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Journal of Alzheimer's Disease : JAD 2021The global race-dependent association of Alzheimer's disease (AD) and apolipoprotein E (APOE) genotype is not well understood. Transethnic analysis of APOE could clarify... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The global race-dependent association of Alzheimer's disease (AD) and apolipoprotein E (APOE) genotype is not well understood. Transethnic analysis of APOE could clarify the role of genetics in AD risk across populations.
OBJECTIVE
This study aims to determine how race and APOE genotype affect the risks for AD.
METHODS
We performed a systematic search of PubMed, Embase, Web of Science, and the Cochrane Library since 1993 to Aug 25, 2020. A total of 10,395 reports were identified, and 133 were eligible for analysis with data on 77,402 participants. Studies contained AD clinical diagnostic and APOE genotype data. Homogeneous data sets were pooled in case-control analyses. Odds ratios and 95% confidence intervals for developing AD were calculated for populations of different races and APOE genotypes.
RESULTS
The proportion of APOE genotypes and alleles differed between populations of different races. Results showed that APOEɛ4 was a risk factor for AD, whereas APOEɛ2 protected against it. The effects of APOEɛ4 and ɛ2 on AD risk were distinct in various races, and they were substantially attenuated among Black people. Sub-group analysis found a higher frequency of APOEɛ4/ɛ4 and lower frequency of APOEɛ3/ɛ3 among early-onset AD than late-onset AD in a combined group and different races.
CONCLUSION
Our meta-analysis suggests that the association of APOE genotypes and AD differ among races. These results enhance our understanding of APOE-related risk for AD across race backgrounds and provide new insights into precision medicine for AD.
Topics: Alleles; Alzheimer Disease; Apolipoprotein E2; Apolipoprotein E4; Apolipoproteins E; Genotype; Humans; Racial Groups
PubMed: 34334408
DOI: 10.3233/JAD-210549 -
Cureus Dec 2020Alzheimer's disease (AD) is caused by several risk factors leading to dementia. It's diagnosis usually depends on clinical presentation and certain biomarkers in the... (Review)
Review
Alzheimer's disease (AD) is caused by several risk factors leading to dementia. It's diagnosis usually depends on clinical presentation and certain biomarkers in the cerebrospinal fluid (CSF). The brain has a high content of cholesterol and the metabolism of cholesterol in the brain can be associated with beta-amyloid plaques formation, which is seen in Alzheimer's disease. Given these implications, we studied if plasma lipid levels can vary in Alzheimer's disease and if these can be used as biomarkers to diagnose and predict the progression of Alzheimer's disease. Certain mutations in the brain cholesterol transport receptors and proteins and their association with Alzheimer's were also studied. This systematic review abides by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched multiple databases, such as Pubmed, Google Scholar, Pubmed central, ScienceDirect, Web of Science, and Medline with the help of keywords like Alzheimer's disease, cognitive impairment, plasma lipid biomarkers, cholesterol, brain cholesterol metabolism separately and in combination with each other. We collected 49 quality appraised articles on the association between plasma lipids and Alzheimer's disease and the genetic mutations in alleles related to cholesterol metabolism and Alzheimer's disease by applying the inclusion and exclusion criteria. Based on the finding of the studies reviewed, we found an association between plasma lipids, polymorphisms in genes associated with cholesterol transport, and Alzheimer's disease. Increased serum low-density lipoprotein (LDL-C), triglycerides (TG), total cholesterol (TC), sphingolipids, 24S hydroxycholesterol (24S-HC), 27O hydroxycholesterol (27O-HC) was associated with Alzheimer's. Decreased high-density lipoprotein (HDL-C) and phospholipids were noticed. Genetic mutations in apolipoprotein E (ApoE), apolipoprotein B (ApoB), apolipoprotein A (ApoA), ATP binding cassette transporter 1 (ABCA1), ATP binding cassette transporter 7 (ABCA7), amyloid precursor protein (APP), cytochrome P450 family 46 subfamilies A member 1 (CYP46A1), presenilin 1 (PSEN1), presenilin 2 (PSEN2) are also associated with increased risk of Alzheimer's disease. This study found an association between plasma lipids and Alzheimer's, proving that plasma lipids can be used as biomarkers for early diagnosis of Alzheimer's disease. It may also help predict the prognosis and stage the disease severity. Further studies are needed to find out the exact mechanism behind these changes.
PubMed: 33457117
DOI: 10.7759/cureus.12008 -
Schizophrenia Research Dec 2015Schizophrenia affects between 0.3% and 2% of the worldwide population. A genetic contribution has been postulated in the development of this disorder. Genes such as ApoE... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Schizophrenia affects between 0.3% and 2% of the worldwide population. A genetic contribution has been postulated in the development of this disorder. Genes such as ApoE have been implicated in the neurodevelopment associated with schizophrenia in case-control and meta-analysis studies, but the results remain inconclusive. Due to this, the aim of the present study was to explore the association between ApoE and schizophrenia through a meta-analysis.
