Dataset Information

Apolipoprotein E Genotype Moderation of the Association Between Physical Activity and Brain Health. A Systematic Review and Meta-Analysis.

ABSTRACT:

Introduction

Possession of one or two e4 alleles of the apolipoprotein E (APOE) gene is associated with cognitive decline and dementia risk. Some evidence suggests that physical activity may benefit carriers of the e4 allele differently.

Method

We conducted a systematic review and meta-analysis of studies which assessed APOE differences in the association between physical activity and: lipid profile, Alzheimer's disease pathology, brain structure and brain function in healthy adults. Searches were carried out in PubMed, SCOPUS, Web of Science and PsycInfo.

Results

Thirty studies were included from 4,896 papers screened. Carriers of the e4 allele gained the same benefit from physical activity as non-carriers on most outcomes. For brain activation, e4 carriers appeared to gain a greater benefit from physical activity on task-related and resting-state activation and resting-state functional connectivity compared to non-carriers. Post-hoc analysis identified possible compensatory mechanisms allowing e4 carriers to maintain cognitive function.

Discussion

Though there is evidence suggesting physical activity may benefit e4 carriers differently compared to non-carriers, this may vary by the specific brain health outcome, perhaps limited to brain activation. Further research is required to confirm these findings and elucidate the mechanisms.

SUBMITTER: Pearce AM

PROVIDER: S-EPMC8833849 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Apolipoprotein E Genotype Moderation of the Association Between Physical Activity and Brain Health. A Systematic Review and Meta-Analysis.

Pearce Andrew M AM Marr Calum C Dewar Michaela M Gow Alan J AJ

Frontiers in aging neuroscience 20220128

<h4>Introduction</h4>Possession of one or two e4 alleles of the apolipoprotein E (<i>APOE</i>) gene is associated with cognitive decline and dementia risk. Some evidence suggests that physical activity may benefit carriers of the e4 allele differently.<h4>Method</h4>We conducted a systematic review and meta-analysis of studies which assessed <i>APOE</i> differences in the association between physical activity and: lipid profile, Alzheimer's disease pathology, brain structure and brain function i ...[more]

PMID: 35153725

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Project description:In addition to being the greatest genetic risk factor for Alzheimer's disease, expression of the ɛ4 allele of apolipoprotein E can lead to cognitive decline during ageing that is independent of Alzheimer's amyloid-β and tau pathology. In human post-mortem tissue and mouse models humanized for apolipoprotein E, we examined the impact of apolipoprotein E4 expression on brain exosomes, vesicles that are produced within and secreted from late-endocytic multivesicular bodies. Compared to humans or mice homozygous for the risk-neutral ɛ3 allele we show that the ɛ4 allele, whether homozygous or heterozygous with an ɛ3 allele, drives lower exosome levels in the brain extracellular space. In mice, we show that the apolipoprotein E4-driven change in brain exosome levels is age-dependent: while not present at age 6 months, it is detectable at 12 months of age. Expression levels of the exosome pathway regulators tumor susceptibility gene 101 (TSG101) and Ras-related protein Rab35 (RAB35) were found to be reduced in the brain at the protein and mRNA levels, arguing that apolipoprotein E4 genotype leads to a downregulation of exosome biosynthesis and release. Compromised exosome production is likely to have adverse effects, including diminishing a cell's ability to eliminate materials from the endosomal-lysosomal system. This reduction in brain exosome levels in 12-month-old apolipoprotein E4 mice occurs earlier than our previously reported brain endosomal pathway changes, arguing that an apolipoprotein E4-driven failure in exosome production plays a primary role in endosomal and lysosomal deficits that occur in apolipoprotein E4 mouse and human brains. Disruption of these interdependent endosomal-exosomal-lysosomal systems in apolipoprotein E4-expressing individuals may contribute to amyloidogenic amyloid-β precursor protein processing, compromise trophic signalling and synaptic function, and interfere with a neuron's ability to degrade material, all of which are events that lead to neuronal vulnerability and higher risk of Alzheimer's disease development. Together, these data suggest that exosome pathway dysfunction is a previously unappreciated component of the brain pathologies that occur as a result of apolipoprotein E4 expression.

