Intracerebroventricular administration of a modified hexosaminidase ameliorates late-stage neurodegeneration in a GM2 mouse model.

The GM2 gangliosidoses, Tay-Sachs disease and Sandhoff disease, are devastating neurodegenerative disorders caused by β-hexosaminidase A (HexA) deficiency. In the Sandhoff disease mouse model, rescue potential was severely reduced when HexA was introduced after disease onset. Here, we assess the effect of recombinant HexA and HexD3, a newly engineered mimetic of HexA optimized for the treatment of Tay-Sachs disease and Sandhoff disease.

A scoping review of dementia education programs to assess for the inclusion of culture.

This scoping review examined literature on dementia education programs (DEPs) for healthcare providers and students. The search was conducted using the Discover! search engine that includes 63 databases. The review included a total of 25 articles that met the eligibility criteria.

Mayo Normative Studies: regression-based normative data for remote self-administration of the Stricker Learning Span, Symbols Test and Mayo Test Drive Screening Battery Composite and validation in individuals with Mild Cognitive Impairment and dementia.

Objective: Few normative data for unsupervised, remotely-administered computerized cognitive measures are available. We examined variables to include in normative models for Mayo Test Drive (a multi-device remote cognitive assessment platform) measures, developed normative data, and validated the norms.

Method: 1240 Cognitively Unimpaired (CU) adults ages 32-100-years (96% white) from the Mayo Clinic Study of Aging and Mayo Alzheimer's Disease Research Center with Clinical Dementia Rating of 0 were included.

Continuous Associations between Remote Self-Administered Cognitive Measures and Imaging Biomarkers of Alzheimer's Disease.

Background: Easily accessible and self-administered cognitive assessments that can aid early detection for Alzheimer's disease (AD) dementia risk are critical for timely intervention.

Objectives/design: This cross-sectional study investigated continuous associations between Mayo Test Drive (MTD) - a remote, self-administered, multi-device compatible, web-based cognitive assessment - and AD-related imaging biomarkers.

Participants/setting: 684 adults from the Mayo Clinic Study of Aging and Mayo Clinic Alzheimer's Disease Research Center participated (age=70.

A validation study demonstrating portable motion capture cameras accurately characterize gait metrics when compared to a pressure-sensitive walkway.

Digital quantification of gait can be used to measure aging- and disease-related decline in mobility. Gait performance also predicts prognosis, disease progression, and response to therapies. Most gait analysis systems require large amounts of space, resources, and expertise to implement and are not widely accessible.

Mayo Normative Studies: Amyloid and Neurodegeneration Negative Normative Data for the Auditory Verbal Learning Test and Sex-Specific Sensitivity to Mild Cognitive Impairment/Dementia.

Background: Conventional normative samples include individuals with undetected Alzheimer's disease neuropathology, lowering test sensitivity for cognitive impairment.

Objective: We developed Mayo Normative Studies (MNS) norms limited to individuals without elevated amyloid or neurodegeneration (A-N-) for Rey's Auditory Verbal Learning Test (AVLT). We compared these MNS A-N- norms in female, male, and total samples to conventional MNS norms with varying levels of demographic adjustments.

Primary central nervous system vasculitis with intracranial aneurysm.

Background: Unruptured intracranial aneurysms (UIAs) are rarely reported in primary central nervous system vasculitis (PCNSV). In this study we described the clinical findings, response to therapy, and outcomes of UIA in a large cohort of PCNSV patients.

Methods: We retrospectively studied 216 consecutive patients with PCNSV, selected by predetermined diagnostic criteria, who were seen during a 40-year period.

Structural violence and necropolitics among Indigenous Peoples living with HIV who use substances in the Prairie provinces during COVID-19.

Background: Within Manitoba and Saskatchewan, pre-existing health inequities amongst Indigenous groups were intensified during the COVID-19 pandemic. Service disruptions in the health and social service sector-combined with the effects of intersectional stigma-disproportionately impacted Indigenous peoples living with HIV (IPLH). IPLH experience structural violence and necropolitical exclusion through systemic forms of stigma situated within Canada's expansive colonial history.

Low Dose Aspirin Initiation 18 Hours After Thrombolytic Therapy in Acute Ischemic Stroke.

Objectives: To investigate the safety of administering low-dose aspirin (81 mg) 18 hours after intravenous thrombolytic therapy.

Methods: This is a retrospective cohort investigation. Individuals received either alteplase or tenecteplase for acute ischemic stroke followed by aspirin 81 mg (after follow-up imaging).