MATERIAL AND METHODS
We collected all relevant studies by searching PubMed and EBSCO databases. The pooled odds ratios with 95% confidence intervals were calculated to estimate the association. The following models were evaluated: A) ε4 vs ε3, B) ε4 vs ε2, C) ε4 vs ε3+ε2, D) Caucasian population and E) Asian population. Statistical analyses were performed using EPIDAT 3.1 software.
RESULTS
The meta-analyses comprised 28 association studies, which included 4703 controls and 3452 subjects with schizophrenia. A significant protective effect was found for allele ε3 in the Asian population (OR=0.73, 95% CI=0.54-0.98). No significant associations were observed in the other models and populations analyzed.
CONCLUSIONS
Our meta-analysis suggests a protective association between ApoE allele ε3 and schizophrenia in the Asian population.
Topics: Apolipoproteins E; Databases, Bibliographic; Humans; Schizophrenia
PubMed: 26372448
DOI: 10.1016/j.schres.2015.08.031 -
Frontiers in Cardiovascular Medicine 2023Carotid atherosclerotic plaque is an important independent risk factor for stroke. Apolipoprotein E (APOE) influences cholesterol levels and certain isoforms are...
INTRODUCTION
Carotid atherosclerotic plaque is an important independent risk factor for stroke. Apolipoprotein E (APOE) influences cholesterol levels and certain isoforms are associated with increased carotid atherosclerosis, though the exact association between APOE and carotid plaque is uncertain. The study aimed to evaluate the association between APOE and carotid plaque.
METHODS
A systematic review was performed to retrieve all studies which examined the association between carotid plaque and APOE. This study was conducted in accordance with the PRISMA guidelines. Independent readers extracted the relevant data from each study including the type of imaging assessment, plaque definition, frequency of APOE E4 carrier status and type of genotyping. Meta-analyses with an assessment of study heterogeneity and publication bias were performed. Results were presented in a forest plot and summarized using a random-effects model.
RESULTS
After screening 838 studies, 17 studies were included for systematic review. A meta-analysis of 5 published studies showed a significant association between 4 homozygosity and carotid plaque [odds ratio (OR), 1.53; 95% CI, 1.16, 2.02; = .003]. Additionally, there was a significant association between patients possessing at least one 4 allele, heterozygotes or homozygotes, and carotid plaque (OR, 1.25; 95% CI, 1.03, 1.52; = .03). Lastly, there was no association between 4 heterozygosity and carotid plaque (OR, 1.08; 95% CI, 0.93, 1.26; = .30).
CONCLUSION
APOE 4 allele is significantly associated with extracranial carotid atherosclerotic plaque, especially for homozygous individuals.
PubMed: 38034385
DOI: 10.3389/fcvm.2023.1155916 -
PloS One 2014To investigate the relationship of Apolipoprotein E (APOE) gene polymorphism to colorectal neoplasia (CRN), we performed a systematic review and meta-analysis. Eligible... (Meta-Analysis)
Meta-Analysis
To investigate the relationship of Apolipoprotein E (APOE) gene polymorphism to colorectal neoplasia (CRN), we performed a systematic review and meta-analysis. Eligible studies were identified through a systematic literature review from PubMed, EMBASE, and the Science Citation Index up to February 2014. A combined analysis was performed, followed by a subgroup analyses stratified by the study design. We used data collected from 8 prospective studies involving respectively a total of 9243 participants and 4310 CRN cases which including 438 patients with colorectal adenoma (CRA), and 3873 patients with colorectal carcinoma (CRC). The pooled data from this meta-analysis indicated there was no significant association between APOE polymorphism and CRN (ε2: P = 0.51, OR 1.04 95% CI 0.93 to 1.16; ε4: P = 0.72, OR 0.98 95% CI 0.90 to 1.07). Interestingly, subgroup analysis demonstrated there was a significant decreased risk for proximal CRN in patients with APOE ε4 (P = 0.0007, OR 0.52 95% CI 0.35 to 0.76). Data showed no significant association between APOE genotype and overall CRN. However, compared with those carry APOE ε3 alleles, persons with APOE ε4 genotype have significant decreased risk suffering from proximal CRN but not from distal CRN.
Topics: Apolipoproteins E; Colorectal Neoplasms; Gene Frequency; Genotype; Humans; Odds Ratio; Polymorphism, Genetic
PubMed: 25029444
DOI: 10.1371/journal.pone.0102477 -
Journal of Hypertension Jun 2016Diuretic drugs have been a mainstay of hypertension treatment in the elderly however their dementia sparing effects are under-reported. The objective was to quantify... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Diuretic drugs have been a mainstay of hypertension treatment in the elderly however their dementia sparing effects are under-reported. The objective was to quantify dementia risk in relation to diuretic antihypertensive drugs.
