Statin Initiation and Risk of Incident Alzheimer Disease and Cognitive Decline in Genetically Susceptible Older Adults.

Background And Objectives: The association of statin initiation with incident Alzheimer disease (AD) dementia and cognitive decline by the ε4 allele is unknown. Our objective was to examine whether the association of statin initiation with incident AD dementia and cognitive decline differs by the ε4 allele.

Methods: This population-based longitudinal cohort study was conducted in 4 urban communities in Chicago, IL, United States, consisting of 4,807 participants.

Hyperthyroidism Due to Graves Disease After Radiofrequency Ablation.

Management options for benign, autonomously functioning, and malignant thyroid nodules were limited to surgery or targeting by radioactive iodine before the availability of radiofrequency ablation (RFA). Despite being a relatively new technique, RFA may be favored for patients of high surgical risk, and for those who wish to avoid hypothyroidism. Although insurance coverage for the procedure can be a significant barrier, several groups of investigators have shown improved quality of life for RFA compared to surgery, due to the less invasive nature and favorable risk profile.

Critical Approach to Hypothyroid Patients With Persistent Symptoms.

Hypothyroidism is a common condition, and numerous studies have been published over the last decade to assess the potential risks associated with this disorder when inappropriately treated. The standard of care for treatment of hypothyroidism remains levothyroxine (LT4) at doses to achieve biochemical and clinical euthyroidism. However, about 15% of hypothyroid patients experience residual hypothyroid symptoms.

Longitudinal Changes in Blood Biomarkers of Clinical Alzheimer Disease in a Biracial Population Sample.

Background And Objectives: Recent studies suggest the utility of blood biomarkers in detecting changes in neurodegenerative disorders. The objective of our research was to test the hypothesis that the longitudinal changes in total tau (t-tau), neurofilament light chain (Nf-L), and glial fibrillary acidic protein (GFAP) are associated with structural MRI and the development of clinical Alzheimer disease (AD) and cognitive decline.

Methods: Data came from a population-based sample with serum concentrations of t-tau, Nf-L, and GFAP and cognitive characteristics measured over 17 years.

Risk of Permanent Hypoparathyroidism Requiring Calcitriol Therapy in a Population-Based Cohort of Adults Older Than 65 Undergoing Total Thyroidectomy for Graves' Disease.

Total thyroidectomy for Graves' disease (GD) is associated with rapid treatment of hyperthyroidism and low recurrence rates. However, it carries the risk of surgical complications including permanent hypoparathyroidism, which contributes to long-term impaired quality of life. The objective of this study was to determine the incidence of permanent hypoparathyroidism requiring calcitriol therapy among a population-based cohort of older adults undergoing total thyroidectomy for GD in the United States.

Examination of Neurofilament Light Chain Serum Concentrations, Physical Activity, and Cognitive Decline in Older Adults.

Importance: Little is known about the association of serum neurofilament light chain (NfL) concentrations and physical activity with the rate of cognitive decline in older adults.

Objective: To examine the association of physical activity and NfL concentrations with cognitive decline in older adults over time.

Design, Setting, And Participants: This cohort study used data from the Chicago Health and Aging Project (CHAP), a population-based cohort study that recruited participants through door-to-door census in 4 Chicago-area communities and collected data between 1993 and 2012 in cycles of 3 years.

Brain Fog in Hypothyroidism: Understanding the Patient's Perspective.

Objective: Patient-centered studies have shown that several patients on thyroid hormone replacement therapy for hypothyroidism exhibit persistent symptoms, including "brain fog." Here, we aimed to determine which of these specific symptoms are associated with brain fog, identify patient-reported factors that modify these symptoms, and identify patient concerns related to brain fog not included in thyroid-specific questionnaires.

Methods: A survey on brain fog symptoms adapted from thyroid-specific patient-reported outcome was distributed online.

Longitudinal Association of Total Tau Concentrations and Physical Activity With Cognitive Decline in a Population Sample.

Importance: Tau is a brain protein located in neurons and develops abnormally in individuals with Alzheimer disease. New technology is convenient for measuring blood total tau concentrations and provides a unique and increased opportunity for early intervention to slow cognitive decline.

Objective: To evaluate the association of physical activity and total tau concentrations with cognitive decline at baseline and over time.

Comparative Effectiveness of Levothyroxine, Desiccated Thyroid Extract, and Levothyroxine+Liothyronine in Hypothyroidism.

Introduction: Studies comparing levothyroxine (LT4) therapy with LT4 + liothyronine (LT3) or desiccated thyroid extract (DTE) did not detect consistent superiority of either treatment. Here, we investigated these therapies, focusing on the whole group of LT4-treated hypothyroid patients, while also exploring the most symptomatic patients.

Methodology: Prospective, randomized, double-blind, crossover study of 75 hypothyroid patients randomly allocated to 1 of 3 treatment arms, LT4, LT4 + LT3, and DTE, for 22 weeks.

Population estimate of people with clinical Alzheimer's disease and mild cognitive impairment in the United States (2020-2060).

Introduction: The estimate of people with clinical Alzheimer's disease (AD) and mild cognitive impairment provides an understanding of the disease burden.

Methods: We estimated people with cognitive impairment using a quasibinomial regression model in 10,342 participants with cognitive test scores.

Results: The 2020 US Census-adjusted prevalence of clinical AD was 11.

Accelerating functional gene discovery in osteoarthritis.

