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Frontiers in Neuroanatomy 2024Literature suggests a common pathophysiological ground between carotid atherosclerosis (CAS) and white matter alterations in the brain. However, the association between...
INTRODUCTION
Literature suggests a common pathophysiological ground between carotid atherosclerosis (CAS) and white matter alterations in the brain. However, the association between carotid intima-media thickness (CIMT) and white matter hyperintensities (WMH) has not been conclusively reported. The current systematic review explores and reports the relationship between CIMT and WMH among asymptomatic/non-stroke adults.
METHODS
A recent literature search on PubMed, SCOPUS, and Web of Science databases was conducted in compliance with the PRISMA protocol. The pre-defined Population-Intervention-Comparison-Outcome-Study (PICOS) criteria included observational studies investigating the CIMT-WMH association among non-stroke adults undergoing magnetic resonance imaging and carotid ultrasound.
RESULTS
Out of 255 potential results, 32 studies were critically assessed for selection, and finally, 10 articles were included, comprising 5,116 patients (females = 60.2%; males = 39.8%) aged between 36-71 years. The included studies earned high quality ratings (6-9) based on the Newcastle-Ottawa-Scale criteria. Qualitative synthesis showed a significantly parallel relationship between increased CIMT and greater WMH burden in 50% of the studies. In addition, significant risk factors related to the CIMT-WMH association included older age, hypertension, depression, migraine, Hispanic ethnicity, and apolipoprotein E (ɛ4) in postmenopausal women.
CONCLUSION
Overall, the cumulative evidence showed a consistent CIMT-WMH association in asymptomatic middle-aged and older non-stroke adults, indicating that CAS may contribute to the progression of pathologically hyperintense white matter in the brain. However, further research is warranted to infer the plausible relationship between CIMT and WMH in the absence of stroke.
PubMed: 38903057
DOI: 10.3389/fnana.2024.1394766 -
Cortex; a Journal Devoted To the Study... May 2024The ε4 allele of the apolipoprotein E (APOE4) gene is an established risk factor for Alzheimer's disease but its impact on cognition in healthy adults across the... (Review)
Review
The ε4 allele of the apolipoprotein E (APOE4) gene is an established risk factor for Alzheimer's disease but its impact on cognition in healthy adults across the lifespan is unclear. One cognitive domain that is affected early in the course of Alzheimer's disease is spatial cognition, yet the evidence for APOE-related changes in spatial cognition is mixed. In this meta-analysis we assessed the impact of carrying the APOE4 allele on five subdomains of spatial cognition across the lifespan. We included studies of healthy human participants where an APOE4-carrier group (heterozygous or homozygous) could be compared to a homozygous group of APOE3-carriers. We identified 156 studies in total from three databases (Pubmed, Scopus and Web of Science) as well as through searching cited literature and contacting authors for unpublished data. 122 studies involving 32,547 participants were included in a meta-analysis, and the remaining studies are included in a descriptive review. APOE4 carriers scored significantly lower than APOE3 carriers (θˆ = -.08 [-.14, -.02]) on tests of spatial long-term memory; this effect was very small and was not modulated by age. On other subdomains of spatial cognition (spatial construction, spatial working memory, spatial reasoning, navigation) there were no effects of genotype. Overall, our results demonstrate that the APOE4 allele exerts little influence on spatial cognitive abilities in healthy adults.
PubMed: 38878339
DOI: 10.1016/j.cortex.2024.05.006 -
The Journal of Head Trauma... Jun 2024The purpose of this review is to systematically assess primary research publications on known genetic variants, which modify the risk for symptoms or dysfunction...
OBJECTIVE
The purpose of this review is to systematically assess primary research publications on known genetic variants, which modify the risk for symptoms or dysfunction persisting 30 days or more following mild traumatic brain injury (mTBI).
SUMMARY OF REVIEW
A search of PubMed and Embase from inception through June 2022 identified 42 studies that associated genetic variants with the presence of symptoms or cognitive dysfunction 30 days or more following mTBI. Risk of bias was assessed for each publication using the Newcastle Ottawa Scale (NOS). Fifteen of the 22 studies evaluating apolipoprotein E ( APOE ) ɛ4 concluded that it was associated with worse outcomes and 4 of the 8 studies investigating the brain-derived neurotrophic factor ( BDNF ) reported the Val66Met allele was associated with poorer outcomes. The review also identified 12 studies associating 28 additional variants with mTBI outcomes. Of these, 8 references associated specific variants with poorer outcomes. Aside from analyses comparing carriers and noncarriers of APOE ɛ4 and BDNF Val66Met, most of the reviewed studies were too dissimilar, particularly in terms of specific outcome measures but also in genes examined, to allow for direct comparisons of their findings. Moreover, these investigations were observational and subject to varying degrees of bias.