METHODS
Electronic databases were searched until June 2015.
ELIGIBILITY CRITERIA
population, adults without dementia from primary care, community cohort, residential/institutionalized, or randomized controlled trial; exposure, diuretic antihypertensive drug; comparison, no diuretic drug, other or no antihypertensive drug, placebo-control; outcome, incident dementia diagnosed by standardized criteria. Adjusted hazard ratios (HR) with 95% confidence intervals (CI) were pooled in fixed-effects models with RevMan 5.3 (The Nordic Cochrane Centre, Copenhagen, Denmark) and the findings rated according to The Grading of Recommendations Assessment, Development and Evaluation criteria.
RESULTS
A total of 15 articles were included (52 599 persons, 3444 dementia cases, median age 76.1 years) and median follow-up was 6.1 years. Diuretics were associated with reduced dementia risk (HR 0.83; 95% CI 0.76-0.91, P < 0.0001, I = 0) and Alzheimer's disease risk (HR 0.82; 95% CI 0.71-0.94, P = 0.004, I = 0). Stratified analysis indicated a difference between potassium sparing, thiazide and loop diuretics (P = 0.01). Risk estimates were generally consistent comparing monotherapy vs. combination therapy, study design and follow-up. Meta-regression showed that demographics, stroke, heart failure, diabetes, liver disease, attrition, mortality rate, cognitive function, and apolipoprotein E allele did not moderate the results.
CONCLUSION
Diuretic antihypertensive drugs were associated with a consistent reduction in dementia risk without heterogeneity, pointing to generalizability of these findings.
REGISTRATION
PROSPERO [CRD42015023428].
Topics: Alzheimer Disease; Antihypertensive Agents; Dementia; Diuretics; Diuretics, Potassium Sparing; Drug Therapy, Combination; Humans; Hypertension; Prospective Studies; Protective Factors; Sodium Potassium Chloride Symporter Inhibitors
PubMed: 26886565
DOI: 10.1097/HJH.0000000000000868 -
The Journal of Gene Medicine Mar 2023In order to clarify the role of the maternal apolipoprotein E (ApoE) genotype and the risk of recurrent pregnancy loss (RPL), we herein performed an updated systematic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In order to clarify the role of the maternal apolipoprotein E (ApoE) genotype and the risk of recurrent pregnancy loss (RPL), we herein performed an updated systematic review and meta-analysis to reevaluate the evidence on this association.
METHODS
A comprehensive literature search was performed on PubMed, Web of Knowledge and the Cochrane library up to September 2022. Methodological study quality was assessed using the Newcastle-Ottawa Scale and the credibility of significant pooled odds ratios (ORs) was estimated by the false positive report probability and the Bayesian false discovery probability.
RESULTS
Twelve studies published from 2009 to 2022 fulfilled the inclusion criteria. In the overall analysis, the ε4 allele was found to confer an increased risk of RPL compared to the ε3 allele (OR 1.60, 95% CI 1.00-2.55, p = 0.049) and women carrying the ApoE ε4 allele displayed a higher risk of RPL compared with those carrying the ε2 and ε3 alleles (OR 1.75, 95% CI 1.06-2.87, p = 0.028). Subgroup analysis based on subjects' ethnicity revealed that these associations were restricted to the Asian population (ε4 allele vs. ε3 allele, OR 5.93, 95% CI 1.79-19.61, p = 0.004; ε4 allele carriers vs. carriers of ε2 and ε3 alleles, OR 8.42, 95% CI 1.47-48.12, p = 0.017). None of the associations detected were found to be noteworthy under false positive report probability or Bayesian false discovery probability at a prior probability of 0.001.
CONCLUSIONS
This updated meta-analysis highlights an association between maternal ApoE genotype and RPL risk in Asians, but not in Caucasians. Further case-control studies are warranted in women of Asian ancestry to exclude the possibility of false-positive findings.
Topics: Female; Humans; Abortion, Habitual; Apolipoproteins E; Bayes Theorem; Genotype; Heterozygote
PubMed: 36479790
DOI: 10.1002/jgm.3467 -
BJPsych Open Oct 2023Studies have shown a relationship between oestrogen and Alzheimer's disease. However, there is neither clear nor strong evidence on the use of oestrogen-only therapy in... (Review)
Review
BACKGROUND
Studies have shown a relationship between oestrogen and Alzheimer's disease. However, there is neither clear nor strong evidence on the use of oestrogen-only therapy in reducing the risk of Alzheimer's disease.