Osteoarthritis causes debilitating pain and disability, resulting in a considerable socioeconomic burden, yet no drugs are available that prevent disease onset or progression. Here, we develop, validate and use rapid-throughput imaging techniques to identify abnormal joint phenotypes in randomly selected mutant mice generated by the International Knockout Mouse Consortium. We identify 14 genes with functional involvement in osteoarthritis pathogenesis, including the homeobox gene Pitx1, and functionally characterize 6 candidate human osteoarthritis genes in mouse models.

Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document.

Fourteen clinical trials have not shown a consistent benefit of combination therapy with levothyroxine (LT4) and liothyronine (LT3). Despite the publication of these trials, combination therapy is widely used and patients reporting benefit continue to generate patient and physician interest in this area. Recent scientific developments may provide insight into this inconsistency and guide future studies.

Temporal Pole Responds to Subtle Changes in Local Thyroid Hormone Signaling.

To study thyroid hormone (TH) signaling in the human brain, we analyzed published microarray data sets of the temporal pole (Brodmann area 38) of 19 deceased donors. An index of TH signaling built on the expression of 19 well known TH-responsive genes in mouse brains (T3S+) varied from 0.92 to 1.

Remote Blood Biomarkers of Longitudinal Cognitive Outcomes in a Population Study.

Objective: The longitudinal association of the blood biomarkers total tau (t-tau), neurofilament light (Nf-L), and glial fibrillary acidic protein (GFAP) with common sporadic Alzheimer disease (AD) and cognitive decline is not established.

Methods: Using a single molecule array technology, ultrasensitive immunoassays for serum concentrations of t-tau, Nf-L, and GFAP were measured in a population sample of 1,327 participants (60% African Americans and women) who had a clinical evaluation for AD, had completed in-home cognitive assessments, and had undergone 1.5T structural magnetic resonance imaging.

Temporal changes in the likelihood of dementia and MCI over 18 years in a population sample.

Objective: To examine the temporal changes in the likelihood of dementia and mild cognitive impairment (MCI) between 1993 and 2012 using a short battery of cognitive tests.

Methods: A cohort of 10,342 participants underwent a short battery of cognitive tests collected during triennial in-home interviews with 2,794 of those evaluated for the clinical diagnosis of dementia and MCI. We used a generalized logit regression model to estimate the likelihood of dementia and MCI, and a quasibinomial regression model to examine the temporal changes in those likelihood scores.

Race, APOEɛ4, and Long-Term Cognitive Trajectories in a Biracial Population Sample.

Background: The association of the APOEɛ4 allele with incident Alzheimer's dementia is higher among European Americans (EAs) than African Americans (AAs), but similar for the rate of cognitive decline.

Objective: To examine the racial differences in the association of the APOEɛ4 allele with incident Alzheimer's dementia and cognitive decline.

Methods: Using a population-based sample of 5,117 older adults (66% AAs and 63% females), we identified cognitive trajectory groups from a latent class mixed model and examined the association of the APOEɛ4 allele with these groups.

The Swinging Pendulum in Treatment for Hypothyroidism: From (and Toward?) Combination Therapy.

Thyroid hormone replacement for hypothyroidism can be achieved via several approaches utilizing different preparations of thyroid hormones, T3, and/or T4. "Combination therapy" involves administration of both T3 and T4, and was technically the first treatment for hypothyroidism. It was lauded as a cure for the morbidity and mortality associated with myxedema, the most severe presentation of overt hypothyroidism.

Disagreement Between Hospital Rating Systems: Measuring the Correlation of Multiple Benchmarks and Developing a Quality Composite Rank.

In the United States, hospital rating system usefulness is limited by heterogeneity and conflicting results. US News Best Hospitals, Vizient Quality and Accountability Study, Centers for Medicare & Medicaid Services (CMS) Star Rating, Leapfrog Hospital Safety Grade, and the Truven Top 100 Hospitals ratings were compared using Spearman correlations. Rank aggregation was used to combine the scores generating a Quality Composite Rank (QCR).

Apolipoprotein E Genotypes, Age, Race, and Cognitive Decline in a Population Sample.

Objectives: To examine the effects of age and race on the association of apolipoprotein E (APOE) genotypes with cognitive decline in a population sample.

Design: Longitudinal study of 18 years' duration.

Setting: Biracial urban US population sample.

Type 2 deiodinase polymorphism causes ER stress and hypothyroidism in the brain.

Levothyroxine (LT4) is a form of thyroid hormone used to treat hypothyroidism. In the brain, T4 is converted to the active form T3 by type 2 deiodinase (D2). Thus, it is intriguing that carriers of the Thr92Ala polymorphism in the D2 gene (DIO2) exhibit clinical improvement when liothyronine (LT3) is added to LT4 therapy.

Amiodarone and thyroid physiology, pathophysiology, diagnosis and management.

Although amiodarone is considered the most effective antiarrhythmic agent, its use is limited by a wide variety of potential toxicities. The purpose of this review is to provide a comprehensive "bench to bedside" overview of the ways amiodarone influences thyroid function. We performed a systematic search of MEDLINE to identify peer-reviewed clinical trials, randomized controlled trials, meta-analyses, and other clinically relevant studies.

Systemic Thyroid Hormone Status During Levothyroxine Therapy In Hypothyroidism: A Systematic Review and Meta-Analysis.

Context: The standard of care for overt hypothyroidism is levothyroxine at doses that normalize serum TSH levels. Whether this approach universally restores thyroid hormone signaling is unknown.

Objective: To review studies of overt hypothyroidism in which participants were treated with levothyroxine to normalize serum TSH levels and measured other objective markers of thyroid hormone signaling.