Creating an Unprotected Class: Addressing Legal Risks in the Era of Biologically-Defined Alzheimer's Disease.

Background: Documentation of preclinical biomarker tests for Alzheimer's disease (AD) in the medical record may expose patients to employment and insurance discrimination risks. There is a gap in research describing clinicians' approaches to documenting biomarker results. Objective: To evaluate discrimination risks faced by patients undergoing biomarker testing for AD through a qualitative analysis of clinician documentation practices. Methods: Semi-structured interviews using hypothetical patient scenarios. The qualitative analysis focused on interviewees' responses related to documentation and disclosure of results. Results: We collected and analyzed 17 interviews with dementia experts; and identified three approaches to documenting biomarkers as: an association with active AD, noninformative, and an increased susceptibility for AD. Those who associated biomarkers with active disease were more likely to favor disclosure to employers and insurers, which could increase discrimination risks. Conclusions: This study demonstrates the variety of documentation and disclosure practices likely to emerge for preclinical AD biomarker tests and highlights a need for guidelines in this area.

Informed Consent for the Human Research Subject with a Neurologic Disorder.

The doctrine of informed consent sits at the intersection of law, ethics, and neuroscience, posing unique challenges for human subject research involving neurological patients. These challenges are compounded by the variegated nature of both neurological injury and the law governing research consent. This article provides a framework for investigators likely to encounter subjects with some degree of neurological impairment, whose capacity to consent requires scrupulous assessment prior to enrollment in research trials. We consider several researches and disease contexts-from emergency epilepsy research to long-term dementia research-and clarify the ethical and legal principles governing consent for participation in each. We additionally explore empirical research on consent capacity and survey several areas of emerging ethical import that will require the attention of investigators in decades to come.

Hyperglycemia is associated with more severe cytotoxic injury after stroke.

Hyperglycemia is a common complication after ischemic stroke, but its link to worse outcome is not well understood. We hypothesized that hyperglycemia may reflect an impaired metabolic response that is associated with worse cytotoxic brain injury. We performed retrospective analysis of magnetic resonance imaging from a cohort of acute ischemic stroke patients prospectively collected from 2006 to 2010 with baseline demographic and laboratory data as well as three-month outcomes. The severity of cytotoxic injury was quantified in vivo using apparent diffusion coefficient imaging by measuring the signal intensity within the stroke relative to the normal signal intensity of the contralateral hemisphere. Both hyperglycemia and lower apparent diffusion coefficient signal were associated with worse outcome after ischemic stroke (OR 0.239, p = 0.017; OR 1.11, p < 0.0001, respectively). Hyperglycemia was also associated with lower apparent diffusion coefficient (r = -0.32, p < 0.001). In multivariate analysis, apparent diffusion coefficient but not hyperglycemia was associated with outcome, suggesting that cytotoxicity may mediate the effect of hyperglycemia. For interventions designed to target hyperglycemia in acute ischemic stroke, a concomitant effect on the evolution of apparent diffusion coefficient may provide insight into whether hyperglycemia leads to or reflects worse cytotoxic injury.