Anti-amyloid therapies as a stress test for the effectiveness and sustainability of health systems engaged against Alzheimer's disease

The most relevant message emerging from the paper by Filippi and colleagues,¹ is the complexity of the actions needed, in the real-world setting, to achieve timely diagnosis and optimal treatment of patients with early Alzheimer's disease (AD). Such complexity starts from the periphery–patients, their families, and general practitioners (GPs)–and finds its operational headquarters in expert centres dedicated to the early diagnosis of AD.

We are living in an extremely exciting time, in which disease-modifying treatments for halting AD–namely anti-amyloid monoclonal antibodies–are available to eligible patients.^2,3 These treatments are highly costly and not devoid of side effects. The appropriateness of their use, together with their efficacy, will determine their fate and acceptance, as well as the future development of other pharmacological approaches.

To realise an effective patient journey aimed at achieving an early and accurate diagnosis finalised to treatment eligibility, several mandatory premises must be met: (i) investment in educational initiatives to improve awareness and collaboration among GPs, who need better knowledge of AD pathophysiology and of the importance of early and accurate diagnosis. Accordingly, in their routine evaluation of patients aged 60 years and over, they should pay attention to cognitive functions by systematically asking whether everything is going well with memory and functional abilities, rather than waiting for patients’ complaints. This simple action might contribute to reducing the issue of late diagnosis; (ii) the availability, for each territorial area, of expert centres guaranteeing biological profiling, dedicated neurologists, and facilities for treatment; (iii) neuroimaging services specifically trained in safety monitoring and in continuous communication with the expert centre; and (iv) clear and effective collaboration between regional health system delegates and the specialists involved.

The paper also addresses the use of plasma biomarkers as a tool for the triage of patients who are candidates for further diagnostic assessment (i.e., cerebrospinal fluid analysis). Ideally, this type of triage could be implemented within primary care services, a setting for which supportive evidence is already available in the literature.⁴ This represents an important opportunity that should not be missed, as it may facilitate and streamline the entry of patients into the pathway towards biological diagnosis. Further, this approach would favour the direct engagement of GPs in the patient journey.

Beyond these considerations, there are ethical and cultural issues concerning the crucial importance of informative communication at each step of the patient journey towards treatment–namely, between GP and patient, between GPs and specialists, between specialists and patients, and between specialists and health officers. This is a relatively unexplored field with tremendously important implications. Maintaining a clear, correct, and coherent narrative throughout the entire patient journey represents a key factor in providing the best possible service to patients and their families. Fluid communication among all actors involved means a great deal for the recipient of care. For this reason, it should be considered whether to adopt similar approaches and types of explanations across centres, in order to develop a form of guidance also addressing this aspect.

The final consideration refers to the broader field of disease-modifying treatments in neurodegenerative diseases evolving to dementia. At present, we are referring to anti-amyloid therapies administered to symptomatic AD patients.^2,3 In the future, the goal will be to treat, ideally, each biological actor involved, hopefully when the individual is biologically positive and still asymptomatic.⁵

Accordingly, much work remains to be done in this direction. Communication and education are our main tools to increase awareness of this extraordinary adventure in the treatment of dementia disorders. Filippi and his group have timely moved from the “pre-ordered” scenario of clinical trials to the real-world treatment of eligible AD patients.¹ This represents the first step of this exciting coalition against dementia.

Contributors

LP: conceptualization of commentary, draft of commentary and review of the literature.

LG: draft of commentary and review of the literature.

Declaration of interests

LP participated on advisory boards for and received speaker or writing honoraria and funding for travelling from Bayer, Biogen Idec, Genzyme, Merck, Mylan, Novartis, Roche, Siemens Healthineers and Teva. LG participated on advisory boards for, and received writing honoraria, speaker honoraria and travel grants from Almirall, Biogen, Euroimmun, Fujirebio, Merck, Mylan, Novartis, Roche, Sanofi, Siemens Healthineers and Teva.