Impacts of informant replacement in two industry-sponsored Alzheimer's disease clinical trials.

Introduction: In Alzheimer's disease (AD) clinical trials, participants must enroll with a study partner informant who completes validated study instruments. We hypothesized that mid-trial informant replacement impacts study data in industry-sponsored trials.

Methods: We conducted a retrospective analysis of two industry-sponsored AD clinical trials testing semagacestat in mild-to-moderate AD dementia.

Association of plasma neurofilament light chain with microstructural white matter changes in Down syndrome.

Introduction: Both micro- and macrostructural white matter (WM) abnormalities, particularly those related to axonal degeneration, are associated with cognitive decline in adults with Down syndrome (DS) prior to a diagnosis of Alzheimer disease. Neurofilament light chain (NfL) is a support protein within myelinated axons released into blood following axonal damage. In this study we investigated cross-sectional relationships between WM microstructural changes as measured by diffusion tensor imaging (DTI) and plasma NfL concentration in adults with DS without dementia.

Effects of informant replacement in Alzheimer's disease clinical trials.

Introduction: Alzheimer's disease (AD) trials require enrollment with an informant.

Methods: We assessed relationships between informant replacement and Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) scores across four AD trials. Using generalized estimating equations, we examined associations between replacement and change in ADCS-ADL between successive visits.

Improving clinical efficiency in screening for cognitive impairment due to Alzheimer's.

Introduction: To reduce demands on expert time and improve clinical efficiency, we developed a framework to evaluate whether inexpensive, accessible data could accurately classify Alzheimer's disease (AD) clinical diagnosis and predict the likelihood of progression.

Methods: We stratified relevant data into three tiers: obtainable at primary care (low-cost), mostly available at specialty visits (medium-cost), and research-only (high-cost). We trained several machine learning models, including a hierarchical model, an ensemble model, and a clustering model, to distinguish between diagnoses of cognitively unimpaired, mild cognitive impairment, and dementia due to AD.

Pilot study of an Alzheimer's disease risk assessment program in a primary care setting.

Introduction: The goal of this study was to pilot a referral-based cognitive screening and genetic testing program for Alzheimer's disease (AD) risk assessment in a primary care setting.

Methods: Primary care providers (PCPs;  = 6) referred patients ( = 94; = 63 years) to the Rhode Island Alzheimer's Disease Prevention Registry for apolipoprotein E (APOE) genotyping and cognitive screening. PCPs disclosed test results to patients and counseled them about risk factor modification.

Alzheimer-related altered white matter microstructural integrity in Down syndrome: A model for sporadic AD?

Introduction: Virtually all adults with Down syndrome (DS) develop Alzheimer's disease (AD)-associated neuropathology by the age of 40, with risk for dementia increasing from the early 50s. White matter (WM) pathology has been reported in sporadic AD, including early demyelination, microglial activation, loss of oligodendrocytes and reactive astrocytes but has not been extensively studied in the at-risk DS population.

Methods: Fifty-six adults with DS (35 cognitively stable adults, 11 with mild cognitive impairment, 10 with dementia) underwent diffusion-weighted magnetic resonance imaging (MRI), amyloid imaging, and had assessments of cognition and functional abilities using tasks appropriate for persons with intellectual disability.

Racial and ethnic differences in older adults' willingness to be contacted about Alzheimer's disease research participation.

Introduction: We sought to examine the association of race/ethnicity with willingness to engage in studies that involve procedures typical of Alzheimer's disease (AD) clinical trials and determine whether any observed differences could be explained by research attitudes.

Methods: We studied 2749 adults aged ≥50 years who enrolled in a community-based recruitment registry.

Results: Compared to non-Hispanic (NH) whites (n = 2393, 87%), Hispanics (n = 191, 7%), NH Asians (n = 129, 5%) and NH blacks (n = 36, 1%) were 44%, 46%, and 64% less willing, respectively, to be contacted for studies that have requirements typical of AD prevention trials, namely: cognitive testing, brain imaging, blood draws, and investigational medications.

Repeated Exposure to Multiple Concurrent Stresses Induce Circuit Specific Loss of Inputs to the Posterior Parietal Cortex.

Severe loss of excitatory synapses in key brain regions is thought to be one of the major mechanisms underlying stress-induced cognitive impairment. To date, however, the identity of the affected circuits remains elusive. Here we examined the effect of exposure to repeated multiple concurrent stressors (RMS) on the connectivity of the posterior parietal cortex (PPC) in adolescent male mice.

The neuroscience of memory: implications for the courtroom.

Although memory can be hazy at times, it is often assumed that memories of violent or otherwise stressful events are so well encoded that they are effectively indelible and that confidently retrieved memories are almost certainly accurate. However, findings from basic psychological research and neuroscience studies indicate that memory is a reconstructive process that is susceptible to distortion. In the courtroom, even minor memory distortions can have severe consequences that are partly driven by common misunderstandings about memory--for example, that memory is more veridical than it may actually be.

A transgenic minipig model of Huntington's Disease.

Background: Some promising treatments for Huntington's disease (HD) may require pre-clinical testing in large animals. Minipig is a suitable species because of its large gyrencephalic brain and long lifespan.

Objective: To generate HD transgenic (TgHD) minipigs encoding huntingtin (HTT)1-548 under the control of human HTT promoter.

Sex difference and response to testosterone in gabaergic cells of the medial preoptic nucleus and ventral bed nuclei of the stria terminalis in gerbils.

The medial preoptic nucleus (MPN) and ventral bed nuclei of the stria terminalis (BST) are needed to maintain mating in sexually experienced male gerbils and rats. The gerbil ventral BST is also activated with mating, as assessed by Fos expression, as is the medial MPN (MPNm) of both species. In gerbils, many of those mating-activated cells contain glutamic acid decarboxylase (GAD), the enzyme that synthesizes γ-aminobutyric acid (GABA).

The ubiquitin-proteasome system in Alzheimer's disease.

Accumulation of proteins is a recurring event in many neurodegenerative diseases, including Alzheimer's disease (AD). Evidence has suggested that protein accumulation may result from a dysfunction in the ubiquitin proteasome system (UPS). Indeed, there is clear genetic and biochemical evidence of an involvement of the ubiquitin proteasome system in AD.

Modulation of the electrophysiological correlates of retrieval cue processing by the specificity of task demands.

Retrieval orientation refers to the differential processing of retrieval cues according to the type of information sought from memory (e.g., words vs.