Designing the next-generation clinical care pathway for Alzheimer's disease

Abstract

The reconceptualization of Alzheimer's disease (AD) as a clinical and biological construct has facilitated the development of biomarker-guided, pathway-based targeted therapies, many of which have reached late-stage development with the near-term potential to enter global clinical practice. These medical advances mark an unprecedented paradigm shift and requires an optimized global framework for clinical care pathways for AD. In this Perspective, we describe the blueprint for transitioning from the current, clinical symptom-focused and inherently late-stage diagnosis and management of AD to the next-generation pathway that incorporates biomarker-guided and digitally facilitated decision-making algorithms for risk stratification, early detection, timely diagnosis, and preventative or therapeutic interventions. We address critical and high-priority challenges, propose evidence-based strategic solutions, and emphasize that the perspectives of affected individuals and care partners need to be considered and integrated.

Fig. 1 |. The next-generation clinical care pathway for Alzheimer’s disease.

a, An overarching illustration. The next-generation clinical care pathway begins with healthy aging and participation in preventive lifestyle measures to slow or prevent accumulation of AD pathophysiology, with the goal of extending healthspan across populations. Symptom detection, triggered by concerned individuals or family members, or detected during a routine wellness visit, may involve cognitive testing and, in the future, blood-based biomarkers and digitally based assessments. This will be accompanied by clinical assessments involving standard laboratory tests and physical examination. Any recorded cognitive impairment will be confirmed with standardized biomarker tests. Individuals with confirmed disease will proceed to treatment initiation with relevant AD therapy followed by long-term monitoring, of which digital technologies and blood-based biomarkers will play a key role in the future. b, Digital health technologies in future AD clinical care and the path toward a precision monitoring and detection platform. A precision monitoring and detection platform will require a transformation from the traditional data collection methods to the inclusion of digital technologies. This will include active engagement technologies that require individual interaction and engagement to passive engagement technologies that collect data in the background while the individuals keep to their daily routine. AI, artificial intelligence; EEG, electroencephalogram; NP, neuropsychiatric; PSG, polysomnography.

Evolution of the diagnostic criteria for Alzheimer’s disease.

This timeline highlights key milestones in the development and updates to the diagnostic criteria for AD, the biological and clinical requirements that accompany their use, and their applicability in research and clinical settings. ADRDA, Alzheimer’s Disease and Related Disorders Association (now the Alzheimer’s Association) Work Group. IWG, International Working Group; NIA-AA, US National Institute on Aging and Alzheimer’s Association; NINCDS, National Institute of Neurological and Communicative Disorders and Stroke. Cognitively unimpaired individuals are considered at risk for AD. Schematic is based on the information in ref..