Citations

Abstract Introduction Remote cognitive assessments offer an accessible, scalable way to support clinical characterization and longitudinal monitoring of cognition. This study evaluates the feasibility of implementing Mayo Test Drive (MTD), a remote, self-administered digital cognitive assessment, within a specialized clinic focused on eligibility assessments for anti-amyloid therapies for Alzheimer’s disease (AD). Method Two-hundred and nine ( N =209) patients (M age =71.2, 53% female) were evaluated through the Mayo Clinic Rochester Alzheimer’s Disease Treatment Clinic (ADTC) and had the opportunity to complete MTD, either as a remote, patient-initiated session through a patient-facing healthcare portal or during an in-clinic neuropsychological evaluation. Results Clinical diagnoses included 55.2% mild cognitive impairment (MCI), 31.0% mild dementia, and 11.6% moderate dementia, in addition to 2.2% cognitively unimpaired (CU), as determined by neurology consensus at a multidisciplinary case conference. Among those who initiated MTD ( n =197/209), 97.5% completed a session (70.6% remotely, 26.9% in clinic). Completion rates were high across diagnostic groups and did not significantly differ by clinical severity ( p =.12): CU (100%), MCI (99.1%), mild dementia (97.0%), and moderate dementia (89.5%). Remote completion rates overall were high (97.9%). Among completers, administration setting (remote vs. in-clinic) did not significantly differ by clinical stage, χ²(3)=2.37, p =.49. Reasons for non-initiation included not receiving or opening portal messages and other/unknown factors. Discussion Remote digital cognitive assessment is feasible within the context of clinic eligibility evaluations for AD therapies. The high completion rates of MTD across clinical impairment levels in this setting support development of paths for broader use in cognitive characterization in AD care.

Abstract BCMA-directed CAR T-cell and T-cell engager (TCE) therapies produce high response rates in relapsed multiple myeloma, yet most patients progress. Prior work identified TNFRSF17 alterations mediating antigen escape in up to 43% of TCE progressions. To evaluate the generalizability of these findings and examine antigen-loss-independent resistance, we performed whole-exome sequencing on 32 paired pre- and post-treatment progression bone marrow samples from 15 patients (5 CAR T, 10 TCE); two patients received both agents. TNFRSF17 alterations were infrequent and restricted to TCE recipients (one concurrent frameshift and missense mutation; two heterozygous copy-number losses); no biallelic loss or CAR T-associated events were observed. In contrast, deleterious/loss-of-function variants in NF-κB, PI3K-AKT-mTOR, and MAPK/ERK pathways were universal in pre-treatment samples and acquired or clonally enriched in 80% of patients at progression. Acquired events included loss-of-function alterations in CYLD , activating mutations in KRAS , NRAS and BRAF , and acquired TP53 mutations. In this series, antigen escape via TNFRSF17 /BCMA alteration was uncommon. Instead, pre-existing, acquired and clonally enriched pathogenic variants in NF-κB, PI3K-AKT-mTOR and MAPK cascades, together with TP53 mutation, emerged as a frequent finding. These alterations suggest that deregulation of BCMA-downstream survival signaling, enhanced proliferative fitness, and elevation of apoptotic threshold constitute antigen-loss-independent mechanisms of resistance.

Objectives: Pulmonary function tests (PFTs) are essential for diagnosis, management, and follow-up of a wide range of respiratory conditions as they provide quantitative insights into various aspects of lung function. Precision in ordering and scheduling PFTs, like any test, is crucial as errors can lead to misdiagnoses, delayed treatments, unnecessary retesting, inflated healthcare costs, and potentially compromised patient care. Hence, the aim of this quality improvement initiative was to reduce the PFT ordering error rate to below 5% by redesigning the ordering workflow and implementing a standardized order set tailored to specific clinical scenarios. Methods: The quality improvement initiative was implemented from August 2023 to March 2024. Data was collected from the electronic medical record (EMR) using predefined operational definitions to identify incorrect PFT orders and scheduling errors. A redesigned orderset was created to align with specific clinical presentations, including symptoms, suspected diagnosis, confirmed diagnosis, and presurgical evaluation. Scheduling was also restructured to match the expected testing time for each category. Education sessions were conducted with ordering providers, and ongoing feedback loops were established. Results: Among 575 preintervention PFT orders, 130 (22.6%) contained errors. Following implementation, review of 607 postintervention orders showed a reduction in error rates to 4.1%, representing an ∼80% improvement ( P <0.01). There was no increase in unnecessary testing, supporting the effectiveness of the intervention without unintended negative consequences. Conclusions: Implementation of a knowledge-based CDSS with standardized order sets significantly reduced PFT ordering errors and variability, improving guideline adherence and care quality. Continued refinement and integration with evolving technologies are essential for broader applicability.

