Citations

Abstract INTRODUCTION Early‐onset Alzheimer's disease (EOAD) manifests prior to the age of 65, and affects 4%–8% of patients with Alzheimer's disease (AD). The current analyses sought to examine longitudinal cognitive trajectories of participants with early‐onset dementia. METHODS Data from 307 cognitively normal (CN) volunteer participants and those with amyloid‐positive EOAD or amyloid‐negative cognitive impairment (EOnonAD) were compared. Cognitive trajectories across a comprehensive cognitive battery spanning 42 months were examined using mixed‐effects modeling. RESULTS The EOAD group displayed worse cognition at baseline relative to EOnonAD and CN groups, and more aggressive declines in cognition over time. The largest effects were observed on measures of executive functioning domains, while memory declines were blunted in EOAD. DISCUSSION EOAD declined 2–4× faster than EOnonAD, and EOAD pathology is not restricted to memory networks. Early identification of deficits is critical to ensure that individuals with sporadic EOAD can be considered for treatment using disease‐modifying medications. Highlights Represents the most comprehensive longitudinal characterization of sporadic EOAD to date. The trajectory of cognitive declines was steep for EOAD participants and worse than for other groups. Executive functioning measures exhibited the greatest declines over time in EOAD.

The rise in liver disease incidence and prevalence has led to increasing morbidity and mortality worldwide. Persistent hepatic inflammation drives disease progression by increasing fibrosis, advancing to cirrhosis, and potentially developing into hepatocellular carcinoma (HCC). Addressing these complications is essential to reduce liver-related mortality. Recent studies suggest that non-steroidal anti-inflammatory drugs, particularly aspirin, may play a beneficial role in managing liver disease. Aspirin’s anti-inflammatory and chemoprotective effects contribute to slowing disease progression and reducing the risks associated with chronic liver disease (CLD). This review highlights the current literature on the effects of aspirin in CLD, with a focus on patients with metabolic-associated steatotic liver disease (MASLD) and hepatitis B and C. We will examine aspirin’s potential ability to mitigate fibrosis, reduce the incidence of HCC, and lower liver-related mortality. Additionally, we will discuss its potential side effects and safety considerations, particularly in the context of liver disease, where there is an increased risk of bleeding.

Abstract INTRODUCTION Premenopausal bilateral oophorectomy (PBO) before the age of 46 years is associated with an increased risk of dementia. We investigated the long‐term effects of PBO performed before age 50 years on amyloid beta (Aβ), tau, and neurodegeneration imaging biomarkers of Alzheimer's disease (AD). METHODS Mayo Clinic Cohort Study of Oophorectomy and Aging‐2 participants were divided into early PBO (< 46 years; n = 61), and late PBO (46–49 years; n = 51) groups and were compared to referent women who did not undergo PBO ( n = 119). RESULTS Early PBO was associated with thinner entorhinal cortex ( p = 0.014), higher tau load at higher levels of Aβ load ( Pp = 0.005), higher Aβ load ( p = 0.026), and smaller temporal lobe cortical thickness ( p = 0.022), only at older ages compared to the referent group. DISCUSSION PBO before the age of 46 years is associated with entorhinal cortex thinning, elevated tau at higher Aβ levels, along with an AD‐like pattern of atrophy at older ages. CLINICAL TRIALS REGISTRATION NCT03821857 sex‐specific effects of endocrine disruption on aging and AD. Highlights Premenopausal bilateral oophorectomy (PBO) before the ages of 46 (early PBO) years and ages 46 to 49 (late PBO) years was studied. Early PBO was associated with reduced entorhinal cortex thickness later in life. Early PBO was associated with greater amyloid beta (Aβ) load at older ages. Early PBO was associated with greater Alzheimer's disease pattern of atrophy at older ages. Early PBO was associated with higher tau load at higher Aβ levels.

Abstract INTRODUCTION Early‐onset Alzheimer's disease (EOAD) and late‐onset Alzheimer's disease (LOAD) share similar amyloid etiology, but evidence from smaller‐scale studies suggests that they manifest differently clinically. Current analyses sought to contrast the cognitive profiles of EOAD and LOAD. METHODS Z‐ score cognitive‐domain composites for 311 amyloid‐positive sporadic EOAD and 314 amyloid‐positive LOAD participants were calculated from baseline data from age‐appropriate control cohorts. Z‐ score composites were compared between AD groups for each domain. RESULTS After controlling for cognitive status, EOAD displayed worse visuospatial, executive functioning, and processing speed/attention skills relative to LOAD, and LOAD displayed worse language, episodic immediate memory, and episodic delayed memory. DISCUSSION Sporadic EOAD possesses distinct cognitive profiles relative to LOAD. Clinicians should be alert for non‐amnestic impairments in younger patients to ensure proper identification and intervention using disease‐modifying treatments. Highlights Both early‐onset Alzheimer's disease (EOAD) and late‐onset Alzheimer's disease (LOAD) participants displayed widespread cognitive impairments relative to their same‐aged peers. Cognitive impairments were more severe for EOAD than for LOAD participants in visuospatial and executive domains. Memory and language impairments were more severe for LOAD than for EOAD participants Results were comparable after removing clinical phenotypes of posterior cortical atrophy (PCA), primary progressive aphasia (lv‐PPA), and frontal‐variant AD.

