Midlife Lifestyle Activities Moderate APOE ε4 Effect on in vivo Alzheimer’s Disease Pathologies

Jeon, So Yeon; Byun, Min Soo; Yi, Dahyun; Lee, Jun-Ho; Ko, Kang; Sohn, Bo Kyung; Lee, Jun-Young; Ryu, Seung‐Ho; Lee, Dong Woo; Shin, Seoung A; Kim, Yu Kyeong; Kang, Koung Mi; Sohn, Chul‐Ho; Lee, Dong Hoon

doi:10.3389/fnagi.2020.00042

Cited by 17 publications

(20 citation statements)

References 64 publications

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“…Using MRI, the morphology of the hippocampus-including volume and shape-can be characterized. The findings from cross-sectional studies utilizing physical activity questionnaires are mixed (see Table 2), with some studies reporting that greater engagement in physical activity is associated with greater hippocampal volume (Gorham et al, 2019;Hashimoto et al, 2017;Killgore et al, 2013;McEwen et al, 2015;Nunley et al, 2017;Okonkwo et al, 2014;Tarkka et al, 2019), and other studies reporting null results (Bugg & Head, 2011;Head et al, 2012;Jeon et al, 2020;M. Ortega et al, 2015;Vemuri et al, 2012).…”

Section: Hippocampal Morphologymentioning

confidence: 99%

“…Many other studies have reported similar findings across healthy and patient populations, including schizophrenia and Type 1 diabetes (Gorham et al, 2019; McEwen et al, 2015; Nunley et al, 2017; Okonkwo et al, 2014; Tarkka et al, 2019). Several studies of older adults (Bugg & Head, 2011; Head et al, 2012; Jeon et al, 2020; Vemuri et al, 2012) and adults with human immunodeficiency virus (M. Ortega et al, 2015) have failed to find similar associations, although Head and colleagues found decreased hippocampal volume among older adults with increased stress and lower physical activity levels (2012). These mixed findings might suggest that other unmeasured factors are either conflating or moderating the association.…”

Section: Hippocampal Morphologymentioning

confidence: 99%

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Aerobic exercise, cardiorespiratory fitness, and the human hippocampus

et al. 2021

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The hippocampus is particularly susceptible to neurodegeneration. Physical activity, specifically increasing cardiorespiratory fitness via aerobic exercise, shows promise as a potential method for mitigating hippocampal decline in humans. Numerous studies have now investigated associations between the structure and function of the hippocampus and engagement in physical activity. Still, there remains continued debate and confusion about the relationship between physical activity and the human hippocampus. In this review, we describe the current state of the physical activity and exercise literature as it pertains to the structure and function of the human hippocampus, focusing on four magnetic resonance imaging measures: volume, diffusion tensor imaging, resting-state functional connectivity, and perfusion.We conclude that, despite significant heterogeneity in study methods, populations of interest, and scope, there are consistent positive findings, suggesting a promising role for physical activity in promoting hippocampal structure and function throughout the lifespan.

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Section: Hippocampal Morphologymentioning

confidence: 99%

Section: Hippocampal Morphologymentioning

confidence: 99%

Aerobic exercise, cardiorespiratory fitness, and the human hippocampus

et al. 2021

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“…Although cerebrospinal fluid biomarkers and amyloid PET imaging are the most frequently applied modalities in this field, the applicability of plasma biomarkers is gradually improving. Many observational studies involving measures of Aβ in cerebrospinal fluid ( Liang et al, 2010 ; Brown et al, 2013 , 2017 ; Law et al, 2018 ), plasma ( Stillman et al, 2017 ), and PET ( Head et al, 2012 ; Brown et al, 2013 , 2017 ; Jeon et al, 2020 ; Treyer et al, 2021 ) have reported better profiles of amyloid-related biomarkers in active people but inconsistencies remain ( de Souto Barreto et al, 2015 ; Jeon et al, 2020 ; Palta et al, 2020 ; Stojanovic et al, 2020 ). The representative studies are summarized in Table 4 .…”

Section: Anti-neurodegenerative Mechanismsmentioning

confidence: 99%

Active Life for Brain Health: A Narrative Review of the Mechanism Underlying the Protective Effects of Physical Activity on the Brain

Umegaki

Sakurai

Arai

2021

Front. Aging Neurosci.

