A Decade of Protecting Progress: Ethics Review.

Ethics Review began a decade ago with a mission to identify ethical concerns that hold back innovation and to promote solutions that would move the field forward. Over this time, blood biomarkers for brain pathology and medications that treat that pathology promise to transform research and care. A central problem is that the evidence needed to guide test interpretation and practice is accumulating and there are unanswered questions.

Biomarker disclosure protocols in prodromal Alzheimer's disease clinical trials.

Introduction: The development of biomarkers for Alzheimer's disease (AD) has allowed researchers to increase sample homogeneity and test candidate treatments earlier in the disease. The integration of biomarker "screening" criteria should be met with a parallel implementation of standardized methods to disclose biomarker testing results to research participants; however, the extent to which protocolized disclosure occurs in trials is unknown.

Methods: We reviewed the literature to identify prodromal AD trials published in the past 10 years.

The Ethics of Using Caregivers as Cognitive Testers.

O'Caoimh et al. demonstrated that caregivers or family members could administer and score a brief cognitive screening instrument and detect cognitive impairment with comparable accuracy to similar measures administered in-person by trained staff. This novel approach challenges us to consider the boundaries of how caregivers or other family members are used in remote testing.

Disclosing Individual Results in Dementia Research: A Proposed Study Participant's Bill of Rights.

This Study Participant's Bill of Rights is a call to action for researchers in Alzheimer's disease and related dementias (ADRD) to proactively design clinical studies that provide the option for research participants to learn their individual research results if they choose, and in a manner that ensures study integrity. This Bill of Rights was crafted by a committee of study participants, care partners, representatives of dementia advocacy organizations, and other stakeholders in dementia research for the Advisory Group on Risk Education for Dementia (AGREEDementia). The framework developed by the Multi-Regional Clinical Trials (MRCT) Return of Individual Research Results provides a useful context for researchers to plan their studies and disclosure.

Communicating and Using Dementia Risk Evidence.

Advances in biomarkers, genetics, and other data used as dementia risk evidence (DRE) are increasingly informing clinical diagnosis and management. The purpose of this Mini-Forum is to provide a solutions-based discussion of the ethical and legal gaps and practical questions about how to use and communicate these data. Investigators often use DRE in research.

The Advisory Group on Risk Evidence Education for Dementia: Multidisciplinary and Open to All.

The brain changes of Alzheimer's disease and other degenerative dementias begin long before cognitive dysfunction develops, and in people with subtle cognitive complaints, clinicians often struggle to predict who will develop dementia. The public increasingly sees benefits to accessing dementia risk evidence (DRE) such as biomarkers, predictive algorithms, and genetic information, particularly as this information moves from research to demonstrated usefulness in guiding diagnosis and clinical management. For example, the knowledge that one has high levels of amyloid in the brain may lead one to seek amyloid reducing medications, plan for disability, or engage in health promoting behaviors to fight cognitive decline.

Repetitive Transcranial Magnetic Stimulation as a Treatment for Veterans with Cognitive Impairment and Multiple Comorbidities.

Background: Despite decades of research efforts, current treatments for Alzheimer's disease (AD) are of limited effectiveness and do not halt the progression of the disease and associated cognitive decline. Studies have shown that repetitive transcranial magnetic stimulation (rTMS) may improve cognition.

Objective: We conducted a pilot study to investigate the effect of rTMS on cognitive function in Veterans with numerous medical comorbidities.

Ruminative reflection is associated with anticorrelations between the orbitofrontal cortex and the default mode network in depression: implications for repetitive transcranial magnetic stimulation.

Patients with depression who ruminate repeatedly focus on depressive thoughts; however, there are two cognitive subtypes of rumination, reflection and brooding, each associated with different prognoses. Reflection involves problem-solving and is associated with positive outcomes, whereas brooding involves passive, negative, comparison with other people and is associated with poor outcomes. Rumination has also been related to atypical functional hyperconnectivity between the default mode network and subgenual prefrontal cortex.

Identifying cardiovascular risk factors that impact cerebrovascular reactivity: An ASL MRI study.

Background: To maintain cerebral blood flow (CBF), cerebral blood vessels dilate and contract in response to blood supply through cerebrovascular reactivity (CR).

Purpose: Cardiovascular (CV) disease is associated with increased stroke risk, but which risk factors specifically impact CR is unknown.

Study Type: Prospective longitudinal.

White matter hyperintensities in vascular contributions to cognitive impairment and dementia (VCID): Knowledge gaps and opportunities.

White matter hyperintensities (WMHs) are frequently seen on brain magnetic resonance imaging scans of older people. Usually interpreted clinically as a surrogate for cerebral small vessel disease, WMHs are associated with increased likelihood of cognitive impairment and dementia (including Alzheimer's disease [AD]). WMHs are also seen in cognitively healthy people.

Are Disease Modifying Treatments Enough? Improving Quality of Life in Late-Stage Patients.

