Research with Alzheimer's disease subjects: informed consent and proxy decision making

Because patients with Alzheimer's disease are on a path of declining capacity to give consent, advancement of research with Alzheimer's disease subjects presents challenging and perplexing ethical and legal dilemmas. Although generic regulations for the protection of human subjects apply, special considerations for cognitively impaired dementia subjects have depended on local Institutional Review Boards and relevant state laws and regulations, producing a lack of uniformity regarding encouragement of research and protection of subjects. Discussed are the dilemmas encountered in advancing research with Alzheimer's disease subjects, including (1) issues about informed consent, (2) determination of decision-making capacity (competency), (3) problems in dealing with subjects of mild and fluctuating impairment, and (4) proxy and advance consent measures for severely impaired subjects. Proposed is an agenda of ethical research needs for advancing biomedical research on Alzheimer's disease. Needed are empirical studies concerning recruitment of Alzheimer's disease subjects, the actual processes of informed consent, and the difficulties encountered by researchers, collaborative development of tests for both diagnosing Alzheimer's disease and assessing subjects' capacities to provide informed consent, and exploration of innovative uses of advance and proxy consents for participation in Alzheimer's disease research.