The Gigii-Bapiimin Study: resilience and the impacts of COVID-19 on health and wellbeing of Indigenous people living with HIV in Manitoba and Saskatchewan.

The Gigii-Bapiimin study explored the impacts of the COVID-19 pandemic on the health and wellbeing of First Nations, Inuit, and Métis people living with HIV in Manitoba and Saskatchewan, two provinces in Canada with alarmingly high rates of HIV infections. Participants ( = 28 in Manitoba and  = 23 in Saskatchewan) were recruited using various methods, including flyers, community organizations, peers, and social media. The qualitative interviews focused on the pandemic's impact on health, access to services, and ceremonies.

Mayo normative studies: regression-based normative data for ages 30-91 years with a focus on the Boston Naming Test, Trail Making Test and Category Fluency.

Objective: Normative neuropsychological data are essential for interpretation of test performance in the context of demographic factors. The Mayo Normative Studies (MNS) aim to provide updated normative data for neuropsychological measures administered in the Mayo Clinic Study of Aging (MCSA), a population-based study of aging that randomly samples residents of Olmsted County, Minnesota, from age- and sex-stratified groups. We examined demographic effects on neuropsychological measures and validated the regression-based norms in comparison to existing normative data developed in a similar sample.

Activated Prothrombin Complex Concentrates for the Treatment of Factor Xa Inhibitor-Associated Spontaneous Intracerebral Hemorrhage.

Anticoagulant-associated intracerebral hemorrhage (ICH) is a significant cause of morbidity and mortality. Despite approval of a specific reversal agent for factor Xa inhibitors, there is still much interest in nonspecific reversal agents, such as activated prothrombin complex concentrates (aPCCs). The objective of this study was to describe ICH expansion in a cohort of patients with factor Xa inhibitor-associated ICH who were treated with aPCC.

Stricker Learning Span criterion validity: a remote self-administered multi-device compatible digital word list memory measure shows similar ability to differentiate amyloid and tau PET-defined biomarker groups as in-person Auditory Verbal Learning Test.

Objective: The Stricker Learning Span (SLS) is a computer-adaptive digital word list memory test specifically designed for remote assessment and self-administration on a web-based multi-device platform (Mayo Test Drive). We aimed to establish criterion validity of the SLS by comparing its ability to differentiate biomarker-defined groups to the person-administered Rey's Auditory Verbal Learning Test (AVLT).

Method: Participants ( = 353; mean age = 71, SD = 11; 93% cognitively unimpaired [CU]) completed the AVLT during an in-person visit, the SLS remotely (within 3 months) and had brain amyloid and tau PET scans available (within 3 years).

Intracerebroventricular dosing of N-sulfoglucosamine sulfohydrolase in mucopolysaccharidosis IIIA mice reduces markers of brain lysosomal dysfunction.

Mucopolysaccharidosis type IIIA (MPS IIIA) is a lysosomal storage disorder caused by N-sulfoglucosamine sulfohydrolase (SGSH) deficiency. SGSH removes the sulfate from N-sulfoglucosamine residues on the nonreducing end of heparan sulfate (HS-NRE) within lysosomes. Enzyme deficiency results in accumulation of partially degraded HS within lysosomes throughout the body, leading to a progressive severe neurological disease.

Mayo normative studies: A conditional normative model for longitudinal change on the Auditory Verbal Learning Test and preliminary validation in preclinical Alzheimer's disease.

Introduction: The aim of this study was to develop a conditional normative model for Rey's Auditory Verbal Learning Test (AVLT) that accounts for practice effects.

Methods: In our normative sample, robust conditional norms were derived from 1001 cognitively unimpaired (CU) adults ages 50 to 89 who completed the AVLT up to eight times. Linear mixed-effects models adjusted for baseline performance, prior test exposures, time, demographics, and interaction terms.

Initial antihypertensive agent effects on acute blood pressure after intracerebral haemorrhage.

Introduction: Current guidelines recommend blood pressure (BP) lowering in patients after acute intracerebral haemorrhage (ICH) without guidance on initial choice of antihypertensive class. This study sought to determine if initial antihypertensive class differentially effects acute BP lowering in a large multiethnic ICH cohort.

Methods: Subjects enrolled in the Ethnic/Racial Variations in ICH study between August 2010 and August 2017 with elevated admission BP and who received labetalol, nicardipine or hydralazine monotherapy as initial antihypertensive were analysed.

A longitudinal investigation of Aβ, anxiety, depression, and mild cognitive impairment.

