Citations

Subjective cognitive decline (SCD) is prevalent in the general population, particularly among Hispanic adults. SCD increases the risk of mild cognitive impairment (MCI) and dementia. While non-pharmacologic interventions are recommended to mitigate cognitive decline and preserve daily function in SCD and MCI, such interventions are not readily available for Spanish-speaking Hispanic adults with SCD. This pilot study, preregistered at clinicialtrials.gov, aimed to develop a linguistically and culturally appropriate adaptation of an existing memory compensation intervention, the Memory Support System (MSS), from English to Spanish, and to gather data to assess its impact in this population. Twenty Spanish-speaking Hispanic adults with SCD and 16 support partners were recruited. Measures of treatment adherence, daily function, self-efficacy for memory, quality of life, mood, anxiety, and caregiver burden were assessed at baseline, treatment end, and 8-week follow-up. By treatment end, participants with SCD improved their general functional status, daily activities requiring organizational skills, and depression and anxiety symptoms. Partners reported improvement in anxiety by treatment end and in caregiver burden at follow-up. The MSS was successfully translated into Spanish and readily learned by participants with SCD and their partners. The MSS in Spanish may help with daily functioning and aspects of patient and family well-being.

Abstract The public health impact of genomic screening can be enhanced by cascade testing. However, cascade testing depends on communication of results to family members. While the barriers and facilitators of family communication have been researched following clinical genetic testing, the factors impacting the dissemination of genomic screening results are unknown. Using the pragmatic Electronic Medical Records and Genomics Network‐3 (eMERGE‐3) study, we explored the reported sharing practices of participants who underwent genomic screening across the United States. Six eMERGE‐3 sites returned genomic screening results for mostly dominant medically actionable disorders and surveyed adult participants regarding communication of results with first‐degree relatives. Across the sites, 279 participants completed a 1‐month and/or 6‐month post‐results survey. By 6 months, only 34% of the 156 respondents shared their results with all first‐degree relatives and 4% did not share with any. Over a third (39%) first‐degree relatives were not notified of the results. Half (53%) of participants who received their results from a genetics provider shared them with all first‐degree relatives compared with 11% of participants who received their results from a non‐genetics provider. The most frequent reasons for sharing were a feeling of obligation (72%) and that the information could help family members make medical decisions (72%). The most common reasons indicated for not sharing were that the family members were too young (38%), or they were not in contact (25%) or not close to them (25%). These data indicate that the professional returning the results may impact sharing patterns, suggesting that there is a need to continue to educate healthcare providers regarding approaches to facilitate sharing of genetic results within families. Finally, these data suggest that interventions to increase sharing may be universally effective regardless of the origin of the genetic result.

Abstract Purpose: The PARP inhibitor rucaparib is approved in the United States for patients with metastatic castration-resistant prostate cancer (mCRPC) and a deleterious germline and/or somatic BRCA1 or BRCA2 (BRCA) alteration. While sequencing of tumor tissue is considered the standard for identifying patients with BRCA alterations (BRCA+), plasma profiling may provide a minimally invasive option to select patients for rucaparib treatment. Here, we report clinical efficacy in patients with BRCA+ mCRPC identified through central plasma, central tissue, or local genomic testing and enrolled in TRITON2. Patients and Methods: Patients had progressed after next-generation androgen receptor–directed and taxane-based therapies for mCRPC and had BRCA alterations identified by central sequencing of plasma and/or tissue samples or local genomic testing. Concordance of plasma/tissue BRCA status and objective response rate and prostate-specific antigen (PSA) response rates were summarized. Results: TRITON2 enrolled 115 patients with BRCA+ identified by central plasma (n = 34), central tissue (n = 37), or local (n = 44) testing. Plasma/tissue concordance was determined in 38 patients with paired samples and was 47% in 19 patients with a somatic BRCA alteration. No statistically significant differences were observed between objective and PSA response rates to rucaparib across the 3 assay groups. Patients unable to provide tissue samples and tested solely by plasma assay responded at rates no different from patients identified as BRCA+ by tissue testing. Conclusions: Plasma, tissue, and local testing of mCRPC patients can be used to identify men with BRCA+ mCRPC who can benefit from treatment with the PARP inhibitor rucaparib.

