Table 3. Studies showing interaction between APOE gene polymorphism, physical exercise, and cognitive function.

Reference	Participants	Methodology	Type of study	Main findings
Smith et al. (2016) 49	Healthy individuals >65 years (n=88)	Level of PA Neuroimage Cognitive test Genotype for APOE	Longitudinal	High PA level has protective effect on neurodegeneration in patients who carry APOEε4 allele
Solomon et al. (2018) 50	Individuals >65 years APOEε4 carriers (n=362) APOEε4 non-carriers (n=747)	Multi-domain tasks Cognitive test Genotypes for APOE	Longitudinal	APOEε4 carriers or non-carriers are responsive to multi-domain tasks
Shih et al. (2018) 51	Individuals >60 years (n=1,438)	Level of PA Cognitive test Genotype for APOE	Longitudinal	Higher PA level mitigates dementia in APOEε4 allele carriers
Ferrari et al. (2013) 52	Individuals >75 years (n=932)	Educational level Leisure activities Genotypes for APOE	Longitudinal	Higher educational, lower vascular risk, and leisure activities diminish risk of dementia in patients who carry APOEε4 allele
Jensen et al. (2019) 53	Patients with AD >65 years APOEε4 carrier (n=17) APOEε4 non-carrier (n=5)	16 weeks of AET, 60 min, 3x/week, 70-80% HR reserve Cognitive and motor tests Genotype for APOE	Longitudinal	APOEε4 allele carriers are more responsive to AET than non-carriers
Fenesi et al. (2017) 54	Healthy individuals >65 years (n=1,646)	PA levelGenotype for APOE	Longitudinal	Physical exercise had no effect on dementia in patients who carry APOEε4 allele
Stern et al. (2019) 55	Individuals 20-67 years (n=132)	AET Cognitive test Genotype for APOE	Longitudinal	AET does not modify the score of cognitive tests in APOEε4 carriers
Allard et al. (2017) 56	Individuals with MCI >55 years (n=21)	AET for 6 months Genotype for APOEBDNF level	Longitudinal	No changes in BDNF level after AET in APOEε4 carriers

PA: physical activity; AD: Alzheimer's disease; BDNF: brain-derived neurotrophic factor; HR: heart rate; AET: aerobic exercise training; MCI: mild cognitive impairment.