Introduction: We investigated the longitudinal relationship between cortical amyloid deposition, anxiety, and depression and the risk of incident mild cognitive impairment (MCI).

Methods: We followed 1440 community-dwelling, cognitively unimpaired individuals aged ≥ 50 years for a median of 5.5 years.

Understanding Nursing Knowledge of Continence Care and Bladder Scanner Use in Long-Term Care: An Evaluation Study.

Because urinary continence is an essential indicator for quality of life for older adults in long-term care, it is important to accurately assess and treat those at risk for incontinence. This evaluation study was to increase understanding of the issues related to the implementation of bladder scanners while exploring nursing staff knowledge about continence care of older adults in long-term care settings. Using a mixed-methods design, nursing care staff (RN, LPN, Care Aide) at six long-term care homes completed a bladder care knowledge survey and participated in focus group discussions to explore continence care knowledge and use of bladder scanners to manage continence issues.

Neuropsychiatric symptoms and the outcome of cognitive trajectories in older adults free of dementia: The Mayo Clinic Study of Aging.

Objective: Neuropsychiatric symptoms (NPS) are associated with the risk of incident mild cognitive impairment (MCI) and dementia. We examined associations between NPS and the outcomes of global and domain-specific cognitive trajectories.

Methods: In this longitudinal study conducted in the setting of the population-based Mayo Clinic Study of Aging, 5081 community-dwelling, nondemented individuals aged ≥50 years (51% males) underwent NPS assessment using Neuropsychiatric Inventory Questionnaire (NPI-Q), and Beck Depression and Anxiety Inventories (BDI-II, BAI).

Association Between Neuropsychiatric Symptoms and Functional Change in Older Non-Demented Adults: Mayo Clinic Study of Aging.

We examined the associations between baseline neuropsychiatric symptoms (NPS) and longitudinal changes in functional performance among 5,394 non-demented individuals aged ≥50 years (2,729 males; median age 74.2 years; 4,716 cognitively unimpaired, 678 mild cognitive impairment). After adjusting for age, sex, education, and medical comorbidities, NPS assessed by the Neuropsychiatric Inventory Questionnaire, clinical depression (Beck Depression Inventory score ≥13) and anxiety (Beck Anxiety Inventory score ≥10) were significantly associated with an increase in the Functional Activities Questionnaire score, indicating functional decline over time.

Activity of transgene-produced B-domain-deleted factor VIII in human plasma following AAV5 gene therapy.

Adeno-associated virus (AAV)-based gene therapies can restore endogenous factor VIII (FVIII) expression in hemophilia A (HA). AAV vectors typically use a B-domain-deleted FVIII transgene, such as human FVIII-SQ in valoctocogene roxaparvovec (AAV5-FVIII-SQ). Surprisingly, the activity of transgene-produced FVIII-SQ was between 1.

Mayo Normative Studies: Regression-Based Normative Data for the Auditory Verbal Learning Test for Ages 30-91 Years and the Importance of Adjusting for Sex.

Objective: Rey's Auditory Verbal Learning Test (AVLT) is a widely used word list memory test. We update normative data to include adjustment for verbal memory performance differences between men and women and illustrate the effect of this sex adjustment and the importance of excluding participants with mild cognitive impairment (MCI) from normative samples.

Method: This study advances the Mayo's Older Americans Normative Studies (MOANS) by using a new population-based sample through the Mayo Clinic Study of Aging, which randomly samples residents of Olmsted County, Minnesota, from age- and sex-stratified groups.

Intermittent enzyme replacement therapy with recombinant human β-galactosidase prevents neuraminidase 1 deficiency.

Mutations in the β () gene cause lysosomal β-galactosidase (β-Gal) deficiency and clinical onset of the neurodegenerative lysosomal storage disease, GM1 gangliosidosis. β-Gal and neuraminidase 1 (NEU1) form a multienzyme complex in lysosomes along with the molecular chaperone, protective protein cathepsin A (PPCA). NEU1 is deficient in the neurodegenerative lysosomal storage disease sialidosis, and its targeting to and stability in lysosomes strictly depend on PPCA.

Brain Regional Glucose Metabolism, Neuropsychiatric Symptoms, and the Risk of Incident Mild Cognitive Impairment: The Mayo Clinic Study of Aging.

Objective: The authors conducted a prospective cohort study to examine the risk of incident mild cognitive impairment (MCI) as predicted by baseline neuropsychiatric symptoms (NPS) and brain regional glucose metabolic dysfunction.

Methods: About 1,363 cognitively unimpaired individuals (52.8% males) aged ≥50 years were followed for a median of 4.