Biomarkers sensitive to functional impairment, neuronal loss, tau, and amyloid pathology based on MR, PET, and CSF studies are increasingly used to diagnose Alzheimer's disease (AD), but clinical validation is incomplete, hampering reimbursement by payers, widespread clinical implementation, and impacting on health care quality. An expert group convened to develop a strategic research agenda to foster the clinical validation of AD biomarkers. These demonstrated sufficient evidence of analytical validity (phase I of a structured framework adapted from oncology). Research priorities were identified based on incomplete clinical validity (phases II and III), and clinical utility (phases IV and V). Priorities included: definition of the assays; reading procedures and thresholds for normality; performance in detecting early disease; accounting for the effect of covariates; diagnostic algorithms comprising combinations of biomarkers; and developing best practice guidelines for the use of biomarkers in qualified memory clinics in the context of phase IV studies. 5 GlossaryBiomarker. An objective measure of a biological or pathogenic process with the purpose of evaluating disease risk or prognosis, guiding clinical diagnosis or monitoring therapeutic interventions. While the term originally referred to traceable substances produced by or introduced into an organism, it later evolved to any measurable parameter, including those obtained via imaging procedures.Roadmap. Objective-oriented, structured, and efficient action plan. In science and technology also called "strategic research agenda".Alzheimer's disease (AD) dementia. Traditionally and according to the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria, Alzheimer's disease was defined as a syndrome with progressive cognitive impairment severe enough to impact on daily activities. A diagnosis of Alzheimer's disease could only be made after exclusion of other possible causes. 1 Sixty-five to 80% of cases of patients fulfilling these criteria have Alzheimer's pathology (plaques and tangles), the remainder having a range of other pathologies. In order to increase diagnostic certainty, contemporary criteria for AD dementia incorporate biomarker evidence for different aspects of Alzheimer's pathology, including imaging (magnetic resonance imaging -MRI -measures of atrophy; 18 F-fluorodeoxyglucose-positron emission tomography -FDG-PET -measures of cerebral hypometabolism; amyloid PET measures of fibrillar β-amyloid -A -deposition) and cerebrospinal fluid -CSF (decreased levels of A42, increased levels of tau and phospho-tau). 2,3 Alzheimer's disease process. Recognizing that AD pathology is present many years before symptoms emerge, new criteria classify the disease process on a continuum from asymptomatic to prodromal and finally to dementia stage. 4 Individuals at the asymptomatic stage can only be identified by biomarkers of Alzheimer's pathology. None...

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There is great interest in the use of biomarkers to assist in the timely identification of Alzheimer's disease (AD) in individuals with mild symptoms. However, the inclusion of AD biomarkers in clinical criteria poses socioethical challenges. The Geneva Task Force for the Roadmap of Alzheimer's Biomarkers was established to deliver a systematic strategic research agenda (aka roadmap) to promote efficient and effective validation of AD biomarkers and to foster their uptake in clinical practice. In this article, we summarize the workshop discussion of the Geneva Task Force "ethical and societal issues" working group, which comprised bioethicists, clinicians, health economists, and representatives of those affected by AD. The working group identified the following key issues that need to be included in the roadmap: improving access to services through timely diagnosis, the need for a diagnostic research protocol before moving to clinical routine, recruitment in diagnostic research protocols in the absence of effective therapy, respect for the autonomy of the individual with mild cognitive impairment in information and consent process and the right not to know biomarkers results, need for counseling programs, disclosure of the diagnosis in a structured environment and the involvement of family members, health policies including the individuals' views and the protection of their interests, and the economic costs for society.

This review indicates that high quality studies are needed that especially evaluate staff behaviours and patient outcomes and their sustainability over time. It also highlights measures that could be used to develop and deliver training programmes in hospital settings.