Building clinically relevant outcomes across the Alzheimer's disease spectrum.

Demonstrating that treatments are clinically meaningful across the Alzheimer's disease (AD) continuum is critical for meeting our goals of accelerating a cure by 2025. While this topic has been a focus of several Alzheimer's Association Research Roundtable (AARR) meetings, there remains no consensus as to what constitutes a "clinically meaningful outcome" in the eyes of patients, clinicians, care partners, policymakers, payers, and regulatory bodies. Furthermore, the field has not come to agreement as to what constitutes a clinically meaningful treatment effect at each stage of disease severity.

P-tau/Aβ42 and Aβ42/40 ratios in CSF are equally predictive of amyloid PET status.

Introduction: Measurement of amyloid beta (Aβ40 and Aβ42) and tau (phosphorylated tau [p-tau] and total tau [t-tau]) in cerebrospinal fluid (CSF) can be utilized to differentiate clinical and preclinical Alzheimer's disease dementia (AD) from other neurodegenerative processes.

Methods: CSF biomarkers were measured in 150 participants from the Mayo Clinic Study of Aging and the Alzheimer's Disease Research Center. P-tau/Aβ42 (Roche Elecsys, Fujirebio LUMIPULSE) and Aβ42/40 (Fujirebio LUMIPULSE) ratios were compared to one another and to amyloid positron emission tomography (PET) classification.

Restless Legs Syndrome Shows Increased Silent Postmortem Cerebral Microvascular Disease With Gliosis.

Background Patients with restless legs syndrome (RLS) have increased silent microvascular disease by magnetic resonance imaging. However, there has been no previous autopsy confirmation of these magnetic resonance imaging findings. RLS is also frequently associated with inflammatory and immunologically mediated medical disorders.

Cardiac F-Dopamine PET Distinguishes PD with Orthostatic Hypotension from Parkinsonian MSA.

Background: Parkinson's disease with orthostatic hypotension (PD + OH) can be difficult to distinguish clinically from the parkinsonian form of multiple system atrophy (MSA-P). Previous studies examined cardiac sympathetic neuroimaging to differentiate PD from MSA but without focusing specifically on PD + OH versus MSA-P, which often is the relevant differential diagnostic issue.

Objective: To investigate the utility of cardiac sympathetic neuroimaging by F-dopamine positron emission tomographic (PET) scanning for separating PD + OH from MSA-P.

Sex differences in CSF biomarkers for neurodegeneration and blood-brain barrier integrity.

Introduction: As cerebrospinal fluid (CSF) neurofilament light protein (NfL) and the CSF/serum albumin ratio (Q) are used in the clinical routine, the impact of demographic factors on these biomarkers is important to understand.

Methods: Participants were derived from two Swedish samples: the population-based H70 Study (n = 308, age 70) and a clinical routine cohort (CSF NfL, n = 8995, Q, n = 39252, age 0 to 95). In the population-based study, Q and NfL were examined in relation to sex, cardiovascular risk factors, and cerebral white matter lesions (WMLs).

Quantitative REM Sleep without Atonia in Parkinson's Disease and Essential Tremor.

Background: Rapid eye movement (REM) sleep behavior disorder (RBD) occurs occasionally in essential tremor (ET), but polysomnographic REM sleep without atonia (RSWA) analyses have been sparse.

Objective: To characterize the amount and distribution of polysomnographic RSWA, the electrophysiologic substrate of RBD, in patients with Parkinson's disease (PD) and ET.

Methods: We analyzed quantitative RSWA in 73 patients: PD (23), ET (23), and age-sex-matched controls (27).

Temporal Trends, Predictors, and Outcomes of Acute Ischemic Stroke in Acute Myocardial Infarction in the United States.

Background There are limited contemporary data prevalence and outcomes of acute ischemic stroke (AIS) complicating acute myocardial infarction (AMI). Methods and Results Adult (>18 years) AMI admissions using the National Inpatient Sample database (2000-2017) were evaluated for in-hospital AIS. Outcomes of interest included in-hospital mortality, hospitalization costs, length of stay, discharge disposition, and use of tracheostomy and percutaneous endoscopic gastrostomy.

Association of Hypertension According to New American College of Cardiology/American Heart Association Blood Pressure Guidelines With Incident Dementia in the ARIC Study Cohort.

Background The impact of the new 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guideline on dementia risk at the population level has not been evaluated. Methods and Results We studied dementia-free participants in the ARIC (Atherosclerosis Risk in Communities) Study cohort in 1987 to 1989. Hypertension was defined by 2003 Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure and 2017 ACC/AHA guidelines using blood pressure measured at baseline.

GTPase Regulator Associated with Focal Adhesion Kinase 1 (GRAF1) Immunoglobulin-Associated Ataxia and Neuropathy.

Background: To date, 10 patients with GTPase Regulator Associated with Focal Adhesion Kinase 1/Rho GTPase Activating Protein 26-Immunoglobulin (GRAF1/ARHGAP26-IgG) associated neurological disorders have been described, most with ataxia.

Objective: To report the clinical, oncological, and radiological associations of GRAF1 autoantibodies.

Methods: We identified 17 patients whose serum and/or cerebrospinal fluid IgG was confirmed to target GRAF1/ARHGAP26-IgG by both tissue-based immunofluorescence and transfected cell-based assay.

