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Journal of Alzheimer's Disease : JAD 2020Dementia is a devastating condition for older adults, with both modifiable (e.g., diabetes mellitus) and unmodifiable risk factors (e.g., APOEɛ4 allele). It remains... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dementia is a devastating condition for older adults, with both modifiable (e.g., diabetes mellitus) and unmodifiable risk factors (e.g., APOEɛ4 allele). It remains unclear how, and to what extent, diabetes impacts dementia risk via both cerebrovascular and amyloid-β pathways.
OBJECTIVE
We conducted a quantitative meta-analysis to investigate the contribution of diabetes to incident dementia risk in people with ɛ4 and, based on the vascular-related neuropathology of diabetes, whether the combination of these factors increases risk for vascular dementia versus Alzheimer's disease (AD).
METHODS
Systematic literature searches were conducted using EMBASE, MEDLINE, PsycINFO, and CINAHL databases. Pooled relative risk (RR) estimates were calculated using a random effects model, and subgroup analyses conducted across dementia subtypes.
RESULTS
Twelve studies were included, with a total of 16,200 participants. Considered concurrently, diabetes increased incident dementia risk an additional 35% for those with ɛ4 (RR = 1.35, 95% CI = 1.13-1.63). Similar patterns were observed for AD and vascular dementia.
CONCLUSION
Interventions to prevent co-morbid diabetes, and diabetes-related complications and neuropathological changes, may be one way of modifying dementia risk in the vulnerable ɛ4 population.
Topics: Aged; Alzheimer Disease; Apolipoprotein E4; Dementia; Dementia, Vascular; Diabetes Complications; Heterozygote; Humans; Risk Factors
PubMed: 32250298
DOI: 10.3233/JAD-191068 -
Frontiers in Aging Neuroscience 2021Consensus is lacking with regard to whether hearing loss is an independent risk factor for dementia. We therefore conducted a meta-analysis to clarify the relationship...
Consensus is lacking with regard to whether hearing loss is an independent risk factor for dementia. We therefore conducted a meta-analysis to clarify the relationship of hearing loss and dementia. Prospective cohort studies investigating the association between hearing loss and the incidence of dementia in a community-derived population were included by searching electronic databases that included PubMed, Embase, and Cochrane's Library. A random-effects model was adopted to combine the results. Fourteen cohorts including 726,900 participants were analyzed. It was shown that hearing loss was independently associated with dementia [adjusted hazard ratio (HR): 1.59, 95% confidence interval (CI): 1.37 to 1.86, < 0.001; = 86%]. Sensitivity analysis sequentially excluding any of the individual studies included showed similar results. Subgroup analysis according to the diagnostic methods for hearing loss, validation strategy for dementia, follow-up duration, and adjustment of apolipoprotein E genotype also showed consistent results (-values for subgroup differences all > 0.05). Meta-analysis with five studies showed that hearing loss was also connected to higher risk of Alzheimer's disease (adjusted HR: 2.24, 95% CI: 1.32 to 3.79, = 0.003; = 2%). Hearing loss may increase the risk of dementia in the adult population. Whether effective treatment for hearing loss could reduce the incidence of dementia should be explored in the future.
PubMed: 34305572
DOI: 10.3389/fnagi.2021.695117 -
Mymensingh Medical Journal : MMJ Oct 2020Stroke is one of the commonest causes of mortality among the world. Hemorrhagic stroke accounts nearly 15% of all the strokes. Different risk factors have been... (Meta-Analysis)
Meta-Analysis
Stroke is one of the commonest causes of mortality among the world. Hemorrhagic stroke accounts nearly 15% of all the strokes. Different risk factors have been identified, of them hypertension, anti-coagulation therapy and previous history of ischemic strokes are significant. Regarding the genetic causes of intracerebral hemorrhage (ICH) monogenic causes play a small role. It was found that Apolipoprotein E (APOE) gene has a strong association with ICH. This is a 299 amino acids long protein located in chromosome 19. APOE has three alleles, they are epsilon 2, 3 and 4. Total 10 meta-analysis were reviewed in this article which involved 52,705 participants. When looking for the association, ∈2 and ∈4 showed positive and ∈3 showed negative association with ICH. Association of ∈4 (OR mean 1.77) was stronger than that of ∈2 (OR mean 1.71).