Introduction: The Mindfulness-Based Stress Reduction program for breast cancer survivors (MBSR [BCs]) is a stress-reducing program designed to increase cognitive functioning through four meditational practices. This randomized clinical trial aimed to determine if improvements in cognitive functioning and perceived cognitive abilities achieved from the MBSR(BC) were mediated through increased mindfulness, decreased rumination, and decreased perceived stress. Methods: Breast cancer survivors (BCSs) who met inclusion criteria of stage I, II, or III BC and received either chemotherapy (CT) or both CT and radiation were randomized to either the 6-week MBSR(BC), or Breast Cancer Education Support (BCES) program, or to a usual care (UC) regimen. Analysis of covariance was first implemented to identify potential mediators, followed by a formal mediational analysis to evaluate the effects of MBSR(BC) on 6-, 12-, and 26-week outcomes. Results: After consent, 212 BCS were randomized to MBSR(BC) ( n = 91), BCES ( n = 90), or UC ( n = 31). The mean age was 56.5 and the majority of the BCS, 73.1%, were White and non-Hispanic. Results showed increases in “observing” as part of mindfulness as a potential mediator of MBSR(BC) effects on impairments on quality of life and logical memory at 6 months relative to UC. No mediation effects were identified for outcomes measured at 6 or 12 weeks and also when MBSR(BC) was compared with the BCES program. Discussion: These results partially supported our hypothesis that improvement in cognitive functioning would occur through increased mindfulness. Although few mediating relationships were identified, results showed a relationship between mindfulness and cognitive functioning. Both mediating relationships occurred through increases in “observing,” a subconcept of “mindfulness,” when compared to the MBSR(BC) with UC at 6 months. This study shows that mediators may help “optimize” clinical therapeutic treatment effects, thus contributing to the advancement of science. Trial Registration: ClinicalTrials.gov, www.ClinicalTrials.gov . Registration Number: NCT02786797.

Giant cell arteritis (GCA) is a relapsing large vessel vasculitis with risk of serious ischemic manifestations, including vision loss and vascular damage in the form of large artery stenosis, aneurysms, and dissections. Approximately 50% of patients treated with glucocorticoid (GC) monotherapy and 30% of patients receiving adjunctive therapy with tocilizumab experience disease relapses, often during the first 2 years after diagnosis. Although most relapses in GCA do not involve life‐ or organ‐threatening presentations and can be controlled successfully, frequent relapses may lead to increased prescription of GC and consequent treatment‐related morbidity, in addition to risk of further vascular damage. Emerging data suggest that persistent disease activity may lead to increased vascular morbidity. Additionally, although tocilizumab decreases the frequency of relapses, more than 50% of patients relapse after discontinuation of therapy. Therefore, although interleukin‐6 blockade suppresses disease activity, it does not restore tolerance. In this article, we discuss the practical diagnosis and management of GCA relapses from an expert perspective. Current treatment options for GCA relapses, including those recommended by international guidelines, and novel potential therapies are reviewed.

Abstract The overall goal of the Alzheimer's Disease Neuroimaging Initiative (ADNI) is to optimize and validate biomarkers for clinical trials while sharing all data and biofluid samples with the global scientific community. ADNI has been instrumental in standardizing and validating amyloid beta (Aβ) and tau positron emission tomography (PET) imaging. ADNI data were used for the US Food and Drug Administration (FDA) approval of the Fujirebio and Roche Elecsys cerebrospinal fluid diagnostic tests. Additionally, ADNI provided data for the trials of the FDA‐approved treatments aducanumab, lecanemab, and donanemab. More than 6000 scientific papers have been published using ADNI data, reflecting ADNI's promotion of open science and data sharing. Despite its enormous success, ADNI has some limitations, particularly in generalizing its data and findings to the entire US/Canadian population. This introduction provides a historical overview of ADNI and highlights its significant accomplishments and future vision to pioneer “the clinical trial of the future” focusing on demographic inclusivity. Highlights The Alzheimer's Disease Neuroimaging Initiative (ADNI) introduced a novel model for public‐private partnerships and data sharing. It successfully validated amyloid and Tau PET imaging, as well as CSF and plasma biomarkers, for diagnosing Alzheimer's disease. ADNI generated and disseminated vital data for designing AD clinical trials.

BACKGROUND Rotational vertebral artery occlusion, or bow hunter’s syndrome (BHS), is a rare but clinically important cause of vertebrobasilar insufficiency. Extrinsic compression of the artery is usually caused by osteophytes, fibrous bands, or lateral disc herniation and typically occurs in the setting of anatomical variations, leading to dynamic compromise of the posterior circulation. Neoplastic causes of BHS are rare. OBSERVATIONS The authors present the case of a 72-year-old man with a left vertebral artery–dominant posterior circulation and isolated small right vertebral artery terminating in the posterior inferior cerebellar artery (PICA). He developed progressively worsening dynamic insufficiency of his right PICA circulation due to compression of the right vertebral artery at C2 from an intradural-extradural dumbbell-shaped lesion. This patient was successfully treated via surgical debulking of the lesion and cervical spine fixation and experienced no neurological deficits postoperatively. LESSONS This neoplastic change represents an exceedingly rare presentation for BHS, which warrants further study on its etiology and treatment. https://thejns.org/doi/10.3171/CASE24415