79% sensitivity/78% specificity among APOE-matched cohorts). Conclusion: Regional MRI and FDG-PET measurements may be useful in predicting imminent progression to clinically significant memory decline.