Topics: Apolipoproteins E; Cerebral Hemorrhage; Genetic Predisposition to Disease; Genotype; Humans; Risk Factors; Stroke
PubMed: 33116113
DOI: No ID Found -
International Urogynecology Journal Jan 2020A contribution of genetic factors to the development of stress urinary incontinence (SUI) is broadly acknowledged. This study aimed to: (1) provide insight into the...
INTRODUCTION
A contribution of genetic factors to the development of stress urinary incontinence (SUI) is broadly acknowledged. This study aimed to: (1) provide insight into the genetic pathogenesis of SUI by gathering and synthesizing the available data from studies evaluating differential gene expression in SUI patients and (2) identify possible novel therapeutic targets and leads.
METHODS
A systematic literature search was conducted through September 2017 for the concepts of genetics and SUI. Gene networking connections and gene-set functional analyses of the identified genes as differentially expressed in SUI were performed using GeneMANIA software.
RESULTS
Of 3019 studies, 4 were included in the final analysis. A total of 13 genes were identified as being differentially expressed in SUI patients. Eleven genes were overexpressed: skin-derived antileukoproteinase (SKALP/elafin), collagen type XVII alpha 1 chain (COL17A1), plakophilin 1 (PKP1), keratin 16 (KRT16), decorin (DCN), biglycan (BGN), protein bicaudal D homolog 2 (BICD2), growth factor receptor-bound protein 2 (GRB2), signal transducer and activator of transcription 3 (STAT3), apolipoprotein E (APOE), and Golgi SNAP receptor complex member 1 (GOSR1), while two genes were underexpressed: fibromodulin (FMOD) and glucocerebrosidase (GBA). GeneMANIA revealed that these genes are involved in intermediate filament cytoskeleton and extracellular matrix organization.
CONCLUSION
Many genes are involved in the pathogenesis of SUI. Furthermore, whole-genome studies are warranted to identify these genetic connections. This study lays the groundwork for future research and the development of novel therapies and SUI biomarkers in clinical practice.
Topics: Gene Expression; Humans; Urinary Incontinence, Stress
PubMed: 31312847
DOI: 10.1007/s00192-019-04025-5 -
Journal of Alzheimer's Disease : JAD 2020Numerous studies have reported on cerebrospinal fluid (CSF) and blood biomarkers of Alzheimer's disease (AD); however, to date, none has compared biomarker patterns... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Numerous studies have reported on cerebrospinal fluid (CSF) and blood biomarkers of Alzheimer's disease (AD); however, to date, none has compared biomarker patterns across the early-onset subtypes, i.e., early onset sporadic AD (EOsAD) and autosomal dominant AD (ADAD), qualitatively and quantitatively.
OBJECTIVE
To compare the fluid biomarker patterns in early-onset subtypes of AD; EOsAD and ADAD.
METHODS
Six scientific databases were searched for peer-reviewed research publications. The total number of individuals used in all the meta-analysis were 2,427, comprised of 1,337 patients and 1,090 controls.
RESULTS
In the subset of EOsAD cases without APP, PSEN1/PSEN2 mutations, CSF Aβ42 and tau levels were higher when compared to the EOsAD group as a whole. Prevalence of the APOEɛ4 allele was more elevated in EOsAD relative to controls, and not significantly elevated in ADAD cases.
CONCLUSION
Established CSF biomarkers confirmed quantitative differences between variants of EOAD. EOsAD is enriched with APOEɛ4, but the level is not higher than generally reported in late-onset AD. The results prompt further exploration of the etiopathogenesis of EOsAD, which accounts for ∼4-10% of all AD cases, but the reasons for the early onset remain poorly understood.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Apolipoproteins E; Biomarkers; Humans; tau Proteins
PubMed: 32333592
DOI: 10.3233/JAD-200052 -
Clinical EEG and Neuroscience May 2021Apolipoprotein ε4 allele () is the strongest genetic risk factor for Alzheimer's disease and seems to be related to cognitive decline and damaged event-related...
