Patient and Care Partner Perspective on Potential Undertreatment of Patients With Mild Cognitive Impairment for Cardiovascular Disease.

Background And Objectives: Mild cognitive impairment (MCI) affects up to 22% of US older adults aged 65 and older. Research suggests that physicians may recommend less cardiovascular disease (CVD) treatment for older adults with MCI due to assumptions about their preferences. To delve into the disparity between patient preferences and physician assumptions in CVD treatment recommendations, we conducted a multi-site qualitative study to explore the underlying reasons for this discrepancy, providing insights into potential communication barriers and strategies to enhance patient-physician relationships.

Cognitive and Cerebrospinal Fluid Alzheimer's Disease-related Biomarker Trajectories in Older Surgical Patients and Matched Nonsurgical Controls.

Background: Anesthesia and/or surgery accelerate Alzheimer's disease pathology and cause memory deficits in animal models, yet there is a lack of prospective data comparing cerebrospinal fluid (CSF) Alzheimer's disease-related biomarker and cognitive trajectories in older adults who underwent surgery versus those who have not. Thus, the objective here was to better understand whether anesthesia and/or surgery contribute to cognitive decline or an acceleration of Alzheimer's disease-related pathology in older adults.

Methods: The authors enrolled 140 patients 60 yr or older undergoing major nonneurologic surgery and 51 nonsurgical controls via strata-based matching on age, sex, and years of education.

Scheltens ratings, clinical white matter hyperintensities and executive functioning in the Cache County Memory Study.

Objective: Examine the association between neuropsychologically assessed executive function and clinically identifiable white matter burden from magnetic resonance imaging, using a visual rating system (Scheltens Rating System) applied to the Cache County Memory Study (CCMS) archival database.

Method: We used the Scheltens Ratings Scale to quantify white matter lesion burden in the CCMS sample and used this metric as a predictor of executive function. The sample included 60 individuals with dementia and 13 healthy controls.

Decision making in clinical trials: Interim analyses, innovative design, and biomarkers.

The efficient and accurate execution of clinical trials testing novel treatments for Alzheimer's disease (AD) is a critical component of the field's collective efforts to develop effective disease-modifying treatments for AD. The lengthy and heterogeneous nature of clinical progression in AD contributes to the challenges inherent in demonstrating a clinically meaningful benefit of any potential new AD therapy. The failure of many large and expensive clinical trials to date has prompted a focus on optimizing all aspects of decision making, to not only expedite the development of new treatments, but also maximize the value of the information that each clinical trial yields, so that all future clinical trials (including those that are negative) will contribute toward advancing the field.

TOMM40 '523 Genotype Distinguishes Patterns of Cognitive Improvement for Executive Function in APOEɛ3 Homozygotes.

Background: TOMM40 '523 has been associated with cognitive performance and risk for developing Alzheimer's disease independent of the effect of APOE genotype. Few studies have considered the longitudinal effect of this genotype on change in cognition over time.

Objective: Our objective was to evaluate the relationship between TOMM40 genotype status and change in cognitive performance in the TOMMORROW study, which was designed to prospectively evaluate an algorithm that includes TOMM40 '523 for genetic risk for conversion to mild cognitive impairment.

Meta-Analysis of Variations in Association between APOE ɛ4 and Alzheimer's Disease and Related Dementias Across Hispanic Regions of Origin.

Background: Emerging research has shown racial and ethnic variations in the magnitude of association between the apolipoprotein ɛ4 (APOE ɛ4) allele and the risk of developing Alzheimer's disease and related dementias (ADRD). Studies researching this association among Hispanic groups within and outside of the United States have produced inconsistent results.

Objective: To examine the association between the APOE ɛ4 allele and the risk of developing ADRD in global Hispanic populations from different ethnic regions of origin.

Influence of mild cognitive impairment on patient and care partner decision-making for acute ischemic stroke.

Goals: Evidence suggests that patients with mild cognitive impairment (MCI) receive fewer treatments for acute ischemic stroke and other cardiovascular diseases than patients with normal cognition. Little is known about how patient and care partner preferences for ischemic stroke treatment differ between the patient population with MCI and the population with normal cognition. This study aimed to understand how patient MCI diagnosis influences patient and care partner decision-making for acute ischemic stroke treatments.

Feasibility of a standard cognitive assessment in European academic memory clinics.

Introduction: Standardized cognitive assessment would enhance diagnostic reliability across memory clinics. An expert consensus adapted the Uniform Dataset (UDS)-3 for European centers, the clinician's UDS (cUDS). This study assessed its implementation acceptability and feasibility.

Remote self-administration of digital cognitive tests using the Brief Assessment of Cognition: Feasibility, reliability, and sensitivity to subjective cognitive decline.

Cognitive impairment is a common and pervasive feature of etiologically diverse disorders of the central nervous system, and a target indication for a growing number of symptomatic and disease modifying drugs. Remotely acquired digital endpoints have been recognized for their potential in providing frequent, real-time monitoring of cognition, but their ultimate value will be determined by the reliability and sensitivity of measurement in the populations of interest. To this end, we describe initial validation of remote self-administration of cognitive tests within a regulatorily compliant tablet-based platform.

A Mixed-Methods Study of the Impact of Mild Cognitive Impairment Diagnosis on Patient and Care Partner Perception of Health Risks.

Background: Older patients (≥65 years) with mild cognitive impairment (MCI) are undertreated for cardiovascular disease (CVD). One reason for this disparity could be that patients with MCI might underestimate the chances of CVD and overestimate dementia.