Odontogenic myxoma (OM) is an uncommon, locally aggressive odontogenic neoplasm with characteristic histologic and clinico-radiographic features but with potential for histologic overlap with other odontogenic and non-odontogenic entities and a non-specific immunoprofile. Widespread loss of heterozygosity (LOH) has been recently described in rare cases of OM. The aim of this study was to determine whether widespread LOH represents a recurrent molecular signature that can be leveraged for clinical decision-making. Allele-specific copy number variation data from chromosomal microarray were generated from 7 OM, comprising a combined prospective and retrospective cohort. Four tumors arose in the mandible and 3 in the maxilla in patients ranging in age from 18 to 94 years (median: 44), with tumor size ranging from 2.2 to 13.0 cm. Variable amounts of fibrous stroma (odontogenic “fibromyxoma”) were present in 4/7 OM, and hypercellularity not typically appreciated in conventional OM was present in 3/7 cases. All OM (7/7) demonstrated widespread LOH, with 5 cases showing a near-haploid/low hypodiploid genomes (multiple monosomies) and 2 cases showing evidence of pseudo-hyperdiploidy due to probable endoreduplication. Both pseudo-hyperdiploid cases were ≥10 cm in size; 1 represented local recurrence. Chromosomes 1 to 3, 6, 9, 11, 13, 15, and 22 demonstrated LOH in ≥75% of cases (chromosomes 1 to 3, 6, and 9 in 100% of cases), while chromosomes 5, 12, 19, and 20 universally retained heterozygosity. Altogether, widespread LOH is a recurrent event in OM and a novel finding in odontogenic pathology, and allele-specific copy number variation analysis can serve as a diagnostic adjunct in challenging cases.

Background Parkinson's disease (PD) typically presents after age 60; however, approximately 10% of individuals experience early-onset PD (EOPD), with symptoms beginning between ages 21 and 50. Beyond motor and non-motor symptoms, PD can impact personal relationships through stigma, social isolation, and emotional burden. This study aims to examine the influence of PD on relationship outcomes such as divorce or separation. Methods This exploratory study analyzed data from the Fox Insight cohort, an online longitudinal research initiative supported by The Michael J. Fox Foundation. We included 470 individuals with self-reported PD who had complete data on marital status (“married” or “divorced”) and age at PD onset. Participants were categorized as having EOPD (<50 years) or late-onset PD (≥50 years). Chi-square tests assessed the association between PD onset group and marital status. A binary logistic regression model further evaluated gender and onset age as predictors of marital status in a subset of 330 participants. Results A significant association was found between PD onset group and marital status, with a higher divorce rate among the EOPD group (17.5%; 7/40) compared to late-onset PD (6.1%; 26/430) (p = 0.017). Logistic regression revealed no statistically significant predictors, though trends suggested lower odds of divorce in men and those with late-onset PD. Conclusion This exploratory analysis identified a potential association between early PD onset and higher divorce rates; however, with only 7 events in 40 EOPD participants, this finding is inherently unstable and should be regarded as hypothesis-generating only. Confirmation in larger, longitudinal cohorts is required before any conclusions can be drawn.

