Antiamyloid Monoclonal Antibodies in Alzheimer's Disease Part 2: Challenges in Dementia Care Delivery System Logistics.

Alzheimer's disease (AD) is a common neurodegenerative illness affecting nearly 7 million people in the United States. Until 2023, no disease-targeting pharmacotherapeutics were widely available outside of research studies. With relatively recent regulatory approval and increasing availability of antiamyloid therapies (AATs) in the United States, management of AD is rapidly shifting from symptomatic and supportive care alone to treatments aimed at disease modification.

The Neurofibrillary Tangle Maturity Scale: A Novel Framework for Tangle Pathology Evaluation in Alzheimer's Disease.

Neurofibrillary tangles are dynamic neuropathologic hallmarks of Alzheimer's disease with a hypothesized lifespan morphologically-defined by three maturity levels: pretangles, mature tangles, and ghost tangles. To better understand the progression of tangle pathophysiology, we characterized tangle maturity level predilection of 15 tau antibodies recognizing a broad range of linear, phosphorylation, conformational, and truncation epitopes in the hippocampus of 24 postmortem brains. We developed the tangle maturity scoring system to semi-quantitatively evaluate each tangle maturity level.

Diagnostic performance of plasma p-tau217 and Aβ42/40 biomarkers in the outpatient memory clinic.

Introduction: Plasma biomarkers of Alzheimer's disease (AD) represent accessible alternatives to positron emission tomography (PET) and cerebrospinal fluid (CSF)-based biomarkers in well-characterized cohorts. It remains to be determined whether performance is maintained in outpatient clinics comprised of patients with multiple causes of cognitive impairment.

Methods: Plasma phosphorylated tau217 (p-tau217) and amyloid beta (Aβ) 42/40 were measured in 509 patients evaluated in a tertiary-care memory clinic.

Antiamyloid Monoclonal Antibodies in Alzheimer's Disease, Part 1: Patient Selection.

The availability of monoclonal antibodies directed against amyloid beta, for use as disease-modifying therapies for Alzheimer's disease (AD), represented a major shift in the field of AD research and treatment. U.S.

Alzheimer Disease Cerebrospinal Fluid Biomarkers in a Tertiary Neurology Practice.

Objective: To evaluate the performance of Alzheimer disease (AD) cerebrospinal fluid (CSF) biomarkers in a tertiary neurology clinic setting with high frequency of non-AD cases, including normal pressure hydrocephalus (NPH).

Methods: There were 534 patients who underwent AD CSF biomarkers (Roche Elecsys Aβ42, p-Tau181, total-Tau) from April 1, 2020, through April 23, 2021. A behavioral neurologist blinded to CSF results assigned a clinical diagnosis retrospectively on the basis of consensus criteria, and a neuroradiologist blinded to the diagnosis and CSF studies graded brain magnetic resonance images for indicators of CSF dynamics disorders.

Electroconvulsive therapy in N-methyl-d-aspartate receptor encephalitis: A retrospective cohort and scoping review of literature.

Neuropsychiatric symptoms in N-methyl-d-aspartate receptor encephalitis (NMDARE) have led some to pursue empiric trials of electroconvulsive therapy (ECT). A scoping review identified 39 patients diagnosed with NMDARE undergoing ECT. Separately, a retrospective cohort was reviewed to characterize 21 patients.

Clinicopathologic Heterogeneity and Glial Activation Patterns in Alzheimer Disease.

Importance: Factors associated with clinical heterogeneity in Alzheimer disease (AD) lay along a continuum hypothesized to associate with tangle distribution and are relevant for understanding glial activation considerations in therapeutic advancement.

Objectives: To examine clinicopathologic and neuroimaging characteristics of disease heterogeneity in AD along a quantitative continuum using the corticolimbic index (CLix) to account for individuality of spatially distributed tangles found at autopsy.

Design, Setting, And Participants: This cross-sectional study was a retrospective medical record review performed on the Florida Autopsied Multiethnic (FLAME) cohort accessioned from 1991 to 2020.

