Cognitive frailty, a novel target for the prevention of elderly dependency

• The paper updates a pre-existing clinical syndrome of cognitive frailty.
• Reversible cognitive frailty is a subtype of cognitive frailty.
• Pre-MCI SCD is proposed as a cognitive alteration of cognitive frailty.
• We outline the probable mechanisms of cognitive frailty due to physical causes.
• We detail the criteria for the screening and prevention of cognitive frailty.

Frailty is a complex and heterogeneous clinical syndrome. Cognitive frailty has been considered as a subtype of frailty. In this study, we refine the definition of cognitive frailty based on existing reports about frailty and the latest progress in cognition research. We obtain evidence from the literature regarding the role of pre-physical frailty in pathological aging. We propose that cognitive impairment of cognitive frailty results from physical or pre-physical frailty and comprises two subtypes: the reversible and the potentially reversible. Reversible cognitive impairment is indicated by subjective cognitive decline (SCD) and/or positive fluid and imaging biomarkers of amyloid-β accumulation and neurodegeneration. Potentially reversible cognitive impairment is MCI (CDR = 0.5). Based on the severity of cognitive impairment, it is possible to determine the primary and secondary preventative measures for cognitive frailty. We further determine whether SCD is a component of pre-clinical AD or the early stage of other neurodegenerative diseases, which is required for guiding personal clinical intervention.