Importance Cerebral hemodynamic impairment in patients with asymptomatic internal carotid artery (ICA) stenosis is associated with reduced cognition. It is uncertain whether revascularization might be an effective treatment for cognitive impairment in these patients. Objective To test whether any cognitive benefit from revascularization of high-grade, asymptomatic ICA stenosis varies based on the degree of baseline cerebral hemodynamic impairment. Design, Setting, and Participants This substudy was conducted within a multicenter phase 3 randomized clinical trial. Adults (aged 35-86 years) without dementia with eighth-grade education or higher and unilateral asymptomatic ICA stenosis greater than or equal to 70% were enrolled from January 2018 to July 2024 at 61 sites in North America (last follow-up in July 2025). Of 607 participants screened from 2485 in CREST-2, 392 were enrolled. Magnetic resonance or computed tomographic perfusion imaging tested for baseline hemodynamic impairment defined by delayed time-to-peak (TTP) arrival of intravenous contrast in the hemisphere ipsilateral minus contralateral to the stenotic artery. Intervention Carotid revascularization (endarterectomy or stenting) plus intensive medical management (IMM) vs IMM alone. Main Outcomes and Measures The primary outcome was the difference in composite cognitive z score over 1 year based on 5 cognitive tests. The primary analysis tested for an interaction between treatment group (revascularization vs IMM alone) and degree of baseline hemodynamic impairment among those with reduced baseline cognition (cognitive z score ≤−1.0 SD). Results Of 392 participants enrolled (mean age, 71 years; 125 [32%] females), 61 were excluded for missing baseline imaging and 40 for missing cognitive examinations or other covariates, leaving 291 with complete data. Fifty-one had reduced cognition at baseline (25 in the revascularization group and 26 in the IMM alone group). TTP ranged from no interhemispheric TTP delay to a more-than-2-second delay. Mean (SD) cognitive z scores were −1.36 (0.51) at baseline and −1.17 (0.47) at 1 year in the revascularization group and −1.34 (0.83) at baseline and −1.01 (0.97) at 1 year in the IMM alone group. The primary analysis showed no difference in cognition by treatment group over 1 year, adjusting for treatment group × hemodynamic status interaction and other covariates (adjusted difference in cognitive z score, −0.15 SD [95% CI, −0.54 to 0.24]). The interaction was not significant (β estimate = 0.018 [95% CI, −0.025 to 0.061]; P = .40). Conclusions and Relevance In this substudy of a randomized clinical trial, there was no differential effect of revascularization vs IMM alone on cognition over 1 year by cerebral hemodynamic status among those with baseline reduced cognition, suggesting that revascularization does not improve cognitive dysfunction by restoring flow to the brain in chronic asymptomatic carotid stenosis. Trial Registration ClinicalTrials.gov Identifier: NCT03121209

ABSTRACT Aim To systematically review and meta‐analyze cohort studies evaluating associations of gingival inflammation, periodontitis, and tooth loss with cognitive decline and incident mild cognitive impairment or dementia. Methods PROSPERO‐registered searches of MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Library identified cohort studies from inception through October 10, 2025, with a PubMed update on June 24, 2026. Random‐effects meta‐analyses pooled adjusted hazard ratios (HRs) for dementia/MCI; cognitive function outcomes were summarized qualitatively. Risk of bias (RoB) was assessed using the Newcastle–Ottawa Scale. Results Fifty‐nine studies met inclusion criteria; 28 contributed to dementia/MCI meta‐analyses. Severe periodontitis (HR: 1.16; 95% CI: 1.06–1.27; I 2 = 0%; Q ‐test p = 0.49), periodontitis of unspecified severity (HR: 1.45; 95% CI: 1.21–1.73; I 2 = 98%; Q ‐test p < 0.001), edentulism (HR: 1.26; 95% CI: 1.19–1.33), and low tooth count (HR: 1.27; 95% CI: 1.14–1.42; I 2 = 94%; Q ‐test p < 0.001) were associated with elevated dementia/MCI risk. RoB was low in 31 studies (53%), moderate in 25 (42%), and high in 3 (5%); inadequate confounder adjustment was common. Meta‐regression showed stronger estimates for ICD‐code periodontitis definitions (fold change (FC) = 1.44 95% CI: 1.04–2.01), older cohorts (FC per year = 1.02 95% CI: 1.00, 1.05), and weaker estimates with lower RoB (FC per NOS star = 0.81 95% CI: 0.73–0.92). Follow‐up duration, cohort age, and RoB were not associated with tooth‐count estimates. Conclusion Periodontitis and tooth loss are associated with modestly higher dementia/MCI risk and poorer cognitive function, but heterogeneity, residual confounding, and bias temper causal interpretation. Longitudinal studies with rigorous baseline cognition assessment and intervention studies are needed.

BACKGROUND Hypertrophic olivary degeneration (HOD) is a rare form of transsynaptic degeneration caused by disruption of the dentato-rubro-olivary pathway (Guillain-Mollaret triangle). It is most described following surgical intervention or acute hemorrhagic injury affecting that pathway. However, longitudinal imaging documenting the natural progression of HOD in patients with brainstem cerebral cavernous malformations (CCMs) remains sparsely described at the individual patient level. OBSERVATIONS The authors present the case of a 70-year-old woman with a pontine CCM followed longitudinally over 4 years. Initial imaging demonstrated a right-sided pontine lesion with unilateral HOD in the absence of symptoms. Over time, the CCM enlarged and extended across the midline, coinciding with the development of bilateral HOD and delayed onset of gait imbalance and palatal myoclonus. No surgical intervention was performed. LESSONS In this case, the radiographic evolution from unilateral to bilateral involvement occurred concurrently with the delayed clinical manifestation of HOD. https://thejns.org/doi/10.3171/CASE26577