Behavioural Brain Research · Jul 15, 2025
Joint association of cognitive reserve and frailty with incident Alzheimer's disease and related dementias
By Zhang YY, Han BL, Ma LZ et al.
Cognitive reserve and frailty are factors associated with Alzheimer's disease and related dementias (ADRD). However, whether cognitive reserve and frailty interact to influence ADRD has not been explored well. We included 908 participants from the ADNI study. Our results suggested that cognitive reserve interacted with frailty to influence ADRD risk. High cognitive reserve was associated with lower ADRD risk in both non-frail and mildly frail participants (P value < 0.001), but the association was not observed in severely frail participants. Furthermore, mediation analysis showed that cognitive reserve influence dementia risk partly through the modulation of AD biomarkers in non-frail and mildly frail participants. Our study demonstrated that high cognitive reserve decreased the risk of ADRD by modulating AD pathology in non-frail and mildly frail participants.