Amyloid positron emission tomography candidates may focus more on benefits than risks of results disclosure

IntroductionGiven mounting calls to disclose biomarker test results to research participants, we explored factors underlying decisions by patients with mild cognitive impairment to receive amyloid imaging results.MethodsProspective, qualitative interviews were conducted with 59 participants (30 = mild cognitive impairment patients, 29 = care partners) from the scan arm of a randomized controlled trial on the effects of amyloid PET results disclosure in an Alzheimer Disease Research Center setting.ResultsSixty‐three percent of the participants were female, with an average age of 72.9 years, and most had greater than a high school level of education (80%). Primary motivations included: (1) better understanding one’s mild cognitive impairment etiology and prognosis to plan ahead, and (2) learning one’s brain amyloid status for knowledge’s sake, regardless of whether the information is actionable. Most participants demonstrated an adequate understanding of the scan’s limitations, yet instances of characterizing amyloid PET as a definitive test for Alzheimer’s disease occurred. Mention of potential drawbacks, such as negative psychological outcomes, was minimal, even among care partners.DiscussionFindings demonstrate a risk of disproportionate focus on possible benefits of testing among amyloid scan candidates and suggest a need to clearly emphasize the limitations of amyloid PET when counseling cognitively impaired patients and their families before testing. Future research should examine whether minimizing drawbacks at the pre‐imaging stage has adverse consequences on results disclosure.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152635/1/dad2jdadm201805003.pd

Forgotten Women: Incarceration and Health Concerns of Minority Women

Paper Presentatio

Two-period linear mixed effects models to analyze clinical trials with run-in data when the primary outcome is continuous: Applications to Alzheimer\u27s disease.

Introduction: Study outcomes can be measured repeatedly based on the clinical trial protocol before randomization during what is known as the run-in period. However, it has not been established how best to incorporate run-in data into the primary analysis of the trial. Methods: We proposed two-period (run-in period and randomization period) linear mixed effects models to simultaneously model the run-in data and the postrandomization data. Results: Compared with the traditional models, the two-period linear mixed effects models can increase the power up to 15% and yield similar power for both unequal randomization and equal randomization. Discussion: Given that analysis of run-in data using the two-period linear mixed effects models allows more participants (unequal randomization) to be on the active treatment with similar power to that of the equal-randomization trials, it may reduce the dropout by assigning more participants to the active treatment and thus improve the efficiency of AD clinical trials

Sociosexuality, testosterone, and life history status: Prospective associations and longitudinal changes among men in Cebu, Philippines

Sociosexuality is defined as an individual\u27s interest in uncommitted sexual activity and can be measured in terms of both psychological orientations and behavioral expression. In socio-ecological contexts in which adults monogamously partner and cooperate to raise children, individuals with unrestricted sociosexuality are likely to prioritize mating/competition over committed partnering and parenting. Given the importance of mother-father cooperation in the evolutionary past, humans may have the capacity to facultatively and opportunistically downregulate sociosexuality to focus on priorities related to invested partnering and parenting. To date, no prior studies have used longitudinal data to track within-individuals changes in sociosexuality as it relates to such life history transitions. Given the lack of prior longitudinal research in this area, it is likewise unknown what physiological mechanisms might mediate within-individual changes in sociosexuality through time but testosterone is a plausible candidate. To explore these questions, we drew on a large, long-running study of Filipino men (n=288), who were single non-fathers at 25.9 years of age and were followed up 4–5 years later. We found that men with more unrestricted sociosexuality at baseline were more likely to experience relationship dissolution by follow-up, consistent with past work. Compared to men who remained single non-fathers at follow-up, men who became married residential fathers showed shifts towards more restricted global sociosexuality as well as sociosexual behavior. Relative to their own baseline values, married residential fathers also had more restricted sociosexuality in all domains at follow-up. They were the only group for whom this was found. We found theoretically-consistent but modest support for positive correlations between men\u27s testosterone and their sociosexuality, but no evidence that the two change in tandem together through time. Our results suggest that some amount of between-individual differences in sociosexuality are not stable and can facultatively shift alongside other aspects of male reproductive effort

Tau accumulation in autosomal dominant Alzheimer\u27s disease: A longitudinal [18F]flortaucipir study

Cortical tau accumulation is a key pathological event that partly defines Alzheimer\u27s disease (AD) onset and is associated with cognitive decline and future disease progression. However, an improved understanding of the timing and pattern of early tau deposition in AD and how this may be tracked in vivo is needed. Data from 59 participants involved in two longitudinal cohort studies of autosomal dominant AD (ADAD) were used to investigate whether tau PET can detect and track presymptomatic change; seven participants were symptomatic, and 52 were asymptomatic but at a 50% risk of carrying a pathogenic mutation. All had baseline flortaucipir (FTP) PET, MRI and clinical assessments; 26 individuals had more than one FTP PET scan. Standardised uptake value ratios (SUVRs) in prespecified regions of interest (ROIs) were obtained using inferior cerebellar grey matter as the reference region. We compared the changes in FTP SUVRs between presymptomatic carriers, symptomatic carriers and non-carriers, adjusting for age, sex and study site. We also investigated the relationship between regional FTP SUVRs and estimated years to/from symptom onset (EYO). Compared to both non-carriers and presymptomatic carriers, FTP SUVRs were significantly higher in symptomatic carriers in all ROIs tested (p \u3c 0.001). There were no significant regional differences between presymptomatic carriers and non-carriers in FTP SUVRs, or their rates of change (p \u3e 0.05), although increased FTP signal uptake was seen posteriorly in some individuals around the time of expected symptom onset. When we examined the relationship of FTP SUVR with respect to EYO, the earliest significant regional difference between mutation carriers and non-carriers was detected within the precuneus prior to estimated symptom onset in some cases. This study supports preliminary studies suggesting that presymptomatic tau tracer uptake is rare in ADAD. In cases where early uptake was seen, there was often a predilection for posterior regions (the precuneus and post-cingulate) as opposed to the medial temporal lobe, highlighting the importance of examining in vivo tau uptake beyond the confines of traditional Braak staging