The potential for successful disease modifying treatments for Alzheimer's disease (AD) opens up the possibility that there will be a large cohort of patients living with late-stage dementia and poor quality of life. There must thus be a parallel effort to leverage restorative therapies that improve quality of life in these patients. With the potential for stopping the onset of AD in new patients must come a commitment to those patients living with this chronic disability for many more years than first thought.

Autobiographical recall of personally familiar names and temporal information in e-mails: An automatic analytic approach using e-mail communications.

An important question that arises from autobiographical memory research is whether the variables that influence memory in the laboratory also drive memory for autobiographical episodes in real life. We explored this question within the context of e-mail communications and investigated the variables that influence recall for personally familiar names and temporal information in e-mails. We designed a Web-based program that analyzed each participant's year-old sent e-mail archive and applied textual analysis algorithms to identify a set of sentences likely to be memorable.

Convergence Analysis of Micro-Lesions (CAML): An approach to mapping of diffuse lesions from carotid revascularization.

Carotid revascularization (endarterectomy, stenting) prevents stroke; however, procedure-related embolization is common and results in small brain lesions easily identified by diffusion weighted magnetic resonance imaging (DWI). A crucial barrier to understanding the clinical significance of these lesions has been the lack of a statistical approach to identify vulnerable brain areas. The problem is that the lesions are small, numerous, and non-overlapping.

The Impact of Latino Values and Cultural Beliefs on Brain Donation: Results of a Pilot Study to Develop Culturally Appropriate Materials and Methods to Increase Rates of Brain Donation in this Under-Studied Patient Group.

Objectives: Increasing the number of Latino persons with dementia who consent to brain donation (BD) upon death is an important public health goal that has not yet been realized. This study identified the need for culturally sensitive materials to answer questions and support the decision-making process for the family.

Methods: Information about existing rates of BD was obtained from the Alzheimer's Disease Centers.

Repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant major depression (TRMD) Veteran patients: study protocol for a randomized controlled trial.

Background: Evaluation of repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant major depression (TRMD) in Veterans offers unique clinical trial challenges. Here we describe a randomized, double-blinded, intent-to-treat, two-arm, superiority parallel design, a multicenter study funded by the Cooperative Studies Program (CSP No. 556) of the US Department of Veterans Affairs.

Volume of subclinical embolic infarct correlates to long-term cognitive changes after carotid revascularization.

Objective: Carotid intervention is safe and effective in stroke prevention in appropriately selected patients. Despite minimal neurologic complications, procedure-related subclinical microemboli are common and their cognitive effects are largely unknown. In this prospective longitudinal study, we sought to determine long-term cognitive effects of embolic infarcts.

Microembolization is associated with transient cognitive decline in patients undergoing carotid interventions.

Objective: Carotid interventions are important in helping to reduce the risk of stroke for patients with high-grade carotid artery stenosis; however, subclinical cerebral microemboli can occur during these procedures. Associations have been found between the incidence of microemboli and postoperative decline in memory. We therefore sought to determine whether this decline persisted long-term and to assess changes in other cognitive domains.

Genetic Polymorphisms Influence Cognition in Patients Undergoing Carotid Interventions.

While carotid interventions help decrease the risk of stroke, nearly 40% of patients experience cognitive deterioration. Genetic polymorphism in apolipoprotein E (ApoE) and brain-derived neurotrophic factor (BDNF) have been implicated in cognitive impairment; however, it is unclear whether they may influence cognitive changes in patients undergoing carotid intervention. In this study, we seek to assess the role of genetic polymorphisms in carotid intervention-related cognitive change.

A Prospective Evaluation of Systemic Biomarkers and Cognitive Function Associated with Carotid Revascularization.

Objective: To determine factors affecting cognition and identify predictors of long-term cognitive impairment following carotid revascularization procedures.

Background: Cognitive impairment is common in older patients with carotid occlusive diseases.

Methods: Patients undergoing carotid intervention for severe occlusive diseases were prospectively recruited.

Brain structural connectivity distinguishes patients at risk for cognitive decline after carotid interventions.

While brain connectivity analyses have been demonstrated to identify ill patients for a number of diseases, their ability to predict cognitive impairment after brain injury is not well established. Traditional post brain injury models, such as stroke, are limited for this evaluation because pre-injury brain connectivity patterns are infrequently available. Patients with severe carotid stenosis, in contrast, often undergo non-emergent revascularization surgery, allowing the collection of pre and post-operative imaging, may experience brain insult due to perioperative thrombotic/embolic infarcts or hypoperfusion, and can suffer post-operative cognitive decline.

Longitudinal Cognitive Trajectories of Women Veterans from the Women's Health Initiative Memory Study.

Purpose Of The Study: A comparison of longitudinal global cognitive functioning in women Veteran and non-Veteran participants in the Women's Health Initiative (WHI).

Design And Methods: We studied 7,330 women aged 65-79 at baseline who participated in the WHI Hormone Therapy Trial and its ancillary Memory Study (WHIMS). Global cognitive functioning (Modified Mini-Mental State Examination [3MSE]) in Veterans (n = 279) and non-Veterans (n = 7,051) was compared at baseline and annually for 8 years using generalized linear modeling methods.