AbstractStudies supporting a strong association between tau deposition and neuronal loss, neurodegeneration, and cognitive decline have heightened the allure of tau and tau‐related mechanisms as therapeutic targets. In February 2020, leading tau experts from around the world convened for the first‐ever Tau2020 Global Conference in Washington, DC, co‐organized and cosponsored by the Rainwater Charitable Foundation, the Alzheimer's Association, and CurePSP. Representing academia, industry, government, and the philanthropic sector, presenters and attendees discussed recent advances and current directions in tau research. The meeting provided a unique opportunity to move tau research forward by fostering global partnerships among academia, industry, and other stakeholders and by providing support for new drug discovery programs, groundbreaking research, and emerging tau researchers. The meeting also provided an opportunity for experts to present critical research‐advancing tools and insights that are now rapidly accelerating the pace of tau research.

Background: In Alzheimer’s disease and related disorders (ADRD) research, common outcome measures include cognitive and functional impairment, as well as persons with mild cognitive impairment (pwMCI) and care partner self-reported mood and quality of life. Studies commonly analyze these measures separately, which potentially leads to issues of multiple comparisons and/or multicollinearity among measures while ignoring the latent constructs they may be measuring. Objective: This study sought to examine the latent factor structure of a battery of 12-13 measures of domains mentioned above, used in a multicomponent behavioral intervention (The HABIT® program) for pwMCI and their partners. Methods: Exploratory factor analysis (EFA) involved 214 pwMCI-partner pairs. Subsequent Confirmatory factor analyses (CFA) used 730 pairs in both pre- and post-intervention conditions. Results: EFA generated a three-factor model. Factors could be characterized as partner adjustment (29.9%), pwMCI adjustment (18.1%), and pwMCI impairment (12.8%). The subsequent CFA confirmed our findings, and the goodness-of-fit for this model was adequate in both the pre- (CFI = 0.937; RMSEA = 0.057, p = 0.089) and post-intervention (CFI = 0.942; RMSEA = 0.051, p = 0.430) groups. Conclusion: Results demonstrated a stable factor structure across cohorts and intervention conditions suggesting that three broad factors may provide a straightforward and meaningful model to assess intervention outcome, at least during the MCI phase of ADRD.

Abstract Richter syndrome (RS) represents a transformation from chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) to aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL), which is associated with a dismal prognosis. Patients with DLBCL-RS have poor outcomes with DLBCL-directed therapy; thus, consolidation with hematopoietic cell transplantation (HCT) has been used, with durable remissions observed. Studies reporting HCT outcomes in patients with DLBCL-RS have been small, have not evaluated the prognostic impact of cytogenetic risk factors, and were conducted prior to the era of novel targeted therapy of CLL/SLL. We performed a Center for International Blood and Transplant Research registry study evaluating outcomes after autologous HCT (auto-HCT; n = 53) and allogeneic HCT (allo-HCT; n = 118) in patients with DLBCL-RS treated in the modern era. More auto-HCT recipients were in complete response (CR) at HCT relative to allo-HCT recipients (66% vs 34%), whereas a higher proportion of allo-HCT recipients had 17p deletion (33% vs 7%) and had previously received novel agents (39% vs 10%). In the auto-HCT cohort, the 3-year relapse incidence, progression-free survival (PFS), and overall survival (OS) were 37%, 48%, and 57%, respectively. Among allo-HCT recipients, the 3-year relapse incidence, PFS, and OS were 30%, 43%, and 52%, respectively. In the allo-HCT cohort, deeper response at HCT was associated with outcomes (3-year PFS/OS, 66%/77% CR vs 43%/57% partial response vs 5%/15% resistant; P < .0001 for both), whereas cytogenetic abnormalities and prior novel therapy did not impact outcomes. In our study, HCT resulted in durable remissions in therapy-sensitive patients with DLBCL-RS treated in the era of targeted CLL/SLL therapy, including patients with high-risk features.