The Roles of Vertical Advection and Eddy Diffusion in the Equatorial Mesospheric Semi-Annual Oscillation (MSAO)

Observations of the mesospheric semi-annual oscillation (MSAO) in the equatorial region have been reported dating back several decades. Seasonal variations in both species densities and airglow emissions are well documented. The extensive observations available offer an excellent case study for comparison with model simulations. A broad range of MSAO measurements is summarised with emphasis on the 80-100 km region. The objective here is not to address directly the complicated driving forces of the MSAO, but rather to employ a combination of observations and model simulations to estimate the limits of some of the underlying dynamical processes. Photochemical model simulations are included for near-equinox and near-solstice conditions, the two times with notable differences in the observed MSAO parameters. Diurnal tides are incorporated in the model to facilitate comparisons of observations made at different local times. The roles of water vapour as the driver species and ozone as the response species are examined to test for consistency between the model results and observations. The simulations suggest the interactions between vertical eddy diffusion and background vertical advection play a significant role in the MSAO phenomenon. Further, the simulations imply there are rigid limits on vertical advection rates and eddy diffusion rates. For August at the Equator, 90 km altitude, the derived eddy diffusion rate is approximately 1 x 106 cm2 s-1 and the vertical advection is upwards at 0.8 cm s-1. For April the corresponding values are 4 x 105 cm2 s-1 and 0.1 cm s-1. These results from the current 1-D model simulations will need to be verified by a full 3-D simulation. Exactly how vertical advection and eddy diffusion are related to gravity wave momentum as discussed by Dunkerton (1982) three decades ago remains to be addressed

Slow early growers have more muscle in relation to adult activity: evidence from Cebu, Philippines

Adult skeletal muscle mass (SMM) protects against type 2 diabetes but little is known about its developmental antecedents. We examined whether pace of early weight gain predicted adult SMM in a birth cohort from Cebu City, Philippines. Additionally, we examined whether increases in SMM associated with adult muscle-building exercise varied according to early growth

Lecanemab in patients with early Alzheimer\u27s disease: Detailed results on biomarker, cognitive, and clinical effects from the randomized and open-label extension of the phase 2 proof-of-concept study

BACKGROUND: Lecanemab, a humanized IgG1 monoclonal antibody that targets soluble aggregated Aβ species (protofibrils), has demonstrated robust brain fibrillar amyloid reduction and slowing of clinical decline in early AD. The objective of this analysis is to report results from study 201 blinded period (core), the open-label extension (OLE), and gap period (between core and OLE) supporting the effectiveness of lecanemab. METHODS: The lecanemab study 201 core was a double-blind, randomized, placebo-controlled study of 856 patients randomized to one of five dose regimens or placebo. An OLE of study 201 was initiated to allow patients to receive open-label lecanemab 10mg/kg biweekly for up to 24 months, with an intervening off-treatment period (gap period) ranging from 9 to 59 months (mean 24 months). RESULTS: At 12 and 18 months of treatment in the core, lecanemab 10 mg/kg biweekly demonstrated dose-dependent reductions of brain amyloid measured PET and corresponding changes in plasma biomarkers and slowing of cognitive decline. The rates of clinical progression during the gap were similar in lecanemab and placebo subjects, with clinical treatment differences maintained after discontinued dosing over an average of 24 months in the gap period. During the gap, plasma Aβ42/40 ratio and p-tau181 levels began to return towards pre-randomization levels more quickly than amyloid PET. At OLE baseline, treatment differences vs placebo at 18 months in the randomized period were maintained across 3 clinical assessments. In the OLE, lecanemab 10 mg/kg biweekly treatment produced dose-dependent reductions in amyloid PET SUVr, improvements in plasma Aβ42/40 ratio, and reductions in plasma p-tau181. CONCLUSIONS: Lecanemab treatment resulted in significant reduction in amyloid plaques and a slowing of clinical decline. Data indicate that rapid and pronounced amyloid reduction correlates with clinical benefit and potential disease-modifying effects, as well as the potential to use plasma biomarkers to monitor for lecanemab treatment effects. TRIAL REGISTRATION: ClinicalTrials.gov NCT01767311

Centerscope

Centerscope, formerly Scope, was published by the Boston University Medical Center "to communicate the concern of the Medical Center for the development and maintenance of improved health care in contemporary society.