Do current therapeutic anti-Aβ antibodies for Alzheimer’s disease engage the target?

Reducing amyloid-β peptide (Aβ) burden at the pre-symptomatic stages of Alzheimer’s disease (AD) is currently the advocated clinical strategy for treating this disease. The most developed method for targeting Aβ is the use of monoclonal antibodies including bapineuzumab, solanezumab and crenezumab. We have synthesized these antibodies and used surface plasmon resonance (SPR) and mass spectrometry to characterize and compare the ability of these antibodies to target Aβ in transgenic mouse tissue as well as human AD tissue. SPR analysis showed that the antibodies were able to bind Aβ with high affinity. All of the antibodies were able to bind Aβ in mouse tissue. However, significant differences were observed in human brain tissue. While bapineuzumab was able to capture a variety of N-terminally truncated Aβ species, the Aβ detected using solanezumab was barely above detection limits while crenezumab did not detect any Aβ. None of the antibodies were able to detect any Aβ species in human blood. Immunoprecipitation experiments using plasma from AD subjects showed that both solanezumab and crenezumab have extensive cross-reactivity with non-Aβ related proteins. Bapineuzumab demonstrated target engagement with brain Aβ, consistent with published clinical data. Solanezumab and crenezumab did not, most likely as a result of a lack of specificity due to cross-reactivity with other proteins containing epitope overlap. This lack of target engagement raises questions as to whether solanezumab and crenezumab are suitable drug candidates for the preventative clinical trials for AD.     

Interpersonal distress is associated with sleep and arousal in insomnia and good sleepers

Objective

The interpersonal environment is strongly linked to sleep. However, little is known about interpersonal distress and its association with sleep. We examined the associations among interpersonal distress, objective and subjective sleep in people with and without insomnia.

Methods

Participants in this cross-sectional observational study included men and women with insomnia (n = 28) and good sleeper controls (n = 38). Interpersonal distress was measured with the Inventory of Interpersonal Problems. Sleep parameters included insomnia severity, self-reported presleep arousal, and sleep quality; and polysomnographically-assessed sleep latency (SL), total sleep time (TST), wake after sleep onset (WASO), percent delta (stage 3 + 4 NREM), percent REM, and EEG beta power. Hierarchical linear regression was used to assess the relationship between distress from interpersonal problems and sleep and the extent to which relationships differed among insomnia patients and controls.

Results

More interpersonal distress was associated with more self-reported arousal and higher percentage of REM. More interpersonal distress was associated with greater insomnia severity and more cognitive presleep arousal for individuals with insomnia, but not for controls. Contrary to expectations, interpersonal distress was associated with shorter sleep latency in the insomnia group. Results were attenuated, but still significant, after adjusting for depression symptoms.

Conclusion

Distress from interpersonal problems is associated with greater self-reported arousal and higher percent REM. Individuals with insomnia who report more distress from interpersonal problems have greater insomnia severity and cognitive presleep arousal, perhaps due to rumination. These findings extend our knowledge of the association between interpersonal stressors and sleep. Assessment and consideration of interpersonal distress could provide a novel target for insomnia treatment.     

Improvement and Recovery from Eating Disorders: A Patient Perspective

This study presents a patient perspective on improvement and recovery from eating disorders. Forty-eight women recruited from patient organizations and a university eating disorder unit participated in the study. Participants completed standard questionnaires and a qualitative interview. "A wish to change," professional treatment, nonprofessional care, and important persons in the women's lives were identified as important recovery factors. Recovery included improved acceptance of oneself, interpersonal relations, problem solving, and body satisfaction, which was not entirely dependent on symptom absence. The patient perspective concurred with clinical reasoning about recovery.     

Environmental Factors Predictive of No-Show Visits in Radiology: Observations of Three Million Outpatient Imaging Visits Over 16 Years

PurposeTo evaluate the impact of environmental and socioeconomic factors on outpatient cancellations and “no-show visits” (NSVs) in radiology.Materials and MethodsWe conducted a retrospective analysis by collecting environmental factor data related to outpatient radiology visits occurring between 2000 and 2015 at our multihospital academic institution. Appointment attendance records were joined with daily weather observations from the National Oceanic and Atmospheric Administration and estimated median income from the US Census American Community Survey. A multivariate logistic regression model was built to examine relationships between NSV rate and median income, commute distance, maximum daily temperature, and daily snowfall.ResultsThere were 270,574 (8.0%) cancellations and 87,407 (2.6%) NSVs among 3,379,947 scheduled outpatient radiology appointments and 575,206 unique patients from 2000 to 2015. Overall cancellation rates decreased from 14% to 8%, and NSV rates decreased from 6% to 1% as median income increased from $20,000 to $120,000 per year. In a multivariate model, the odds of NSV decreased 10.7% per $10,000 increase in median income (95% confidence interval [CI]: 10.3%-11.1%) and 2.0% per 10°F increase in maximum daily temperature (95% CI: 1.3%-1.6%). The odds of NSV increased 1.4% per 10-mile increase in commute distance (95% CI: 1.3%-1.6%) and 4.5% per 1-inch increase in daily snowfall (95% CI: 3.6%-5.3%). Commute distance was more strongly associated with NSV for those in the two lower tertiles of income than the highest tertile (P < .001).ConclusionEnvironmental factors are strongly associated with patients’ attendance at scheduled outpatient radiology examinations. Modeling of appointment failure risk based on environmental features can help increase the attendance of outpatient radiology appointments.     

Brief Report: A Preliminary Study of the Relationship between Repetitive Behaviors and Concurrent Executive Function Demands in Children with Autism Spectrum Disorder

Journal of Autism and Developmental Disorders - The present study evaluated the hypothesis that the strength of the relationship between executive function (EF) and repetitive behaviors and...