APOE Moderates the Association between Lifestyle Activities and Cognitive Performance: Evidence of Genetic Plasticity in Aging

Abstract

The current study examined independent and interactive effects between Apolipoprotein E (APOE) genotype and two types of cognitively-stimulating lifestyle activities (CSLA)—integrated information processing (CSLA-II) and novel information processing (CSLA-NI)—on concurrent and longitudinal changes in cognition. Three-wave data across six years of follow-up from the Victoria Longitudinal Study (n = 278; ages 55–94) and linear mixed model analyses were used to characterize the effects of APOE genotype and participation in CSLA-II and CSLA-NI in four cognitive domains. Significant CSLA effects on cognition were observed. More frequent participation in challenging activities (i.e., CSLA-NI) was associated with higher baseline scores on word recall, fact recall, vocabulary and verbal fluency. Conversely, higher participation in less cognitively-challenging activities (i.e., CSLA-II) was associated with lower scores on fact recall and verbal fluency. No longitudinal CSLA-cognition effects were found. Two significant genetic effects were observed. First, APOE moderated CSLA-II and CSLA-NI associations with baseline verbal fluency and fact recall scores. Second, APOE ε4 non-carriers’ baseline performance were more likely to be moderated by CSLA participation, compared to APOE ε4 carriers. Our findings suggest APOE may be a “plasticity” gene that makes individuals more or less amenable to the influence of protective factors such as CSLA.

Cognitive activity mediates the association between social activity and cognitive performance: A longitudinal study.

“…Cognitive activities may be a way to maintain cognitive function in older adulthood, a principle summarized by the adage “use it or lose it” (Bielak, 2010; Hertzog et al, 2008; Hultsch et al, 1999). However, this effect may be moderated by biological or genetic risk factors (Runge, Small, McFall, & Dixon, 2014). “Use it or lose it” is a principle of experience-dependent brain plasticity such that synaptic connections that are not sufficiently engaged will weaken and be lost over time (Kleim & Jones, 2008).…”

Apolipoprotein E and Clusterin can magnify effects of personality vulnerability on declarative memory performance in non‐demented older adults

“…Previous reports have shown that neuroticism levels discriminate between healthy aging and early‐stage AD (Duchek et al ., ), and an active lifestyle may act as a buffer against the negative effects of high neuroticism in at‐risk adults (Wang et al ., ). The present sample may have benefited from both healthy aging, with lower neuroticism levels, and a relatively advantaged socially engaged lifestyle (Runge et al ., ). Whether lifestyle activities play a specific role in this gene–personality dynamic should be tested in future studies.…”

“…Genetic association studies have been useful in identifying the degree of risk associated with some alleles in selected SNPs for cognitive changes with aging (Kremen and Lyons, 2011). However, for many neurocognitive phenotypes, the consideration of personal attributes and lifestyle activities may supplement or modify the observed roles of biological (genetic) factors (Runge et al, 2014;Sachs-Ericsson et al, 2010;Shanahan and Hofer, 2005). Personality traits encompass a wide range of behaviors as typically summarized in a specific set of dimensions or patterns characteristic to given individuals, and they are generally stable in adulthood (Soubelet and Salthouse, 2011).…”

Risk- and protective factors for memory plasticity in aging

“…Additionally, APOE allelic variation has been assumed to relate to plastic responses to cognitive training interventions. Although results are inconclusive, it has been suggested that ε4 carriers may show less cognitive plasticity than non-carriers (Feng et al, 2015;Polito et al, 2015;Runge, Small, McFall, & Dixon, 2014;Zehnder et al, 2009). As the prevalence of people living with dementia is increasing (Livingston et al, 2017), it is of interest to study whether genetic variation, IQ, and modifiable lifestyle factors impact memory plasticity in a controlled experimental intervention.…”