CONCLUSIONS
The most consistent finding across articles was that APOE ɛ4 is associated with persistent post-mTBI impairment (symptoms or cognitive dysfunction) more than 30 days after mTBI. The sparsity of other well-established and consistent findings in the mTBI literature should motivate larger, prospective studies, which characterize the risk for persistent impairment with standardized outcomes in mTBI posed by other genetic variants influencing mTBI recovery.
PubMed: 38668678
DOI: 10.1097/HTR.0000000000000907 -
Dementia and Geriatric Cognitive... Apr 2024Vascular dementia (VaD), a neurocognitive impairment directly related to vascular injury, is the second most common cause of age-related dementia. Although numerous...
INTRODUCTION
Vascular dementia (VaD), a neurocognitive impairment directly related to vascular injury, is the second most common cause of age-related dementia. Although numerous studies have investigated candidate genetic polymorphisms associated with VaD in Asia, the genetics of VaD remains unclear.
METHODS
This review provides an updated meta-analysis of genetic polymorphisms associated with VaD in Asians, using the PRISMA guidelines. Published literature up to May 2021 was extracted from the PubMed, Scopus, Ovid, and EBSCOhost databases. Meta-analysis was conducted using the Open Meta analyst, Review Manager, and MedCalc® Statistical Software. Trial sequential analysis (TSA) was performed using TSA viewer software.
RESULTS
A total of 46 eligible studies, comprising 23 genes and 35 single nucleotide polymorphisms, were retrieved. The meta-analysis was conducted on the following genetic polymorphisms, APOE ε2/3/4, MTHFR rs1801131, ACE rs4340 (I/D) gene polymorphism, and a PSEN1 intron 8 variant. The pooled odds ratio (ORs) revealed a significant increase in the risk of VaD in the apolipoprotein E (APOE) ε4 allelic model (OR, 1.79, p < 0.001), and the methylenetetrahydrofolate reductase (MTHFR) rs1801133 polymorphism T allele in the allelic model (OR, 1.23, p = 0.013).
CONCLUSION
Our findings provide evidence that genetic polymorphisms of the APOE ε4 allele and MTHFR rs1801133 T allele increase the risk of developing VaD in Asians. However, future large-scale investigations examining particularly on South-Eastern and West-Asian populations are highly recommended.
PubMed: 38636474
DOI: 10.1159/000538864 -
Preventive Nutrition and Food Science Dec 2023Plant sterols/stanols are effective cholesterol-lowering agents. However, it is unclear whether the apolipoprotein E () genetic variants influence it. We investigated... (Review)
Review
Plant sterols/stanols are effective cholesterol-lowering agents. However, it is unclear whether the apolipoprotein E () genetic variants influence it. We investigated whether genetic variants modulate the responses of blood lipids to dietary intervention plant sterols/stanols in adults and if the intervention dose and duration, as well as the age and status of participants, influence this effect. Randomized clinical trials were identified by searching databases in the Cochrane Library. Random-effect models were used to estimate the pooled effect size of each outcome of interest total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, and triglycerides. Meta-regression and subgroup analysis were used to investigate the effects of potential modifiers on the outcomes of interest. Eleven articles were selected from 3,248 retrieved abstracts. Plant sterol/stanol intervention was associated with a more significant reduction in LDL levels in the E3 group [-0.251 mmol/L; 95% confidence interval (95% CI), -0.488 to -0.015] compared with both the E4 and E2 groups. In E4 carriers, the plant sterol/stanol intervention dose and duration resulted in a larger decrease in LDL levels (-0.088027 mmol/L; 95% CI, -0.154690 to -0.021364). In conclusion, genetic variants affected the response of blood LDL levels to supplementation with plant sterols/stanols, as individuals with E3 variant showed significantly decreased LDL levels compared with the other genotypes. However, future studies recruiting participants according to their genetic variants are needed to confirm our conclusion.
PubMed: 38188084
DOI: 10.3746/pnf.2023.28.4.377 -
Journal of Alzheimer's Disease : JAD 2024Developing effective strategies for reducing dementia risk requires a detailed understanding of the risk and protective factors associated with the progression of mild...
BACKGROUND
Developing effective strategies for reducing dementia risk requires a detailed understanding of the risk and protective factors associated with the progression of mild cognitive impairment (MCI) to dementia.
OBJECTIVE
We aimed to systematically review the evidence for sex differences in these factors.
METHODS
Five online databases (PubMed/CINAHL/EMBASE/PsycINFO/Cochrane) were searched from inception until 17 October 2022 for cohort studies that focused on sex differences in risk and protective factors in the progression of MCI to dementia.
RESULTS
A total of 2,972 studies were identified, of which 12 studies from five countries were included in the systematic review. There was substantial variability in study designs, study populations and outcome measures. Sex differences were present in the associations of sociodemographic, health, psychological factors, genetic and other biomarkers with the progression of MCI to dementia. APOE ɛ4 status and depression appeared to increase the risk of progression for females, whereas history of stroke, MRI markers and cerebrospinal fluid biomarkers appeared to increase the risk of progression for males. APOE ɛ2 status and marital status (unmarried) were observed to reduce risk of progression in males and females, respectively.
