APOE4 allele modifies the effect of lifestyle interventions on cognition

Abstract Background The apolipoprotein E ε4 allele (APOE4) is the main genetic risk factor for incidence and earlier onset of dementia, and APOE4 carriers are thus considered a key target group for dementia risk reduction. APOE4 carriership also impacts the association between lifestyle and cognitive decline. Our meta-analysis investigated whether APOE4 modifies the effect of lifestyle intervention on cognition among people with elevated dementia risk in Finland (FINGER study), France (MAPT) and Japan (J-MINT). Methods We collected harmonised estimates from three completed randomised clinical trials investigating the effect of multidomain lifestyle interventions on cognitive decline. Age ranged from 60 to 85 years and risk for dementia was defined with dementia risk score (FINGER), subjective cognitive complaints or signs of frailty (MAPT), or mild cognitive impairment (J-MINT). The meta-analysis was based on random-effects model with maximum likelihood estimation. Results Here we show that the benefit of intervention is greater among APOE4 carriers than non-carriers after 12 months of intervention (interaction p = 0.039) and borderline significantly after 24 months ( p = 0.058) for global cognition. Among the cognitive domains, the APOE4 effect modification appears to be more related to executive function than memory or processing speed. Stratified analysis show that the intervention effect on global cognition and executive function is significant among APOE4 carriers at both 12 and 24 months. Conclusions Our results indicate that APOE4 carriers are a key target group for lifestyle-based prevention in people with mild cognitive impairment or earlier at-risk stages.