Can Physical Activity Reduce the Risk of Cognitive Decline in Apolipoprotein e4 Carriers? A Systematic Review.
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SUBMITTER: Perez-Lasierra JL
PROVIDER: S-EPMC8303365 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ImportancePhysical activity is associated with the risk for cognitive decline, but much of the evidence in this domain comes from studies with short follow-ups, which is prone to reverse causation bias.ObjectiveTo examine how length of follow-up, baseline age, physical activity amount, and study quality modify the longitudinal associations of physical activity with cognition.Data sourcesObservational studies of adults with a prospective follow-up of at least 1 year, a valid baseline cognitive measure or midlife cohort, and an estimate of the association of baseline physical activity and follow-up cognition were sought from PsycInfo, Scopus, CINAHL, Web of Science, SPORTDiscus, and PubMed, with the final search conducted on November 2, 2022.Study selectionTwo independent researchers screened titles with abstracts and full-text reports.Data extraction and synthesisTwo reviewers independently assessed study quality and extracted data. Pooled estimates of association were calculated with random-effects meta-analyses. An extensive set of moderators, funnel plots, and scatter plots of physical activity amount were examined. This study is reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.Main outcomes and measuresPooled estimates of the associations between physical activity and global cognition, as well as specific cognitive domains, were examined.ResultsA total of 104 studies with 341 471 participants were assessed. Analysis of binary outcomes included 45 studies with 102 452 individuals, analysis of follow-up global cognition included 14 studies with 41 045 individuals, and analysis of change in global cognition included 25 studies with 67 463 individuals. Physical activity was associated with a decreased incidence of cognitive impairment or decline after correction for funnel plot asymmetry (pooled risk ratio, 0.97; 95% CI, 0.97-0.99), but there was no significant association in follow-ups longer than 10 years. Physical activity was associated with follow-up global cognition (standardized regression coefficient, 0.03; 95% CI, 0.02-0.03) and change in global cognition (standardized regression coefficient, 0.01; 95% CI, 0.01 to 0.02) from trim-and-fill analyses, with no clear dose-response or moderation by follow-up length, baseline age, study quality or adjustment for baseline cognition. The specific cognitive domains associated with physical activity were episodic memory (standardized regression coefficient, 0.03; 95% CI, 0.02-0.04) and verbal fluency (standardized regression coefficient, 0.05; 95% CI, 0.03-0.08).Conclusions and relevanceIn this meta-analysis of the association of physical activity with cognitive decline, physical activity was associated with better late-life cognition, but the association was weak. However, even a weak association is important from a population health perspective.
| S-EPMC10835510 | biostudies-literature
Project description:Current treatment in late-life cognitive impairment and dementia is still limited, and there is no cure for brain tissue degeneration or reversal of cognitive decline. Physical activity represents a promising non-pharmacological interventional approach in many diseases causing cognitive impairment, but its effect on brain integrity is still largely unknown. Especially research of cerebral alterations in disease state that goes beyond observations of clinical improvement is crucial to understand disease processes and possible effective treatments. In this systematic review, we address the question how physical activity and fitness in mild cognitive impairment (MCI) and Alzheimer's disease (AD) influences brain architecture compared to cognitively healthy elderly. We review both interventional studies comprising aerobic, coordinative and resistance exercises and observational studies on fitness and physical activity combined with Magnetic Resonance imaging (MRI). Different MRI approaches were included such as volumetric and structural analyses, Diffusion Tensor Imaging (DTI), functional MRI and Cerebral Blood Flow (CBF). We evaluate MRI results for different exercise modalities and performed a methodological evaluation of interventional studies in cognitive decline compared to normal aging. According to our results, among 12 interventions in AD/MCI, aerobic exercise is most frequently applied (9 studies). Interventions in AD/MCI altogether reveal a higher methodological quality compared to interventions in healthy elderly (8.33 ± 2.19 vs. 6.25 ± 2.36 out of 13 points), with most frequent missing aspects related to descriptions of complications, lack of intention-to-treat and statistical power analyses. Effects of aerobic exercise and fitness seem to mainly impact brain structures sensitive to neurodegeneration, which especially comprise frontal, temporal and parietal regions, such as the hippocampal/parahippocampal region, precuneus, anterior cingulate and prefrontal cortex, which are reported by several studies. General fitness measured via an objective fitness assessment and questionnaires seems to have a more global cerebral effect, probably due to its long-term application, whereas distinct intervention effects of durations between 3 and 6 months seem to concentrate on more local brain regions as the hippocampus, which can also be influenced by region of interest analyses. There is still a lack of evidence on other or combined types of intervention modalities, such as resistance, coordinative as well as multicomponent exercise during cognitive decline, and complex interventions as dancing. Future research should examine their beneficial effect on brain integrity, since several non-MRI studies already point to their advantageous impact. As a further future prospect, combination and application of newly developed imaging methods such as metabolic imaging should be envisaged to understand physical activity and its cerebral influence under its many-sided facets.
