Association and multimodal model of retinal and blood-based biomarkers for detection of preclinical Alzheimer's disease.

Background: The potential diagnostic value of plasma amyloidogenic beta residue 42/40 ratio (Aβ42/Aβ40 ratio), neurofilament light (NfL), tau phosphorylated at threonine-181 (p-tau181), and threonine-217 (p-tau217) has been extensively discussed in the literature. We have also previously described the association between retinal biomarkers and preclinical Alzheimer's disease (AD). The goal of this study was to evaluate the association, and a multimodal model of, retinal and plasma biomarkers for detection of preclinical AD.

Correlation between motor symptoms, cognitive function, and optical coherence tomography findings in Parkinson's disease.

Purpose: This study aimed to evaluate the total macular thickness as well as the thickness of the inner and outer retinal layers in patients with Parkinson's disease. It also aimed to verify the correlation of these parameters with motor symptoms and cognitive function.

Methods: A total of 46 eyes of 23 patients with Parkinson's disease and 40 eyes of 20 healthy controls were included in the study.

Modulation of circulating free testosterone fraction by testosterone, dihydrotestosterone, and estradiol during testosterone replacement therapy.

Background: Testosterone, estradiol, and dihydrotestosterone share common ligand binding sites on sex hormone binding globulin and albumin. It is unknown whether and how changes in testosterone, dihydrotestosterone, and estradiol concentrations during testosterone replacement therapy affect free testosterone fraction.

Objective: To determine the effect of changes in testosterone, dihydrotestosterone, and estradiol concentrations on free testosterone fraction during testosterone replacement therapy of men with hypogonadism.

Acromegaly Disease Control Maintained After Switching From Injected Somatostatin Receptor Ligands to Oral Paltusotine.

Context: Paltusotine is a nonpeptide selective somatostatin receptor 2 agonist in development as once-daily oral treatment for acromegaly.

Objective: To evaluate the efficacy and safety of paltusotine in the treatment of patients with acromegaly previously controlled with injected somatostatin receptor ligands (SRLs).

Methods: This phase 3, randomized, double-blind, placebo-controlled trial enrolled adults with acromegaly who had IGF-I ≤1.

Testosterone Treatment and Fractures in Men with Hypogonadism.

Background: Testosterone treatment in men with hypogonadism improves bone density and quality, but trials with a sufficiently large sample and a sufficiently long duration to determine the effect of testosterone on the incidence of fractures are needed.

Methods: In a subtrial of a double-blind, randomized, placebo-controlled trial that assessed the cardiovascular safety of testosterone treatment in middle-aged and older men with hypogonadism, we examined the risk of clinical fracture in a time-to-event analysis. Eligible men were 45 to 80 years of age with preexisting, or high risk of, cardiovascular disease; one or more symptoms of hypogonadism; and two morning testosterone concentrations of less than 300 ng per deciliter (10.

Retinal mid-peripheral capillary free zones are enlarged in cognitively unimpaired older adults at high risk for Alzheimer's disease.

Background: Compared to standard neuro-diagnostic techniques, retinal biomarkers provide a probable low-cost and non-invasive alternative for early Alzheimer's disease (AD) risk screening. We have previously quantified the periarteriole and perivenule capillary free zones (mid-peripheral CFZs) in cognitively unimpaired (CU) young and older adults as novel metrics of retinal tissue oxygenation. There is a breakdown of the inner retinal blood barrier, pericyte loss, and capillary non-perfusion or dropout in AD leading to potential enlargement of the mid-peripheral CFZs.

Symptomatic benefits of testosterone treatment in patient subgroups: a systematic review, individual participant data meta-analysis, and aggregate data meta-analysis.

Background: Testosterone replacement therapy is known to improve sexual function in men younger than 40 years with pathological hypogonadism. However, the extent to which testosterone alleviates sexual dysfunction in older men and men with obesity is unclear, despite the fact that testosterone is being increasingly prescribed to these patient populations. We aimed to evaluate whether subgroups of men with low testosterone derive any symptomatic benefit from testosterone treatment.

Long-term efficacy and safety of osilodrostat in patients with Cushing's disease: results from the LINC 4 study extension.

Objective: To evaluate the long-term efficacy and safety of osilodrostat in patients with Cushing's disease.

Methods: The multicenter, 48-week, Phase III LINC 4 clinical trial had an optional extension period that was initially intended to continue to week 96. Patients could continue in the extension until a managed-access program or alternative treatment became available locally, or until a protocol amendment was approved at their site that specified that patients should come for an end-of-treatment visit within 4 weeks or by week 96, whichever occurred first.

Testosterone Treatment of Men with Unequivocal Hypogonadism Following Treatment of Organ-Confined Prostate Cancer.

Objective: To determine if testosterone treatment of men with unequivocal hypogonadism and organ-confined prostate cancer is associated with recurrence of the cancer. The testosterone dependence of metastatic prostate cancer has made physicians reluctant to treat hypogonadal men with testosterone even after treatment of prostate cancer. Prior studies of testosterone treatment of men with treated prostate cancer have not documented that the men were unequivocally hypogonadal.