AIMS
To assess the effects of oestrogen-only therapy on reducing the risk of Alzheimer's disease.
METHOD
Inclusion criteria was determined with the PICO framework. Outcome was cognitive function measured by neuropsychological tests and strict protocols. Exclusion criteria included non-Alzheimer's dementia, progesterone-only therapy and pre-menopausal women. Searches were conducted in nine electronic healthcare databases, last searched in July 2022. Quality assessments conducted on randomised controlled trials (RCTs) were performed with the GRADE assessment, and cohort studies and case-control studies were assessed with the Newcastle-Ottawa Scale. Extracted data were used to analyse participants, interventions and outcomes.
RESULTS
Twenty-four studies satisfied the search criteria (four RCTs, nine cohort studies, 11 case-control studies). Fifteen studies showed positive associations for oestrogen-only therapy reducing the risk of Alzheimer's disease, and the remaining nine found no evidence of association.
CONCLUSIONS
Fifteen studies showed that oestrogen-only therapy effectively reduced the risk of Alzheimer's disease, whereas nine showed no correlation. Studies also investigated oestrogen-related variables such as length of oestrogen exposure, being an apolipoprotein E ε4 carrier and concomitant use of non-steroidal anti-inflammatory drugs, and their role in neuroprotection. This review was limited by the limited ranges of duration of oestrogen treatment and type of oestrogen-only therapy used. In conclusion, oestrogen-only therapy has potential for use in preventing Alzheimer's disease, although current evidence is inconclusive and requires further study.
PubMed: 37846476
DOI: 10.1192/bjo.2023.579 -
NeuroImage. Clinical 2020Diffusion magnetic resonance imaging (dMRI) is an imaging technique which probes the random motion of water molecules in tissues and has been widely applied to... (Review)
Review
Diffusion magnetic resonance imaging (dMRI) is an imaging technique which probes the random motion of water molecules in tissues and has been widely applied to investigate changes in white matter microstructure in Alzheimer's Disease. This paper aims to systematically review studies that examined the effect of Alzheimer's risk genes on white matter microstructure. We assimilated findings from 37 studies and reviewed their diffusion pre-processing and analysis methods. Most studies estimate the diffusion tensor (DT) and compare derived quantitative measures such as fractional anisotropy and mean diffusivity between groups. Those with increased AD genetic risk are associated with reduced anisotropy and increased diffusivity across the brain, most notably the temporal and frontal lobes, cingulum and corpus callosum. Structural abnormalities are most evident amongst those with established Alzheimer's Disease. Recent studies employ signal representations and analysis frameworks beyond DT MRI but show that dMRI overall lacks specificity to disease pathology. However, as the field advances, these techniques may prove useful in pre-symptomatic diagnosis or staging of Alzheimer's disease.
Topics: Alzheimer Disease; Anisotropy; Brain; Diffusion Magnetic Resonance Imaging; Diffusion Tensor Imaging; Humans; White Matter
PubMed: 32758801
DOI: 10.1016/j.nicl.2020.102359 -
Brain Injury 2015The apolipoprotein E gene (APOE) has emerged as a candidate for prognosticating traumatic brain injury (TBI) recovery, with APOEε4 identified as a susceptibility marker... (Review)
Review
BACKGROUND
The apolipoprotein E gene (APOE) has emerged as a candidate for prognosticating traumatic brain injury (TBI) recovery, with APOEε4 identified as a susceptibility marker for poor outcome, despite large discrepancy in its reported influence post-TBI.
METHODS
A systematic review was conducted, including all primary articles investigating the role of APOEε4 on TBI outcome. A total of 65 studies were included, including 24 predominantly investigating mild (mTBI), seven moderate (modTBI) and 33 severe (sTBI); severity was not reported in one study.
RESULTS
In mTBI studies, the association between APOEε4 and post-TBI outcome was concluded as non-contributory in 14 studies (58.3%), hazardous in nine (37.5%) and protective in one (4.2%). In sTBI studies, the role of APOEε4 was hazardous in 21 (63.6%), non-contributory in nine (27.3%) and protective in three (9.1%). Of the seven studies investigating dementia outcomes, four observed a hazardous association with APOEε4, while three reported no association. Six studies examined Alzheimer's dementia pathology, of which three reported a hazardous influence of APOEε4.
CONCLUSIONS
The influence of APOEε4 on neuropsychological testing, functional outcome and in paediatric populations was incongruous. This review supports the majority of research indicating APOEε4 adversely influences recovery following TBI, particularly with respect to dementia-related outcomes and outcomes following sTBI.
Topics: Aged; Aged, 80 and over; Alleles; Apolipoprotein E4; Brain Injuries; Female; Genotype; Humans; Male; Prognosis; Treatment Outcome
PubMed: 25915580
DOI: 10.3109/02699052.2015.1005131