CONCLUSIONS
The ability of studies to accurately detail risk factors for dementia are likely limited when solely controlling for the effects of sex. Although the heterogeneity and underpowered nature of the studies made it difficult to synthesize the findings for each risk factor, this study highlights the apparent need for further research examining risk factors for dementia in males and females with MCI separately.
Topics: Female; Humans; Male; Alzheimer Disease; Protective Factors; Sex Characteristics; Cognitive Dysfunction; Biomarkers; Apolipoproteins E; Disease Progression; Risk Factors
PubMed: 38143350
DOI: 10.3233/JAD-230700 -
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 -
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 -
Beneficial Effect of Societal Factors on APOE-ε2 and ε4 Carriers' Brain Health: A Systematic Review.The Journals of Gerontology. Series A,... Feb 2024Apolipoprotein-E (APOE) ε4 and ε2 are the most prevalent risk-increasing and risk-reducing genetic predictors of Alzheimer's disease, respectively. However, the extent...
BACKGROUND
Apolipoprotein-E (APOE) ε4 and ε2 are the most prevalent risk-increasing and risk-reducing genetic predictors of Alzheimer's disease, respectively. However, the extent to which societal factors can reduce the harmful impact of APOE-ε4 and enhance the beneficial impact of APOE-ε2 on brain health has not yet been examined systematically.
METHODS
To fill this gap, we conducted a systematic review searching for studies in MEDLINE, Embase, PsycINFO, and Scopus until June 2023, that included: (a) 1 of 5 social determinants of health (SDH) identified by Healthy People 2030, (b) APOE-ε2 or APOE-ε4 allele carriers, (c) cognitive or brain-biomarker outcomes, and (d) studies with an analysis of how APOE-ε2 and/ or APOE-ε4 carriers differ on outcomes when exposed to SDH.
RESULTS
From 14 076 articles retrieved, 124 met the inclusion criteria. In most of the studies, exposure to favorable SDH reduced APOE-ε4's detrimental effect and enhanced APOE-ε2's beneficial effect on cognitive and brain-biomarker outcomes (cognition: 70.5%, n: 74/105; brain-biomarkers: 71.4%, n: 20/28). A similar pattern of results emerged in each of the 5 Healthy People 2030 SDH categories, where finishing high school, having resources to satisfy basic needs, less air pollution, less negative external stimuli that can generate stress (eg, negative age stereotypes), and exposure to multiple favorable SDH were associated with better cognitive and brain health among APOE-ε4 and APOE-ε2 carriers.
CONCLUSIONS
Societal factors can reduce the harmful impact of APOE-ε4 and enhance the beneficial impact of APOE-ε2 on cognitive outcomes. This suggests that plans to reduce dementia should include community-level policies promoting favorable SDH.
Topics: Humans; Alleles; Alzheimer Disease; Apolipoprotein E2; Apolipoprotein E4; Apolipoproteins E; Biomarkers; Brain; Genotype
PubMed: 37792627
DOI: 10.1093/gerona/glad237 -
Journal of Alzheimer's Disease Reports 2023Alzheimer's disease (AD) has several risk factors. is the main one, and it has been suggested that there may be a synergy between it and as a risk factor.
Confirmed Synergy Between the ɛ4 Allele of Apolipoprotein E and the Variant K of Butyrylcholinesterase as a Risk Factor for Alzheimer's Disease: A Systematic Review and Meta-Analysis.
BACKGROUND
Alzheimer's disease (AD) has several risk factors. is the main one, and it has been suggested that there may be a synergy between it and as a risk factor.
OBJECTIVE
To investigate the association between and as a risk factor for AD.
METHODS
We searched PubMed, Web of Science, Embase, and Scopus on August 8, 2021 for studies that analyzed the association of and with AD. The random effect model was performed in meta-analysis according to age group. A chi-square was performed with the meta-analysis data to verify if the effect found is not associated only with the E4 allele.
RESULTS
Twenty-one studies with 6,853 subjects (3,528 AD and 3,325 Controls) were included in the meta-analysis. The quality of the evidence is moderate. There is a positive E4-K association for subjects with AD as shown by the odds ratio of 3.43. The chi-square meta test, which measures the probability that the E4-K association is due to chance, has an odds ratio of 6.155, indicating that the E4-K association is not a random event. The odds ratio of an E4-K association in subjects with AD increases to OR 4.46 for the 65- to 75-year-old group and OR 4.15 for subjects older than 75 years. The probability that the E4-K association is due to chance is ruled out by chi-square meta test values of OR 8.638 and OR 9.558.
CONCLUSION
The synergy between and is a risk factor for late-onset AD.
PubMed: 37483326
DOI: 10.3233/ADR-220084