Automated, calibration-free quantification of cortical bone porosity and geometry in postmenopausal osteoporosis from ultrashort echo time MRI and deep learning.

Background: Assessment of cortical bone porosity and geometry by imaging in vivo can provide useful information about bone quality that is independent of bone mineral density (BMD). Ultrashort echo time (UTE) MRI techniques of measuring cortical bone porosity and geometry have been extensively validated in preclinical studies and have recently been shown to detect impaired bone quality in vivo in patients with osteoporosis. However, these techniques rely on laborious image segmentation, which is clinically impractical.

MRI Quantification of Cortical Bone Porosity, Mineralization, and Morphologic Structure in Postmenopausal Osteoporosis.

Background Preclinical studies have suggested that solid-state MRI markers of cortical bone porosity, morphologic structure, mineralization, and osteoid density are useful measures of bone health. Purpose To explore whether MRI markers of cortical bone porosity, morphologic structure, mineralization, and osteoid density are affected in postmenopausal osteoporosis (OP) and to examine associations between MRI markers and bone mineral density (BMD) in postmenopausal women. Materials and Methods In this single-center study, postmenopausal women were prospectively recruited from January 2019 to October 2020 into two groups: participants with OP who had not undergone treatment, defined as having any dual-energy x-ray absorptiometry (DXA) T-score of -2.

What We Have Learned from The Testosterone Trials.

As men age, their serum concentration of total testosterone decreases only slightly, but because the concentration of sex hormone binding globulin increases, the concentration of free testosterone decreases to a greater degree. The testosterone trials demonstrated that testosterone treatment of elderly men who have low serum testosterone levels increases their sexual function, hemoglobin, and bone mineral density to moderate degrees, and their walking, vitality, and mood slightly. Testosterone treatment increases coronary artery noncalcified plaque volume.

Symptoms of Late-Onset Hypogonadism in Men.

A small percentage of older men are hypogonadal for no apparent reason other than age, a condition called late-onset hypogonadism. This condition is accompanied by symptoms, especially sexual symptoms, most notably decreased libido. Testosterone treatment of men who have late-onset hypogonadism improves all aspects of sexual function and also mood, depressive symptoms, and self-reported walking ability.

Avoid or Embrace? Practice Effects in Alzheimer's Disease Prevention Trials.

Demonstrating a slowing in the rate of cognitive decline is a common outcome measure in clinical trials in Alzheimer's disease (AD). Selection of cognitive endpoints typically includes modeling candidate outcome measures in the many, richly phenotyped observational cohort studies available. An important part of choosing cognitive endpoints is a consideration of improvements in performance due to repeated cognitive testing (termed "practice effects").

Adverse cardiovascular events and mortality in men during testosterone treatment: an individual patient and aggregate data meta-analysis.

Background: Testosterone is the standard treatment for male hypogonadism, but there is uncertainty about its cardiovascular safety due to inconsistent findings. We aimed to provide the most extensive individual participant dataset (IPD) of testosterone trials available, to analyse subtypes of all cardiovascular events observed during treatment, and to investigate the effect of incorporating data from trials that did not provide IPD.

Methods: We did a systematic review and meta-analysis of randomised controlled trials including IPD.

Randomized Trial of Osilodrostat for the Treatment of Cushing Disease.

Context: Cushing disease, a chronic hypercortisolism disorder, is associated with considerable morbidity and mortality. Normalizing cortisol production is the primary treatment goal.

Objective: We aimed to evaluate the safety and efficacy of osilodrostat, a potent, orally available 11βhydroxylase inhibitor, compared with placebo in patients with Cushing disease.

Testosterone treatment of late-onset hypogonadism - benefits and risks.

As men age, their serum testosterone concentration falls, the total testosterone concentration barely but the free testosterone concentration more so. Testosterone treatment of older men who have low testosterone concentrations can ameliorate several consequences of this fall, including libido and sexual activity, distance walked, hemoglobin and volumetric bone mineral density and strength, but not vitality and cognitive function. The possibility that testosterone treatment of late-onset hypogonadism increases the risks of benign prostatic hyperplasia, prostate cancer or heart disease has been suggested but will not be determined until larger and longer trials are conducted.

The Benefits and Risks of Testosterone Treatment in Older Hypogonadal Men.

As men age, their serum testosterone concentrations decrease-the total testosterone very little but the free testosterone more. Testosterone treatment of older men whose serum testosterone concentrations are unequivocally low to bring their testosterone levels to normal for young men improves their sexual function, walking, mood, bone mineral density, and hemoglobin, but does not improve their sense of vitality or cognitive function. This treatment has also been suspected of increasing the risk of prostate cancer, benign prostatic hyperplasia, and heart disease, but these possible risks have neither been confirmed nor refuted.

A Neuropsychological Perspective on Defining Cognitive Impairment in the Clinical Study of Alzheimer's Disease: Towards a More Continuous Approach.

The global fight against Alzheimer's disease (AD) poses unique challenges for the field of neuropsychology. Along with the increased focus on early detection of AD pathophysiology, characterizing the earliest clinical stage of the disease has become a priority. We believe this is an important time for neuropsychology to consider how our approach to the characterization of cognitive impairment can be improved to detect subtle cognitive changes during early-stage AD.