| S-EPMC6699421 | biostudies-literature
Project description:BACKGROUND: Apolipoprotein E (APOE) polymorphisms are unequivocally associated with risk for Alzheimer's disease (AD). It is crucial to understand how this genetic factor affects dementia risk in the general population, as well as in narrowly diagnosed, selected, patient groups. METHODS: We assessed the cross sectional association between APOE genotype and dementia status in a community based sample, the MRC Cognitive Function and Ageing Study (MRC CFAS). In addition, we tested the effects of APOE genotypes on the differences in MMSE scores between the first and third assessment waves (about six years apart), an index of cognitive decline. RESULTS: The APOE epsilon4 allele conferred increased risk for dementia (OR=1.5, 95% CI=1.1 to 2.2) compared to epsilon3 in the MRC CFAS sample. Compared with APOE epsilon3/epsilon 3 subjects, those with the epsilon3/epsilon4 genotypes were not at significantly higher risk for dementia (OR=1.1, 95% CI=0.6 to 1.9), although epsilon4/epsilon4 subjects were (OR= 3.8, 95% CI=1.0 to 14.0). Risk estimates were not different between men and women. Notably, our risk estimates for dementia were significantly lower than those reported for a diagnosis of Alzheimer's disease. MMSE scores at wave 3 and the difference in MMSE between baseline and at the third assessment wave were not different across APOE genotypes. INTERPRETATION: The APOE epsilon4 allele is a weaker predictor for dementia in the general population than for AD. This may be because dementia can be caused by non-AD pathological processes and because most prevalent dementia occurs at an age when the APOE epsilon4 effect on AD risk (and therefore dementia) has started to decline.
| S-EPMC1735244 | biostudies-other
Project description:BackgroundBlood pressure variability (BPV) is associated with cognitive decline and Alzheimer's disease (AD), but relationships with AD risk gene apolipoprotein (APOE) ɛ4 remain understudied.ObjectiveExamined the longitudinal relationship between BPV and cognitive change in APOE ɛ4 carriers and APOE ɛ3 homozygotes.Methods1,194 Alzheimer's Disease Neuroimaging Initiative participants (554 APOE ɛ4 carriers) underwent 3-4 blood pressure measurements between study baseline and 12-month follow-up. Visit-to-visit BPV was calculated as variability independent of mean over these 12 months. Participants subsequently underwent ≥1 neuropsychological exam at 12-month follow-up or later (up to 156 months later). Composite scores for the domains of memory, language, executive function, and visuospatial abilities were determined. Linear mixed models examined the 3-way interaction of BPV×APOE ɛ4 carrier status x time predicting change in composite scores.ResultsHigher systolic BPV predicted greater decline in memory (+1 SD increase of BPV: β= -0.001, p < 0.001) and language (β= -0.002, p < 0.0001) among APOE ɛ4 carriers, but not APOE ɛ3 homozygotes (memory: +1 SD increase of BPV: β= 0.0001, p = 0.57; language: β= 0.0001, p = 0.72). Systolic BPV was not significantly associated with change in executive function or visuospatial abilities in APOE ɛ4 carriers (ps = 0.08-0.16) or APOE ɛ3 homozygotes (ps = 0.48-0.12).ConclusionCognitive decline associated with high BPV may be specifically accelerated among APOE ɛ4 carriers.