Project description:BackgroundPhysical activity (PA) may protect against infertility by modulating the hypothalamic-pituitary-gonadal axis, thereby reducing gonadotropin levels, elevating immune function, and inhibiting inflammation and circulating sex hormones. However, whether PA reduces the risk of infertility remains largely unknown. We therefore conducted a systematic review and meta-analysis to determine the preventive effects of PA on infertility.MethodsWe searched PubMed, Cochrane Library, EMBASE, and CINAHL databases to retrieve published epidemiologic studies on the relationship between PA and infertility. Following the PRISMA guidelines, we selected English literature publishedprior to 11 April 2022, and assessed study quality using the Newcastle-Ottawa Scale. Our protocol, including the full methods employed for this review, is available on PROSPERO (ID = CRD42020143344).ResultsSix cohort studies and four case-control studies based on 708,965 subjects and 12,580 cases were eventually screened and retained. High levels of PA were shown to reduced risk of infertility relative to low levels (cumulative relative risk [RR] = 0.59, with a 95% confidence interval CI 0.49-0.71), and we reported results for cohort studies (RR = 0.63, 95% CI 0.50-0.79) and case-control studies (RR = 0.49, 95% CI 0.35-0.67). Our findings were comparable for men (RR = 0.65, 95% CI 0.41-1.04) and women (RR = 0.56, 95% CI 0.47-0.66). The meta-analysis of six risk estimates from five studies of low, moderate, and high PA levels showed that moderate PA may also reduce the risk of infertility compared with low PA (RR = 0.54, 95% CI 0.38-0.77). However, high PA also appeared to slightly augment the risk of infertility compared with moderate PA (RR = 1.31, 95% CI 1.08-1.59).ConclusionsThis present systematic review comprehensively reflected an inverse relationship between different levels of PA and infertility, and our meta-analysis showed that a moderate-to-high PA level significantly reduced the overall risk of infertility, and that this level of PA activity was a common protective factor. In addition, limited evidence suggested that compliance with international PA guidelines would greatly lower the risk of infertility (RR = 0.58, 95% CI 0.45-0.74; I2 = 0.0%). Future studies, however, need to be executed to further determine the frequency, optimal dosage, and duration required to effectively attenuate the risk of infertility.

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Project description:BackgroundPhysical activity may protect against bladder cancer through several biologic pathways, such as enhanced immune function and decreased chronic inflammation. Physical activity may also indirectly prevent bladder cancer by reducing obesity. A sizeable number of epidemiologic studies have examined the association between physical activity and bladder cancer, but the available evidence has not yet been formally summarised using meta-analysis.MethodsWe performed a systematic literature review and meta-analysis of English-language studies published from January 1975 through November 2013. We followed the PRISMA guidelines and used a random effects model to estimate the summary risk estimates for the association between physical activity and bladder cancer.ResultsA total of 15 studies with 5,402,369 subjects and 27,784 bladder cancer cases were included. High vs low levels of physical activity were related to decreased bladder cancer risk (summary relative risk (RR)=0.85, 95% confidence interval (CI)=0.74-0.98; I(2)=83%; P-value for heterogeneity across all studies<0.001). Results were similar for cohort studies (RR=0.89, 95% CI=0.80-1.00; I(2)=64%) and case-control studies (RR=0.71, 95% CI=0.43-1.16; I(2)=87%; P-value for difference=0.108) and they were comparable for women (RR=0.83, 95% CI=0.73-0.94; I(2)=0%) and men (RR=0.92, 95% CI=0.82-1.05; I(2)=67; P-value for difference=0.657). Findings were also comparable for recreational (RR=0.81, 95% CI=0.66-0.99; I(2)=77%) and occupational physical activity (RR=0.90, 95% CI=0.76-1.0; I(2)=76%; P-value for difference=0.374), and they were largely consistent for moderate (RR=0.85, 95% CI=0.75-0.98; I(2)=76%) and vigorous activity (RR=0.80, 95% CI=0.64-1.00;I(2)=87%; P-value for difference=0.535).ConclusionsPhysical activity is associated with decreased risk of bladder cancer. Further studies are required to assess the relations of intensity, frequency, duration, and timing in life of physical activity to bladder cancer risk.

Dataset Information

Apolipoprotein E Genotype Moderation of the Association Between Physical Activity and Brain Health. A Systematic Review and Meta-Analysis.

Introduction

Method

Results

Discussion

Publications

Apolipoprotein E Genotype Moderation of the Association Between Physical Activity and Brain Health. A Systematic Review and Meta-Analysis.

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