Best Practices for Communicating a Diagnosis of Dementia: Results of a Multi-Stakeholder Modified Delphi Consensus Process.

Background And Objectives: Many individuals with dementia and their families report not receiving a dementia diagnosis. Previously published standards for delivering a dementia diagnosis are now more than 10 years old and were developed without patient and caregiver input. The objective of this study was to identify best practices for delivering a diagnosis of dementia using existing literature, involvement of diverse stakeholders, and consensus building through a formal modified Delphi approach.

Disparate Dementia Risk Factors Are Associated with Cognitive Impairment and Rates of Decline in African Americans.

Objective: This study was undertaken to evaluate the frequency of modifiable dementia risk factors and their association with cognitive impairment and rate of decline in diverse participants engaged in studies of memory and aging.

Methods: Modifiable dementia risk factors and their associations with cognitive impairment and cognitive decline were determined in community-dwelling African American (AA; n = 261) and non-Hispanic White (nHW; n = 193) participants who completed ≥2 visits at the Mayo Clinic Alzheimer Disease Research Center in Jacksonville, Florida. Risk factors and their associations with cognitive impairment (global Clinical Dementia Rating [CDR] ≥ 0.

Association of Plasma Biomarkers of Alzheimer Disease With Cognition and Medical Comorbidities in a Biracial Cohort.

Background And Objectives: Recent advances in blood-based biomarkers offer the potential to revolutionize the diagnosis and management of Alzheimer disease (AD), but additional research in diverse populations is critical. We assessed the profiles of blood-based AD biomarkers and their relationships to cognition and common medical comorbidities in a biracial cohort.

Methods: Participants were evaluated through the Mayo Clinic Jacksonville Alzheimer Disease Research Center and matched on age, sex, and cognitive status.

Retrospective Evaluation of Neuropathologic Proxies of the Minimal Atrophy Subtype Compared With Corticolimbic Alzheimer Disease Subtypes.

Background And Objectives: Alzheimer disease (AD) is neuropathologically classified into 3 corticolimbic subtypes based on the neurofibrillary tangle distribution throughout the hippocampus and association cortices: limbic predominant, typical, and hippocampal sparing. In vivo, a fourth subtype, dubbed "minimal atrophy," was identified using structural MRI. The objective of this study was to identify a neuropathologic proxy for the neuroimaging-defined minimal atrophy subtype.

Age-Specific Barriers and Facilitators to Research Participation Amongst African Americans in Observational Studies of Memory and Aging.

Background: Black/African Americans experience a high burden of Alzheimer disease and related dementias yet are critically underrepresented in corresponding research. Understanding barriers and facilitators to research participation among younger and older African Americans is necessary to inform age-specific strategies to promote equity in studies of early- and late-onset neurodegenerative diseases.

Study Design: Survey respondents (n = 240) rated barriers and facilitators of research participation.

Cancer and Vascular Comorbidity Effects on Dementia Risk and Neuropathology in the Oldest-Old.

Background: Dementia, vascular disease, and cancer increase with age, enabling complex comorbid interactions. Understanding vascular and cancer contributions to dementia risk and neuropathology in oldest-old may improve risk modification and outcomes.

Objective: Investigate the contributions of vascular factors and cancer to dementia and neuropathology.

Phosphorylated tau sites that are elevated in Alzheimer's disease fluid biomarkers are visualized in early neurofibrillary tangle maturity levels in the post mortem brain.

Introduction: Alzheimer's disease (AD) biomarkers are increasingly more reliable in predicting neuropathology. To facilitate interpretation of phosphorylated tau sites as an early fluid biomarker, we sought to characterize which neurofibrillary tangle maturity levels (pretangle, intermediary 1, mature tangle, intermediary 2, and ghost tangle) are recognized.

Methods: We queried the Florida Autopsied Multi-Ethnic (FLAME) cohort for cases ranging from Braak stages I through VI, excluding non-AD neuropathologies and tauopathies.

Intensive care unit delirium in patients with severe COVID-19: A prospective observational cohort study.

