Interaction between physical exercise and APOE gene polymorphism on cognitive function in older people

Colovati, M.E.S.; Novais, I.P.; Zampol, M.; Mendes, G.D.; Cernach, M.C.S.; Zanesco, A.

doi:10.1590/1414-431X202010098

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Brazilian Journal of Medical and Biological Research

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Review • Braz. J. Med. Biol. Res. 54 (2) • 2021 • https://doi.org/10.1590/1414-431X202010098 copy

Interaction between physical exercise and APOE gene polymorphism on cognitive function in older people

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We aimed to present an overview of the literature regarding the interaction between physical exercise and APOE gene polymorphism on cognitive function, particularly in patients with Alzheimer's disease (AD). Firstly, this review focused on the effect of the physical exercise on cognitive function, regardless of APOE gene polymorphism. Some studies have shown that a high level of cardiorespiratory fitness is associated with less neuronal damage with an improvement in memory score tests whereas other studies failed to detect any association between physical exercise and cognitive improvement either in healthy individuals or patients with AD. Taken together, standardized protocols and more longitudinal studies are required to provide a better insight into the effects of physical exercise on cognitive function. Although there is no agreement in the literature regarding the effects of physical exercise on cognitive function, it is well established that it improves social interaction and the feeling of well-being, thereby positively contributing to the quality of life of the elderly. Regarding the influence of physical exercise on cognitive function in APOE ε4 allele carriers, the data trend shows that the carriers of allele ε4 for APOE gene were more responsive to the beneficial effects of physical exercise on cognitive function compared with non-carriers. Nevertheless, studies with larger sample sizes will provide more accuracy about this relationship.

Alzheimer’s disease; Exercise; Cognition; Apolipoproteins E; Genetic polymorphism; Aged

Reference	Participants	Methodology	Type of study	Main findings
Ainslie et al. (2008) 30	Healthy men PA >2 years (n=153) PI >2 years (n=154)	Cerebral blood flow by Doppler VO₂max	Cross-sectional	Improvement of the cerebral blood flow in PA compared with PI individuals
Boyle et al. (2015) 31	963 participants >65 years. 10% with AD, MCI, control	MRI scan BMI measurements Level of physical activity	Longitudinal	High level of PA was associated with higher brain volume Higher BMI was inversely correlated with cerebral volume
Perea et al. (2016) 32	Individuals with AD >55 years PA (n=40) PI (n=37)	26 weeks of physical exercise MRI scan VO₂max	Longitudinal	Higher level of CRF was associated with white brain mass integrity
Morris et al. (2017) 33	Individuals >65 years PA (n=34) PI (n=34)	MRI scan VO₂max	Longitudinal	Improvement in CRF was associated with better cognitive test score and reduction of hippocampus atrophy
Schultz et al. (2015) 34	Individuals >65 years (n=69)68% women 72% family history of AD	βA42 level in the CSF PET scan VO₂max	Cross-sectional	Positive relationship between VO₂ peak and βA42 levels
Law et al. (2018) 35	Individuals >55 years (n=85) 61% women 81% family history of AD	Accelerometer for 7 days Levels of βA42 and tau in CSF	Longitudinal	Physical activity was associated with increment in βA42 and lower rate of p-tau/βA42
Holthoff et al. (2015) 36	Patients with AD >65 years 50% women Exercise training (n=15) Control (n=15)	12 weeks of exercise training Cognitive and motor tests	Longitudinal	Improvement of cognitive and motor functions in trained group
Sobol et al. (2018) 37	Patients with MCI: 50-90 years Physical exercise (n=26) Control (n=23)	16 weeks of exercise training Cognitive test VO₂max	Longitudinal	Improvement in VO₂max was associated with better score of cognitive tests in trained group
Seifert et al. (2010) 39	Young men Physical exercise (n=7) Control (n=5)	Three months of exercise training Plasma BDNFVO₂max	Longitudinal	Higher VO₂max was associated with increment in BDNF levels in trained group

Reference	Participants	Methodology	Type of study	Main findings
Brasure et al. (2018) 41	16 articles (2009-2017)	Systematic review Patients with AD vs control underwent physical activity for 6 months	Longitudinal	Failed to find an association between physical activity and cognitive function
van der Kleij et al. (2018) 42	Patient with mild or moderate AD >65 years 40% women Exercise training (n=27) Control (n=24)	16-week exercise training, 60min, 3x-week, 70-80% HRR MRI scan VO₂max	Longitudinal	Greater VO₂max in trained group,no change in cerebral blood flow between groups or MEEM score
Jensen et al. (2017) 43	Patients with AD >65 years 48% women Exercise training (n=25) Control (n=26)	16-week exercise training CSF for measurements of biomarkers	Longitudinal	Exercise training did not promote any changes in the brain damage biomarkers or neuroinflammation
Frederiksen et al. (2019) 44	Jan/1984 to Feb/2018 34 studies/healthy participants 3 studies/healthy/MCI participants 1 study/MCI participants 2 studies/AD patients	Systematic review Biomarkers, MRI scan, PET	Longitudinal	No association between physical exercise and cognitive function
Vidoni et al. (2013) 48	Individuals 60-85 years ESAD (n=16) Control (n=18)	MRI scan VO₂max Motor tests	Cross-sectional	Cardiorespiratory fitness was associated with improvement in brain activity in control group but not in patients with ESAD

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

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[1] Correspondence: A. Zanesco: <angelina.zanesco@gmail.com>