Physical activity and cognitive decline: The role of the apolipoprotein e4 allele

The National Institute of Public Health and the Environment, 3720 BA Bilthoven, The Netherlands.
Medicine & Science in Sports & Exercise (Impact Factor: 3.98). 05/2001; 33(5):772-7. DOI: 10.1097/00005768-200105000-00015
Source: PubMed


The purpose of this study was to investigate the association between level of physical activity and risk of cognitive decline at older age and its variation across carriers and noncarriers of the apolipoprotein e4 allele.
The association was studied in a cohort of 347 elderly Dutch men. Mean age of the study subjects was 74.6 +/- 4.3 yr in 1990. Physical activity was categorized in "maximal 1 h per day" versus "more than 1 h per day." Cognitive decline was defined as a drop MMSE score > 3 points between 1990 and 1993.
After adjusting for age, education, alcohol consumption, smoking and cognitive functioning at baseline, subjects with maximal 1 h of physical activity per day had a two-fold increased risk of cognitive decline (OR 2.0, 95% CI: 0.9-4.8) as compared with the rest. Risk of cognitive decline was particularly strong in carriers of the APOE*4 allele (adjusted OR 3.7, 95% CI: 1.1-12.6).
The authors conclude that promotion of physical activity at older age may reduce the risk of cognitive decline. The existence of subgroups with a particularly high risk may have important implications for prevention strategies.

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    • "Cross-sectional studies have reported differences between high and low PA on cognitive outcomes (Woodard et al., 2012; Smith et al., 2013), amyloid burden (Head et al., 2012), and brain function (Smith et al., 2011) in APOE-ε4 carriers (although see Lindsay et al., 2002). One such study (Schuit et al., 2001) reported reduced odds for experiencing cognitive decline in physically active older male APOE-ε4 carriers compared to sedentary carriers. Another study (Rovio et al., 2005) reported reduced odds of receiving an AD diagnosis in physically active male and female APOE-ε4 carriers compared to inactive carriers. "
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    ABSTRACT: We examined the impact of physical activity (PA) on longitudinal change in hippocampal volume in cognitively intact older adults at varying genetic risk for the sporadic form of Alzheimer's disease (AD). Hippocampal volume was measured from structural magnetic resonance imaging (MRI) scans administered at baseline and at an 18-month follow-up in 97 healthy, cognitively intact older adults. Participants were classified as High or Low PA based on a self-report questionnaire of frequency and intensity of exercise. Risk status was defined by the presence or absence of the apolipoprotein E-epsilon 4 (APOE-ε4) allele. Four subgroups were studied: Low Risk/High PA (n = 24), Low Risk/Low PA (n = 34), High Risk/High PA (n = 22), and High Risk/Low PA (n = 17). Over the 18 month follow-up interval, hippocampal volume decreased by 3% in the High Risk/Low PA group, but remained stable in the three remaining groups. No main effects or interactions between genetic risk and PA were observed in control brain regions, including the caudate, amygdala, thalamus, pre-central gyrus, caudal middle frontal gyrus, cortical white matter (WM), and total gray matter (GM). These findings suggest that PA may help to preserve hippocampal volume in individuals at increased genetic risk for AD. The protective effects of PA on hippocampal atrophy were not observed in individuals at low risk for AD. These data suggest that individuals at genetic risk for AD should be targeted for increased levels of PA as a means of reducing atrophy in a brain region critical for the formation of episodic memories.
    Full-text · Article · Apr 2014 · Frontiers in Aging Neuroscience
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    • "However, there are several moderating factors that share characteristics with physical activity or have similar putative mechanisms or pathways underlying the effects that provide researchers with a theoretical platform to begin their investigation. Along these lines, pertinent moderators of the effects of physical activity on brain health include (1) genotypes, such as apolipoprotein E (APOE) [21], brain derived neurotrophic factor (BDNF) [22], and catechol-O-methyltransferase (COMT) [23] because these genes influence molecular pathways thought to be regulated by physical activity and (2) dietary variables, such as omega-3 fatty acids [24] that share molecular mechanisms and behavioral outcomes with physical activity. Although there are clearly other factors that are moderating the effects of physical activity on neural outcomes, we will focus this paper on these few moderators for which there is empirical support for their effects. "
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    ABSTRACT: Age-related cognitive decline is linked to numerous molecular, structural, and functional changes in the brain. However, physical activity is a promising method of reducing unfavorable age-related changes. Physical activity exerts its effects on the brain through many molecular pathways, some of which are regulated by genetic variants in humans. In this paper, we highlight genes including apolipoprotein E (APOE), brain derived neurotrophic factor (BDNF), and catechol-O-methyltransferase (COMT) along with dietary omega-3 fatty acid, docosahexaenoic acid (DHA), as potential moderators of the effect of physical activity on brain health. There are a growing number of studies indicating that physical activity might mitigate the genetic risks for disease and brain dysfunction and that the combination of greater amounts of DHA intake with physical activity might promote better brain function than either treatment alone. Understanding whether genes or other lifestyles moderate the effects of physical activity on neurocognitive health is necessary for delineating the pathways by which brain health can be enhanced and for grasping the individual variation in the effectiveness of physical activity interventions on the brain and cognition. There is a need for future research to continue to assess the factors that moderate the effects of physical activity on neurocognitive function.
    Full-text · Article · Dec 2012 · Journal of aging research
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    • ", but not all [8] [9] [10] [11], longitudinal epidemiologic studies have shown a decreased risk of incident dementia or Alzheimer's disease (AD) in individuals who exercise regularly. Other studies have examined the effects of physical exercise on cognitive decline, with most demonstrating beneficial effects [12] [13] [14] [15] [16] [17]. Observational studies [18] [19] as well as randomized trials [20] [21] have provided evidence that physical activity, particularly that leading to improved cardiorespiratory fitness, is associated with increased brain tissue volumes. "
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    ABSTRACT: Physical exercise has been shown to increase brain volume and improve cognition in randomized trials of non-demented elderly. Although greater social engagement was found to reduce dementia risk in observational studies, randomized trials of social interventions have not been reported. A representative sample of 120 elderly from Shanghai, China was randomized to four groups (Tai Chi, Walking, Social Interaction, No Intervention) for 40 weeks. Two MRIs were obtained, one before the intervention period, the other after. A neuropsychological battery was administered at baseline, 20 weeks, and 40 weeks. Comparison of changes in brain volumes in intervention groups with the No Intervention group were assessed by t-tests. Time-intervention group interactions for neuropsychological measures were evaluated with repeated-measures mixed models. Compared to the No Intervention group, significant increases in brain volume were seen in the Tai Chi and Social Intervention groups (p < 0.05). Improvements also were observed in several neuropsychological measures in the Tai Chi group, including the Mattis Dementia Rating Scale score (p = 0.004), the Trailmaking Test A (p = 0.002) and B (p = 0.0002), the Auditory Verbal Learning Test (p = 0.009), and verbal fluency for animals (p = 0.01). The Social Interaction group showed improvement on some, but fewer neuropsychological indices. No differences were observed between the Walking and No Intervention groups. The findings differ from previous clinical trials in showing increases in brain volume and improvements in cognition with a largely non-aerobic exercise (Tai Chi). In addition, intellectual stimulation through social interaction was associated with increases in brain volume as well as with some cognitive improvements.
    Full-text · Article · Mar 2012 · Journal of Alzheimer's disease: JAD
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