Background: Delirium is common in patients with severe coronavirus disease-19 (COVID-19). The purpose of our study was to determine whether severe COVID-19 is an independent risk factor for the development of delirium in patients treated in the intensive care unit (ICU).

Methods: This prospective observational cohort study involved 162 critically ill patients admitted to a multidisciplinary ICU during 2019 and 2020.

Chemokines in ICU Delirium: An Exploratory Study.

Objectives: The pathophysiology of delirium is complex and incompletely understood. Inflammation is hypothesized to be integral to its development due to effects on blood brain barrier integrity, facilitation of leukocyte extravasation into brain parenchyma, and propagation of neuroinflammation. Septic shock is the prototypical condition associated with ICU delirium; however, the relative contribution of resultant hypotension and systemic inflammation to the development of delirium is unknown.

Cytokine profiles in intensive care unit delirium.

Background: Neuroinflammation causing disruption of the blood-brain barrier and immune cell extravasation into the brain parenchyma may cause delirium; however, knowledge of the exact pathophysiologic mechanism remains incomplete. The purpose of our study was to determine whether cytokine profiles differ depending on whether delirium occurs in the setting of sepsis, coronavirus disease 2019 (COVID-19), or recent surgery.

Methods: This prospective observational cohort study involved 119 critically ill patients admitted to a multidisciplinary intensive care unit (ICU) during 2019 and 2020.

The temporal onset of the core features in dementia with Lewy bodies.

Introduction: We examined the temporal sequence of the core features in probable dementia with Lewy bodies (DLB).

Methods: In 488 patients with probable DLB, the onset of each core feature and time to diagnosis was determined for men and women, and a pathologic subgroup (n = 209).

Results: REM sleep behavior disorder (RBD) developed before the other core features in men and women.

Older adults on involuntary hold status in the emergency department.

Background: As the United States' population ages, the health care system will experience overall change. This study aims to identify factors in the older adult that may contribute to involuntary hold status in the ED.

Methods: This study is a retrospective review conducted at a suburban acute-care hospital ED of adult patients evaluated while on involuntary hold from January 1, 2014, through November 30, 2015.

Are pre-existing psychiatric disorders the only reason for involuntary holds in the emergency department?

Objectives: To determine the role of previous psychiatric disorders including substance use disorders on emergency department (ED) patients on involuntary holds and compare presentations, treatment, and outcomes based on cause.

Methods: We conducted a retrospective study of patients ≥ 18 years old on involuntary holds in the ED of a tertiary care center from January 1, 2013, to November 30, 2015. Demographic and clinical information were collected.

Patients Threatening Harm to Others Evaluated in the Emergency Department under the Florida Involuntary Hold Act (Baker Act).

Objectives: This study describes the specific threats of harm to others that led to the use of the Baker Act, the Florida involuntary hold act for emergency department (ED) evaluations. The study also summarizes patient demographics, concomitant psychiatric diagnoses, and emergent medical problems.

Methods: This is a retrospective review of 251 patients evaluated while on involuntary hold from January 1, 2014 through November 30, 2015 at a suburban acute care hospital ED.

Involuntary patient length-of-stay at a suburban emergency department.

Background: Patients who may be a danger to themselves or others often are placed on involuntary hold status in the Emergency Department (ED). Our primary objective was to determine if there are demographic and/or clinical variables of involuntary hold patients which were associated with an increased ED LOS.

Methods: Records of ED patients evaluated while on involuntary hold from January 1, 2014 through November 30, 2015 at a suburban acute-care hospital ED were reviewed.

Patients on Involuntary Hold Status in the Emergency Department.

Objectives: Patients requiring involuntary holds are frequently seen in the emergency department (ED). Much of what is known comes from studies of patients at urban academic centers. Our aim was to describe the demographic and clinical characteristics of patients who were evaluated while on involuntary status at a suburban ED.

Frequency and predictors of the potential overprescribing of antidepressants in elderly residents of a geographically defined U.S. population.

The purpose of this study was to estimate the extent of potential antidepressant overprescribing in a geographically defined U.S. population, and to determine the indications and factors that account for it.