| S-EPMC10852980 | biostudies-literature
Project description:Cerebrovascular dysfunction likely contributes causally to Alzheimer's disease (AD). The strongest genetic risk factor for late-onset AD, Apolipoprotein E4 (APOE4), may act synergistically with vascular risk to cause dementia. Therefore, interventions that improve vascular health, such as exercise, may be particularly beneficial for APOE4 carriers. We assigned cognitively normal adults (65-87 years) to an aerobic exercise intervention or education only. Arterial spin labeling MRI measured hippocampal blood flow (HBF) before and after the 52-week intervention. We selected participants with hypertension at enrollment (n = 44). For APOE4 carriers, change in HBF (ΔHBF) was significantly (p = 0.006) higher for participants in the exercise intervention (4.09 mL/100g/min) than the control group (-2.08 mL/100g/min). There was no difference in ΔHBF between the control (-0.32 mL/100g/min) and exercise (-0.54 mL/100g/min) groups for non-carriers (p = 0.918). Additionally, a multiple regression showed an interaction between change in systolic blood pressure (ΔSBP) and APOE4 carrier status on ΔHBF (p = 0.035), with reductions in SBP increasing HBF for APOE4 carriers only. Aerobic exercise improved HBF for hypertensive APOE4 carriers only. Additionally, only APOE4 carriers exhibited an inverse relationship between ΔSBP and ΔHBF. This suggests exercise interventions, particularly those that lower SBP, may be beneficial for individuals at highest genetic risk of AD.ClinicalTrials.gov Identifier: NCT02000583.
| S-EPMC8327103 | biostudies-literature
Project description:Recent evidence suggests that a high glycemic load (GL) diet is a risk factor for dementia, especially among apolipoprotein E ε4 allele (APOE4) carriers, while its association with cognitive decline is poorly known. Here, we investigated the association of high-GL meals with cognitive decline in older adults during a 12-year follow-up, according to their APOE4 carrier status. We used random-effect models and data from 2539 elderly participants from the Three-City study who completed a food frequency questionnaire (FFQ) to longitudinally assess the association of GL with changes in different cognitive domains (verbal fluency, visual memory, attention, visual motor processing speed, episodic memory). In APOE4 carriers, afternoon snack with high GL was significantly associated with cognitive decline in visual memory, episodic memory, and global cognition compared with APOE4 non-carriers. This study suggests a detrimental association between a high-GL diet and cognitive decline. The promotion of a low GL diet as a target to prevent cognitive decline in high-risk populations deserves more research.
| S-EPMC7761247 | biostudies-literature
Project description:BackgroundBy 2050, it has been estimated that approximately one-fifth of the population will be made up of older adults (aged ≥60 years). Old age often comes with cognitive decline and dementia. Physical activity may prevent cognitive decline and dementia.MethodsWe reviewed and synthesised prospective studies into physical activity and cognitive decline, and physical activity and dementia, published until January 2014. Forty-seven cohorts, derived from two previous systematic reviews and an updated database search, were used in the meta-analyses. Included participants were aged ≥40 years, in good health and/or randomly selected from the community. Studies were assessed for methodological quality.ResultsTwenty-one cohorts on physical activity and cognitive decline and twenty-six cohorts on physical activity and dementia were included. Meta-analysis, using the quality-effects model, suggests that participants with higher levels of physical activity, when compared to those with lower levels, are at reduced risk of cognitive decline, RR 0.65, 95% CI 0.55-0.76, and dementia, RR 0.86, 95% CI 0.76-0.97. Sensitivity analyses revealed a more conservative estimate of the impact of physical activity on cognitive decline and dementia for high quality studies, studies reporting effect sizes as ORs, greater number of adjustments (≥10), and longer follow-up time (≥10 years). When one heavily weighted study was excluded, physical activity was associated with an 18% reduction in the risk of dementia (RR 0.82; 0.73-0.91).ConclusionsLongitudinal observational studies show an association between higher levels of physical activity and a reduced risk of cognitive decline and dementia. A case can be made for a causal interpretation. Future research should use objective measures of physical activity, adjust for the full range of confounders and have adequate follow-up length. Ideally, randomised controlled trials will be conducted. Regardless of any effect on cognition, physical activity should be encouraged, as it has been shown to be beneficial on numerous levels.
| S-EPMC4064273 | biostudies-literature
Project description:BackgroundAlthough increasing physical activity (PA) has been suggested to prevent and manage cognitive decline and dementia, its economic impact on healthcare systems and society is largely unknown. This study aimed to summarize evidence on the cost-effectiveness of PA interventions to prevent and manage cognitive decline and dementia.MethodsElectronic databases, including PubMed/MEDLINE, Embase, and ScienceDirect, were searched from January 2000 to July 2023. The search strategy was driven by a combination of subject-heading terms related to physical activity, cognitive function, dementia, and cost-effectiveness. Selected studies were included in narrative synthesis, and extracted data were presented in narrative and tabular forms. The risk of bias in each study was assessed using the Consolidated Health Economic Evaluation Reporting Standards and Consensus on Health Economic Criteria list.ResultsFive of the 11 identified studies focused on individuals with existing dementia. Six of the 11 identified studies focused on individuals with no existing dementia, including 3 on those with mild cognitive impairment (MCI), and 3 on those with no existing MCI or dementia. PA interventions focused on individuals with no existing dementia were found to be cost-effective compared to the control group. Findings were mixed for PA interventions implemented in individuals with existing dementia.ConclusionsPA interventions implemented before or during the early stage of cognitive impairment may be cost-effective in reducing the burden of dementia. More research is needed to investigate the cost-effectiveness of PA interventions in managing dementia. Most existing studies used short-term outcomes in evaluating the cost-effectiveness of PA interventions in the prevention and management of dementia; future research should consider adding long-term outcomes to strengthen the study design.
