Citations

Objectives: Compare speech perception performance growth and benchmark score achievement among adult cochlear implant (CI) recipients with single-sided deafness (SSD) versus bilateral moderate to profound hearing loss. Study Design: Retrospective matched cohort analysis. Setting: Tertiary referral center. Patients: Adults with SSD or bilateral moderate to profound hearing sensorineural hearing loss who underwent cochlear implantation from 2014 to 2019. Interventions: Cochlear implantation. Main outcome measures: Time-to-benchmark speech perception score (CNC, AzBio in quiet) and speech performance within first postoperative year. Results: Thirty-three SSD patients were matched to 66 bilateral hearing loss patients (referent cohort) for duration of deafness and preoperative ipsilateral CNC scores. Although SSD patients were more likely to achieve benchmark CNC scores more quickly compared with matched referents, this difference did not reach statistical significance (HR 1.72; 95% CI 0.78–3.82; p = 0.18). AzBio scores showed similar trends (HR 1.40; 95% CI 0.66–2.98; p = 0.38). At last follow-up, the SSD cohort had lower CNC (median 54% vs. 62%; p = 0.019) and AzBio scores (median 72% vs. 84%; p = 0.029) compared to the referent cohort. Conclusions: No significant difference in speech perception performance growth (i.e., time-to-benchmark speech perception score) was identified between SSD and bilateral hearing loss CI recipients, although patients with bilateral hearing loss achieved higher scores in the implanted ear within the first year of follow-up.

AbstractIntroductionHarboring two copies of the apolipoprotein E (APOE) ε2 allele strongly protects against Alzheimer's disease (AD). However, the effect of this genotype on gray matter (GM) volume in cognitively unimpaired individuals has not yet been described.MethodsMulticenter brain magnetic resonance images (MRIs) from cognitively unimpaired ε2 homozygotes were matched (1:1) against all other APOE genotypes for relevant confounders (n = 223). GM volumes of ε2 genotypic groups were compared to each other and to the reference group (APOE ε3/ε3).ResultsCarrying at least one ε2 allele was associated with larger GM volumes in brain areas typically affected by AD and also in areas associated with cognitive resilience. APOE ε2 homozygotes, but not APOE ε2 heterozygotes, showed larger GM volumes in areas related to successful aging.DiscussionIn addition to the known resistance against amyloid‐β deposition, the larger GM volumes in key brain regions may confer APOE ε2 homozygotes additional protection against AD‐related cognitive decline.

AbstractAs prevention trials advance with autosomal dominant Alzheimer disease (ADAD) participants, understanding the similarities and differences between ADAD and “sporadic” late‐onset AD (LOAD) is critical to determine generalizability of findings between these cohorts. Cognitive trajectories of ADAD mutation carriers (MCs) and autopsy‐confirmed LOAD individuals were compared to address this question. Longitudinal rates of change on cognitive measures were compared in ADAD MCs (n = 310) and autopsy‐confirmed LOAD participants (n = 163) before and after symptom onset (estimated/observed). LOAD participants declined more rapidly in the presymptomatic (preclinical) period and performed more poorly at symptom onset than ADAD participants on a cognitive composite. After symptom onset, however, the younger ADAD MCs declined more rapidly. The similar but not identical cognitive trajectories (declining but at different rates) for ADAD and LOAD suggest common AD pathologies but with some differences.

Objectives/Hypothesis To review hearing preservation after microsurgical resection of sporadic vestibular schwannomas according to tumor size. Study Design Retrospective cohort. Methods Baseline, intraoperative, and postoperative patient and tumor characteristics were retrospectively collected for a cohort who underwent hearing preservation microsurgery. Serviceable hearing was defined by a pure tone average ≤50 dB and word recognition score ≥50%. Results A total of 243 patients had serviceable hearing preoperatively. Fifty (21%) tumors were confined to the internal auditory canal, and the median tumor size was 16.2 mm (interquartile range [IQR] 11.3–23.2) for tumors with cerebellopontine angle extension. Serviceable hearing was maintained in 64% of patients with tumors confined to the internal auditory canal, 28% with cerebellopontine angle extension <15 mm, and 9% with cerebellopontine angle extension ≥15 mm. On multivariable analysis, the odds ratios of acquiring nonserviceable hearing postoperatively for tumors extending <15 mm and ≥15 mm into the cerebellopontine angle were 5.75 (95% confidence interval [CI] 2.13–15.53; P < .001) and 22.11 (95% CI 7.04–69.42; P < .001), respectively, compared with intracanalicular tumors. Conclusions The strongest predictor of hearing preservation with microsurgery after multivariable adjustment is tumor size. Approximately 10% of patients with tumors ≥15 mm of cerebellopontine angle extension will retain serviceable hearing after microsurgery. Furthermore, hearing preservation techniques offer cochlear nerve preservation and cochlear patency allowing for possible future cochlear implantation. An attempt at hearing preservation, including avoiding surgical approaches that necessarily sacrifice hearing, is worthwhile even in larger tumors if serviceable hearing is present preoperatively. Level of Evidence 4 Laryngoscope , 132:1657–1664, 2022

Abstract Background Detecting copy number variations (CNVs) and copy number alterations (CNAs) based on whole-genome sequencing data is important for personalized genomics and treatment. CNVnator is one of the most popular tools for CNV/CNA discovery and analysis based on read depth. Findings Herein, we present an extension of CNVnator developed in Python—CNVpytor. CNVpytor inherits the reimplemented core engine of its predecessor and extends visualization, modularization, performance, and functionality. Additionally, CNVpytor uses B-allele frequency likelihood information from single-nucleotide polymorphisms and small indels data as additional evidence for CNVs/CNAs and as primary information for copy number–neutral losses of heterozygosity. Conclusions CNVpytor is significantly faster than CNVnator—particularly for parsing alignment files (2–20 times faster)—and has (20–50 times) smaller intermediate files. CNV calls can be filtered using several criteria, annotated, and merged over multiple samples. Modular architecture allows it to be used in shared and cloud environments such as Google Colab and Jupyter notebook. Data can be exported into JBrowse, while a lightweight plugin version of CNVpytor for JBrowse enables nearly instant and GUI-assisted analysis of CNVs by any user. CNVpytor release and the source code are available on GitHub at https://github.com/abyzovlab/CNVpytor under the MIT license.

Longitudinal observational cohort studies are being conducted worldwide to understand cognition, biomarkers, and the health of the aging population better. Cross-cohort comparisons and networks of registries in Alzheimer’s disease (AD) foster scientific exchange, generate insights, and contribute to the evolving clinical science in AD. A scientific working group was convened with invited investigators from established cohort studies in AD, in order to form a research collaboration network as a resource to address important research questions. The Connecting Cohorts to Diminish Alzheimer’s Disease (CONCORD-AD) collaboration network was created to bring together global resources and expertise, to generate insights and improve understanding of the natural history of AD, to inform design of clinical trials in all disease stages, and to plan for optimal patient access to disease-modifying therapies once they become available. The network brings together expertise and data insights from 7 cohorts across Australia, Europe, and North America. Notably, the network includes populations recruited through memory clinics as well as population-based cohorts, representing observations from individuals across the AD spectrum. This report aims to introduce the CONCORD-AD network, providing an overview of the cohorts involved, reporting the common assessments used, and describing the key characteristics of the cohort populations. Cohort study designs and baseline population characteristics are compared, and available cognitive, functional, and neuropsychiatric symptom data, as well as the frequency of biomarker assessments, are summarized. Finally, the challenges and opportunities of cross-cohort studies in AD are discussed.