Objective: To compare conceptions of health risk between older patients with MCI and normal cognition (NC) and their care partners.

Acoustofluidic multimodal diagnostic system for Alzheimer's disease.

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative brain disorder that affects tens of millions of older adults worldwide and has significant economic and societal impacts. Despite its prevalence and severity, early diagnosis of AD remains a considerable challenge. Here we report an integrated acoustofluidics-based diagnostic system (ADx), which combines triple functions of acoustics, microfluidics, and orthogonal biosensors for clinically accurate, sensitive, and rapid detection of AD biomarkers from human plasma.

Recruitment of a multi-site randomized controlled trial of aerobic exercise for older adults with amnestic mild cognitive impairment: The EXERT trial.

Introduction: Effective strategies to recruit older adults with mild cognitive impairment (MCI) into nonpharmacological intervention trials are lacking.

Methods: Recruitment for EXERT, a multisite randomized controlled 18-month trial examining the effects of aerobic exercise on cognitive trajectory in adults with amnestic MCI, involved a diverse portfolio of strategies to enroll 296 participants.

Results: Recruitment occurred September 2016 through March 2020 and was initially slow.

Assessment of Neuropsychological Function in Veterans With Blast-Related Mild Traumatic Brain Injury and Subconcussive Blast Exposure.

The majority of combat-related head injuries are associated with blast exposure. While Veterans with mild traumatic brain injury (mTBI) report cognitive complaints and exhibit poorer neuropsychological performance, there is little evidence examining the effects of subconcussive blast exposure, which does not meet clinical symptom criteria for mTBI during the acute period following exposure. We compared chronic effects of combat-related blast mTBI and combat-related subconcussive blast exposure on neuropsychological performance in Veterans.

Safety and efficacy of pioglitazone for the delay of cognitive impairment in people at risk of Alzheimer's disease (TOMMORROW): a prognostic biomarker study and a phase 3, randomised, double-blind, placebo-controlled trial.

Background: The identification of people at risk of cognitive impairment is essential for improving recruitment in secondary prevention trials of Alzheimer's disease. We aimed to test and qualify a biomarker risk assignment algorithm (BRAA) to identify participants at risk of developing mild cognitive impairment due to Alzheimer's disease within 5 years, and to evaluate the safety and efficacy of low-dose pioglitazone to delay onset of mild cognitive impairment in these at-risk participants.

Methods: In this phase 3, multicentre, randomised, double-blind, placebo-controlled, parallel-group study, we enrolled cognitively healthy, community living participants aged 65-83 years from 57 academic affiliated and private research clinics in Australia, Germany, Switzerland, the UK, and the USA.

The Association Between Mild Cognitive Impairment Diagnosis and Patient Treatment Preferences: a Survey of Older Adults.

Background: Older patients (65+) with mild cognitive impairment (MCI) receive less guideline-concordant care for cardiovascular disease (CVD) and other conditions than patients with normal cognition (NC). One potential explanation is that patients with MCI want less treatment than patients with NC; however, the treatment preferences of patients with MCI have not been studied.

Objective: To determine whether patients with MCI have different treatment preferences than patients with NC.

Differentiating among stages of cognitive impairment in aging: Version 3 of the Uniform Data Set (UDS) neuropsychological test battery and MoCA index scores.

Introduction: Federally funded Alzheimer's Disease Centers in the United States have been using a standardized neuropsychological test battery as part of the National Alzheimer's Coordinating Center Uniform Data Set (UDS) since 2005. Version 3 (V3) of the UDS replaced the previous version (V2) in 2015. We compared V2 and V3 neuropsychological tests with respect to their ability to distinguish among the Clinical Dementia Rating (CDR) global scores of 0, 0.

Racially diverse participant registries to facilitate the recruitment of African Americans into presymptomatic Alzheimer's disease studies.

Introduction: The Alzheimer's Disease Prevention Registry (ADPR) of the Joseph and Kathleen Bryan Alzheimer's Disease Research Center at Duke University has been successful in achieving a racially diverse and "research ready" cohort of cognitively healthy volunteers.

Methods: The ADPR is based on an infrastructure that includes: (1) an administrative leadership team; (2) a coordinating center; (3) an IT management team; (4) a community engagement team; and (5) collaborations with study partners across disciplines.

Results: The ADPR currently has more than 4677 members, 26% of whom are African American.

Longer Term Effects of Diet and Exercise on Neurocognition: 1-Year Follow-up of the ENLIGHTEN Trial.

Objectives: To evaluate the longer term changes in executive functioning among participants with cardiovascular disease (CVD) risk factors and cognitive impairments with no dementia (CIND) randomized to a diet and exercise intervention.

Design: A 2 (Exercise) × 2 (Dietary Approaches to Stop Hypertension [DASH] eating plan) factorial randomized clinical trial.

Setting: Academic tertiary care medical center.

The TOMMORROW study: Design of an Alzheimer's disease delay-of-onset clinical trial.

Introduction: Alzheimer's disease (AD) is a continuum with neuropathologies manifesting years before clinical symptoms; thus, AD research is attempting to identify more disease-modifying approaches to test treatments administered before full disease expression. Designing such trials in cognitively normal elderly individuals poses unique challenges.

Methods: The TOMMORROW study was a phase 3 double-blind, parallel-group study designed to support qualification of a novel genetic biomarker risk assignment algorithm (BRAA) and to assess efficacy and safety of low-dose pioglitazone to delay onset of mild cognitive impairment due to AD.