| S-EPMC10519096 | biostudies-literature
Project description:BackgroundThe apolipoprotein E (APOE) e4 allele is a well-established genetic risk factor of brain aging. Vigorous physical activity may be particularly important in APOE-e4 carriers, but data have been inconsistent, likely due to differences in the timing of the physical activity assessment, definition of cognitive decline, and/or sample size.MethodsWe prospectively evaluated the association between vigorous physical activity and cognition assessed at least 9 years later, according to APOE-e4 carrier status. Biennially from 1986, Nurses' Health Study participants reported their leisure-time physical activities. Starting in 1995-2001 and through 2008, participants (aged 70+ years) underwent up to 4 repeated cognitive telephone assessments (6 tasks averaged together using z-scores).ResultsAmong 7252 women, latent process mixed models identified 3 major patterns of cognitive change over 6 years: high-stable, medium-stable, and decline. Taking the high-stable cognitive trajectory as the outcome reference in multinomial logistic regressions, highest tertile of vigorous physical activity (≥5.9 metabolic-equivalent [MET]-hours/wk) compared to lowest tertile (≤0.9 MET-hours/wk) was significantly associated with subsequent lower likelihood of the medium-stable trajectory in the global score (odds ratio [OR] [95% CI] = 0.72 [0.63, 0.82]), verbal memory (OR [95% CI] = 0.78 [0.68-0.89]), and telephone interview of cognitive status score (OR [95% CI] = 0.81 [0.70-0.94]). Vigorous physical activity was also associated with lower likelihood of decline in category fluency (OR [95% CI] = 0.72 [0.56, 0.92]). We observed some evidence (p-interaction = .07 for the global score) that the association was stronger among APOE-e4 carriers than noncarriers (OR [95% CI] = 0.60 [0.39, 0.92] vs 0.82 [0.59, 1.16]).ConclusionMidlife vigorous physical activity was associated with better cognitive trajectories in women in their seventies, with suggestions of stronger associations among APOE-e4 carriers.
| S-EPMC8974346 | biostudies-literature
Project description:BACKGROUND:Apolipoprotein E4 (apoE4), the major genetic risk factor for Alzheimer's disease (AD) and other neurodegenerative diseases, has three structural and biophysical properties that distinguish it from the other isoforms-domain interaction, reduced stability, and lack of cysteine. Assessing their relative contributions to effects of apoE4-associated pathogenesis in AD is important from a mechanistic and therapeutic perspective, that is not possible using human apoE transgene or knock-in models. METHODS:We analyzed Arg-61 apoE mice, a gene-targeted model that selectively displays domain interaction. RESULTS:The mice displayed age-dependent loss of the synaptic protein synaptophysin in neocortex and hippocampus and had lower levels of the postsynaptic neuroligin-1. Activation of dentate gyrus granule neurons increased Arc expression 3.5-fold in wildtype mice but only 2.3-fold in Arg-61 mice. The losses of synaptic proteins caused a mild memory deficit in Arg-61 mice in the water-maze test. Since synaptic integrity requires efficient glutamate uptake, we measured astrocyte glutamate transporter 1 in the hippocampus. The level was reduced in Arg-61 mice, suggesting that inefficient glutamate uptake by astrocytes causes chronic excitotoxicity. Consistent with the reduced secretion of Arg-61 apoE by astrocytes in this model, cholesterol secretion was also reduced 34%. This reduction could also contribute to the synaptic deficits by limiting the availability of cholesterol for neuronal repair. CONCLUSIONS:Domain interaction in the absence of other structural characteristics of apoE4 is sufficient to cause synaptic pathology and functional synaptic deficits, potentially associated with astrocyte dysfunction and impaired maintenance of neurons. Therapeutic targeting of domain interaction might blunt effects of apoE4 in neurodegenerative disease.
| S-EPMC2647370 | biostudies-literature