: A distal myopathy with polyglucosan bodies.

Mutations in glycogenin-1 () cause an adult-onset polyglucosan body myopathy. We report here a patient presenting with late-onset distal myopathy. We wish to highlight this rare clinical phenotype of -related myopathy and the histological clues leading to its diagnosis.

High Mortality Rates Among Patients With Non-Traumatic Intracerebral Hemorrhage and Atrial Fibrillation on Antithrombotic Therapy Are Independent of the Presence of Cerebral Amyloid Angiopathy: Insights From a Population-Based Study.

Background Intracerebral hemorrhage (ICH) risk is higher in elderly patients with atrial fibrillation on antithrombotic therapy as well as those with cerebral amyloid angiopathy (CAA). We investigated if mortality among patients with atrial fibrillation on antithrombotic therapy presenting with non-traumatic ICH was influenced by underlying CAA. Methods and Results We used the Rochester Epidemiology Project to identify 6045 patients with atrial fibrillation aged >55 years on anticoagulation or antiplatelet therapy from 1995 to 2016.

Progressive dysexecutive syndrome due to Alzheimer's disease: a description of 55 cases and comparison to other phenotypes.

We report a group of patients presenting with a progressive dementia syndrome characterized by predominant dysfunction in core executive functions, relatively young age of onset and positive biomarkers for Alzheimer's pathophysiology. Atypical frontal, dysexecutive/behavioural variants and early-onset variants of Alzheimer's disease have been previously reported, but no diagnostic criteria exist for a progressive dysexecutive syndrome. In this retrospective review, we report on 55 participants diagnosed with a clinically defined progressive dysexecutive syndrome with F-fluorodeoxyglucose-positron emission tomography and Alzheimer's disease biomarkers available.

Contemporary Management of Acute Ischemic Stroke Across the Continuum: From TeleStroke to Intra-Arterial Management.

In this comprehensive contemporary review of acute ischemic stroke management, what is new and different will be highlighted beginning with prehospital stroke systems of care, emergency medical systems, and mobile stroke units, followed by hospital stroke teams, emergency evaluation, telemedicine, and brain and vascular imaging, and finishing with emergency treatments including thrombolysis and mechanical thrombectomy.

Treatment of Status Epilepticus: What Are the Guidelines and Are We Following Them?

Objectives: Status epilepticus (SE) is associated with high morbidity and mortality. The American Epilepsy Society (AES) has established guidelines regarding proper dosing of antiepileptic drugs (AEDs). There are also recommendations for appropriate weaning off anesthetic agents in SE.

Relationships between big-five personality factors and Alzheimer's disease pathology in autosomal dominant Alzheimer's disease.

Introduction: Changes in personality characteristics are associated with the onset of symptoms in Alzheimer's disease (AD) and may even precede clinical diagnosis. However, personality changes caused by disease progression can be difficult to separate from changes that occur with normal aging. The Dominantly Inherited Alzheimer Network (DIAN) provides a unique cohort in which to relate measures of personality traits to in vivo markers of disease in a much younger sample than in typical late onset AD.

Cerebral sinovenous thrombosis in pediatric hemolytic uremic syndrome.

Hemolytic uremic syndrome (HUS) may result in thrombotic central nervous system complications. We present a child with diarrhea-associated HUS who developed new-onset focal seizures secondary to cerebral sinovenous thrombosis (CSVT). Her CSVT was treated with low-molecular-weight heparin.

Brain-responsive neurostimulation treatment in patients with GAD65 antibody-associated autoimmune mesial temporal lobe epilepsy.

Glutamic acid decarboxylase 65-kilodalton isoform (GAD65) antibodies have been associated with multiple nonneurological and neurological syndromes including autoimmune epilepsy (AE). Although immunotherapy remains the cornerstone for the treatment of AE, those with GAD65 Ab-associated AE (GAD65-AE) remain refractory to immunotherapy and antiseizure medication (ASM). Outcomes of epilepsy surgery in this patient population have also been unsatisfactory.

Developmental brain abnormalities and acute encephalopathy in a patient with myopathy with extrapyramidal signs secondary to pathogenic variants in MICU1.

Mitochondria play a variety of roles in the cell, far beyond their widely recognized role in ATP generation. One such role is the regulation and sequestration of calcium, which is done with the help of the mitochondrial calcium uniporter (MCU) and its regulators, MICU1 and MICU2. Genetic variations in MICU1 and MICU2 have been reported to cause myopathy, developmental disability and neurological symptoms typical of mitochondrial disorders.

Transcatheter Aortic Valve Replacement Programs: Clinical Outcomes and Developments.

Transcatheter aortic valve replacement is a relatively recent revolutionary treatment that has now become a standard procedure for treating severe aortic stenosis. In this article, the authors review the clinical history of transcatheter aortic valve replacement, summarize the major clinical trials, and describe the evolution of the technique over time. In doing so, the authors hope to provide a clear and concise review of the history and clinical evidence behind transcatheter aortic valve replacement.

Systematic Review of the Genetics of Sudden Unexpected Death in Epilepsy: Potential Overlap With Sudden Cardiac Death and Arrhythmia-Related Genes.

Background Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related death. SUDEP shares many features with sudden cardiac death and sudden unexplained death in the young and may have a similar genetic contribution. We aim to systematically review the literature on the genetics of SUDEP.