title: The benefits of staying active in old age: physical activity counteracts the negative influence of PICALM, BIN1, and CLU risk alleles on episodic memory functioning.
abstract: PICALM, BIN1, CLU, and APOE are top candidate genes for Alzheimer's disease, and they influence episodic memory performance in old age. Physical activity, however, has been shown to protect against age-related decline and counteract genetic influences on cognition. The aims of this study were to assess whether (a) a genetic risk constellation of PICALM, BIN1, and CLU polymorphisms influences cognitive performance in old age; and (b) if physical activity moderates this effect. Data from the SNAC-K population-based study were used, including 2,480 individuals (age range = 60 to 100 years) free of dementia at baseline and at 3- to 6-year follow-ups. Tasks assessing episodic memory, perceptual speed, knowledge, and verbal fluency were administered. Physical activity was measured using self-reports. Individuals who had engaged in frequent health- or fitness-enhancing activities within the past year were compared with those who were inactive. Genetic risk scores were computed based on an integration of risk alleles for PICALM (rs3851179 G allele, rs541458 T allele), BIN1 (rs744373 G allele), and CLU (rs11136000 T allele). High genetic risk was associated with reduced episodic memory performance, controlling for age, education, vascular risk factors, chronic diseases, activities of daily living, and APOE gene status. Critically, physical activity attenuated the effects of genetic risk on episodic memory. Our findings suggest that participants with high genetic risk who maintain a physically active lifestyle show selective benefits in episodic memory performance.
authors.affiliation: Aging Research Center, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet.
authors.forename: Beata
authors.initials: B
authors.lastname: Ferencz
authors.affiliation: Aging Research Center, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet.
authors.forename: Erika J
authors.initials: EJ
authors.lastname: Laukka
authors.affiliation: Aging Research Center, Department of NVS, Karolinska Institutet.
authors.forename: Anna-Karin
authors.initials: AK
authors.lastname: Welmer
authors.affiliation: Aging Research Center, Department of NVS, Karolinska Institutet.
authors.forename: Grégoria
authors.initials: G
authors.lastname: Kalpouzos
authors.affiliation: Aging Research Center, Department of NVS, Karolinska Institutet.
authors.forename: Sara
authors.initials: S
authors.lastname: Angleman
authors.affiliation: Aging Research Center, Department of NVS, Karolinska Institutet.
authors.forename: Lina
authors.initials: L
authors.lastname: Keller
authors.affiliation: Department NVS, KI-Alzheimer Disease Research Center, Karolinska Institutet.
authors.forename: Caroline
authors.initials: C
authors.lastname: Graff
authors.affiliation: Aging Research Center, Department of NVS, Karolinska Institutet.
authors.forename: Martin
authors.initials: M
authors.lastname: Lövdén
authors.affiliation: Aging Research Center, Department of NVS, Karolinska Institutet.
authors.forename: Lars
authors.initials: L
authors.lastname: Bäckman
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000502:physiology / Q000523:psychology*; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics; D051152:Clusterin / Q000235:genetics*; D003071:Cognition / Q000502:physiology; D015444:Exercise / Q000502:physiology*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D061212:Memory, Episodic; D008875:Middle Aged; D034041:Monomeric Clathrin Assembly Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D012307:Risk Factors; D013548:Sweden; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C101410:BIN1 protein, human; C495242:CLU protein, human; D051152:Clusterin; D034041:Monomeric Clathrin Assembly Proteins; D009687:Nuclear Proteins; C439003:PICALM protein, human; D025521:Tumor Suppressor Proteins