The Edinburgh Consensus: preparing for the advent of disease-modifying therapies for Alzheimer's disease

Abstract

Context: This commentary discusses the implications of disease-modifying treatments for Alzheimer's disease which seem likely to appear in the next few years and results from a meeting of British experts in neurodegenerative diseases in Edinburgh. The availability of such treatments would help change public and professional attitudes and accelerate engagement with the prodromal and preclinical populations who might benefit from them. However, this would require an updated understanding of Alzheimer's disease, namely the important distinction between Alzheimer's disease and Alzheimer's dementia.

Consensus: Since treatments are likely to be most effective in the early stages, identification of clinically relevant brain changes (for example, amyloid burden using imaging or cerebrospinal fluid biomarkers) will be crucial. While current biomarkers could be useful in identifying eligibility for new therapies, trial data are not available to aid decisions about stopping or continuing treatment in clinical practice. Therefore, effective monitoring of safety and effectiveness when these treatments are introduced into clinical practice will be necessary to inform wide-scale use. Equity of access is key but there is a tension between universal access for everyone with a diagnosis of Alzheimer's disease and specifying an eligible population most likely to respond. We propose the resources necessary for an optimal care pathway as well as the necessary education and training for primary and secondary care.

Conclusion: The majority of current services in the UK and elsewhere would not be able to accommodate the specialist investigations required to select patients and prescribe these therapies. Therefore, a stepped approach would be necessary: from innovating sentinel clinical-academic centres that already have capacity to deliver the necessary phase IV trials, through early adoption in a hub and spoke model, to nationwide adoption for true equity of access. The optimism generated by recent and anticipated developments in the understanding and treatment of Alzheimer's disease presents a great opportunity to innovate and adapt our services to incorporate the next exciting development in the field of dementia.

Keywords: Alzheimer’s disease; Clinical trials; Dementia; Disease-modification; Service redesign; Therapeutics.

Fig. 1

The continuum of Alzheimer’s disease pathology from the preclinical and prodromal stages to overt clinical dementia plus the relative importance of biomarker assessment and functional assessment at the different stages

Fig. 2

Hypothetical model of intervention with a disease-modifying treatment for Alzheimer’s disease. The curved line depicts a biomarker reflecting a specific drug target which responds to treatment. a depicts the courses of mechanism-specific drug(s). b depicts the accompanying tailored risk factor intervention and advice. The dotted grey line indicates the disease course without treatment—progressive functional deterioration. The solid grey line indicates the disease course with treatment—slower deterioration and better functional outcome, i.e. the delay of onset of clinical dementia. Adapted from Hampel et al. [12]