APOE genotype, hippocampal volume, and cognitive reserve predict improvement by cognitive training in older adults without dementia: a randomized controlled trial

Abstract

Cognitive training (CT) programs aim to enhance cognitive performance and prevent decline. Identifying individual characteristics that predict CT effectiveness is crucial. This study examined whether cognitive reserve (CR), APOE genotype (e4 carriers/non-carriers), and hippocampal volume influence CT outcomes. A total of 226 older adults without dementia were randomized into experimental-control groups. Assessments included neuropsychological testing, brain volume measurements, APOE-genotype, and CR evaluation. The intervention consisted of 30 multifactorial CT sessions over six months, while the control group followed routine activities. Results showed that APOE-e4 non-carriers (79.1%) with larger left hippocampal volume had greater gains in semantic verbal fluency (R² = .19). Higher CR and greater gray matter volume were associated with improved processing speed (R² = .18). Age negatively correlated with executive function improvement (R² = .07). These findings highlight that CT effectiveness depends on age, genetic profile, brain structure, and CR, emphasizing the need for personalized interventions.