Baseline predictors of neurophysiological response to combined physical and cognitive training in older adults with subjective cognitive decline

Our previous study demonstrated that a 6-month combined physical and cognitive training program improved mismatch negativity (MMN)—an event-related potential reflecting the brain’s automatic detection of environmental changes—in older adults with subjective cognitive decline (SCD). However, not all individuals benefited equally from the intervention. Identifying baseline predictors of intervention outcomes could enable the prediction of individual responsiveness and support the development of personalized, stratified intervention strategies to promote brain health in this at-risk population. This study aimed to identify baseline predictors of response to a 6-month combined cognitive and physical training program among older adults with SCD. We conducted a secondary analysis of a cluster-randomized trial involving 33 older adults with SCD who participated in twice-weekly integrated training sessions. MMN was assessed for the analytic sample (n = 21) as the primary outcome measure. Baseline predictors included age, general cognitive function, physical and cognitive activity engagement, and apolipoprotein E (APOE) genotype. Linear regression analyses were performed to examine predictors of change in MMN amplitude from baseline to post-intervention. Regression analysis indicated that APOE ε4 non-carriers showed significantly greater improvement in MMN amplitude (β = ‒0.449, p = 0.027). Additionally, lower baseline levels of physical activity demonstrated a trend toward association with greater MMN gains (β = ‒0.392, p = 0.050), suggesting that individuals with more sedentary lifestyles may derive greater benefit from the intervention. APOE ε4 carrier status and baseline physical activity levels may be associated with the effectiveness of multidomain interventions in older adults with SCD.