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A growing body of evidence clearly indicates the beneficial effects of physical activity (PA) on cognition. The importance of PA is now being reevaluated due to the increase in sedentary behavior in older adults during the COVID-19 pandemic. Although many studies in humans have revealed that PA helps to preserve brain health, the underlying mechanisms have not yet been fully elucidated. In this review, which mainly focuses on studies in humans, we comprehensively summarize the mechanisms underlying the beneficial effects of PA or exercise on brain health, particularly cognition. The most intensively studied mechanisms of the beneficial effects of PA involve an increase in brain-derived neurotrophic factor (BDNF) and preservation of brain volume, especially that of the hippocampus. Nonetheless, the mutual associations between these two factors remain unclear. For example, although BDNF presumably affects brain volume by inhibiting neuronal death and/or increasing neurogenesis, human data on this issue are scarce. It also remains to be determined whether PA modulates amyloid and tau metabolism. However, recent advances in blood-based biomarkers are expected to help elucidate the beneficial effects of PA on the brain. Clinical data suggest that PA functionally modulates cognition independently of neurodegeneration, and the mechanisms involved include modulation of functional connectivity, neuronal compensation, neuronal resource allocation, and neuronal efficiency. However, these mechanisms are as yet not fully understood. A clear understanding of the mechanisms involved could help motivate inactive persons to change their behavior. More accumulation of evidence in this field is awaited.

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“…Head et al suggested that APOE ε4 carriers with low exercise levels might have increased risk for cerebral Aβ deposition [ 47 ]. A recent study by Jeon et al investigated whether APOE ε4 status combined with high midlife physical activity could modify Aβ retention [ 48 ]. APOE ε4 carriers with a mean age of 72 years in a low physical activity state had higher Aβ accumulation, and this was absent in highly active carriers.…”

Section: Physical Activity In Apoe ε4 Carriersmentioning

confidence: 99%

Exercise as Potential Therapeutic Target to Modulate Alzheimer’s Disease Pathology in APOE ε4 Carriers: A Systematic Review

Tokgöz

Claassen

2021

Cardiol Ther

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Alzheimer’s disease (AD) is a progressive neurodegenerative disease for which no effective treatment exists at present. Previous research has found that exercise reduces the risk of AD. Since the apolipoprotein E (APOE) ε4 allele increases the risk of AD and is associated with faster disease progression than the other isoforms, we aimed to highlight the impact of exercise on AD pathology in APOE ε4 carriers. This review focuses on the effect of exercise on cognitive function, dementia risk, amyloid-β (Aβ) metabolism, lipid metabolism, neuroinflammation, neurotrophic factors and vascularization in APOE ε4 carriers. We searched the literature in the PubMed electronic database using the following search terms: physical activity, exercise, aerobic fitness, training, sport, APOE4, Alzheimer’s disease, AD and dementia. By cross-referencing, additional publications were identified. Selected studies required older adults to take part in an exercise intervention or to make use of self-reported physical activity questionnaires. All included studies were written and published in English between 2000 and 2020. From these studies, we conclude that exercise is a non-pharmacological treatment option for high-risk APOE ε4 carriers to ameliorate the AD pathological processes including reducing Aβ load, protecting against hippocampal atrophy, improving cognitive function, stabilizing cholesterol levels and lowering pro-inflammatory signals. Variation in study design related to age, cognitive outcomes and the type of intervention explained the differences in study outcomes. However, exercise seems to be effective in delaying the onset of AD and may improve the quality of life of AD patients.

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Midlife Lifestyle Activities Moderate APOE ε4 Effect on in vivo Alzheimer’s Disease Pathologies

Cited by 17 publications

References 64 publications

Aerobic exercise, cardiorespiratory fitness, and the human hippocampus

Aerobic exercise, cardiorespiratory fitness, and the human hippocampus

Active Life for Brain Health: A Narrative Review of the Mechanism Underlying the Protective Effects of Physical Activity on the Brain

Exercise as Potential Therapeutic Target to Modulate Alzheimer’s Disease Pathology in APOE ε4 Carriers: A Systematic Review

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