FRAILTY AND NEURODEGENERATIVE DISEASE: ANTICIPATING THE FUTURE, EXPANDING THE FRAMEWORK

The terminology surrounding frailty has grown increasingly popular for health care professionals and developers of technology over the last decades. Its concepts are useful in medical care, R&D, as well as in ethical assessment, and identify and define stages of age-related physical decline (1-5). Simultaneously, the phenomena of age-related cognitive decline and neurodegenerative diseases continue to pose a threat to older populations (6-8). Recognizing that physical frailty often co-occurs with cognitive decline, the concept of cognitive frailty is currently being developed (9-13). The terminology surrounding cognitive frailty is facilitating to bridge the gap between physical frailty and cognitive decline. However, it fails to capture important aspects of age-related neural decline and disease, that need to be addressed and included in a nuanced frailty-terminology. This matter is becoming increasingly urgent, as a growing number of promising technologies for neurodegenerative diseases are currently being developed. Nanotheranostics and Lab-on-a-chip devices, able to cross the blood-brain-barrier and analyze sample sizes as small as picolitres, may be able to detect neural decline at pre-symptomatic stages (14-16). This would facilitate early intervention, which is particularly important for preventing neurodegenerative diseases. Furthermore, the possibility of providing chip-based point-of-care devices for GPs would improve the accessibility to diagnosis for the general population (17). Additionally, neural bioprinting, optogenetics, and other innovative approaches to regenerative therapeutic neuromodulation raises hope that neural damage caused by decline and disease may be repaired (18-19).