BACKGROUND
Apolipoprotein ε4 allele () is the strongest genetic risk factor for Alzheimer's disease and seems to be related to cognitive decline and damaged event-related potential P300, which is a sensitive measure to assess cognitive processing.
OBJECTIVE
This research aims to critically review the existing scientific evidence regarding the association between and P300.
METHODS
A systematic review was carried out up to January 2020 on the following databases: Web of Science, Scopus and Medline/PubMed. Articles were considered for inclusion if they are original research that provided information regarding the association between and P300, available in English, Spanish, or Portuguese, and available in full text. The methodological quality of the studies selected was evaluated using the quality assessment tool for observational cohort and cross-sectional studies recommended by Cochrane.
RESULTS
Out of 993 studies, 14 met the inclusion criteria. The results obtained showed that is related to a longer P300 latency. However, the data supplied do not allow us to confirm if this relationship also occurs in amplitude measures. Moreover, it was observed that genotype may influence P300 in different ages, from younger individuals to demented older people.
CONCLUSION
Evidence shows that negatively influences cortical activities related to cognitive functions, as indicated by P300.
Topics: Aged; Aged, 80 and over; Alzheimer Disease; Apolipoprotein E4; Cross-Sectional Studies; Electroencephalography; Event-Related Potentials, P300; Humans
PubMed: 32945192
DOI: 10.1177/1550059420959966 -
Neuropsychology Review Dec 2023First-degree relatives of individuals with late-onset Alzheimer's disease (LOAD) are at increased risk for developing dementia, yet the associations between family... (Meta-Analysis)
Meta-Analysis Review
First-degree relatives of individuals with late-onset Alzheimer's disease (LOAD) are at increased risk for developing dementia, yet the associations between family history of LOAD and cognitive dysfunction remain unclear. In this quantitative review, we provide the first meta-analysis on the cognitive profile of unaffected first-degree blood relatives of LOAD-affected individuals compared to controls without a family history of LOAD. A systematic literature search was conducted in PsycINFO, PubMed /MEDLINE, and Scopus. We fitted a three-level structural equation modeling meta-analysis to control for non-independent effect sizes. Heterogeneity and risk of publication bias were also investigated. Thirty-four studies enabled us to estimate 218 effect sizes across several cognitive domains. Overall, first-degree relatives (n = 4,086, mean age = 57.40, SD = 4.71) showed significantly inferior cognitive performance (Hedges' g = -0.16; 95% CI, -0.25 to -0.08; p < .001) compared to controls (n = 2,388, mean age = 58.43, SD = 5.69). Specifically, controls outperformed first-degree relatives in language, visuospatial and verbal long-term memory, executive functions, verbal short-term memory, and verbal IQ. Among the first-degree relatives, APOE ɛ4 carriership was associated with more significant dysfunction in cognition (g = -0.24; 95% CI, -0.38 to -0.11; p < .001) compared to non-carriers (g = -0.14; 95% CI, -0.28 to -0.01; p = .04). Cognitive test type was significantly associated with between-group differences, accounting for 65% (R = .6499) of the effect size heterogeneity in the fitted regression model. No evidence of publication bias was found. The current findings provide support for mild but robust cognitive dysfunction in first-degree relatives of LOAD-affected individuals that appears to be moderated by cognitive domain, cognitive test type, and APOE ɛ4.
Topics: Humans; Middle Aged; Alzheimer Disease; Cognition; Cognitive Dysfunction; Cognition Disorders; Neuropsychological Tests; Apolipoproteins E
PubMed: 36057684
DOI: 10.1007/s11065-022-09555-2 -
Cardiology and Therapy Jun 2021Alzheimer's disease (AD) is a progressive neurodegenerative disease for which no effective treatment exists at present. Previous research has found that exercise reduces... (Review)
Review
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.
PubMed: 33403644
DOI: 10.1007/s40119-020-00209-z -
The Journal of Nutrition, Health & Aging 2021Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disease. The strongest genetic risk factor for sporadic AD is carriage of the ε4 allele of the...
Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disease. The strongest genetic risk factor for sporadic AD is carriage of the ε4 allele of the Apolipoprotein E (APOE) gene. Strategies to slow the progression of AD, including dietary interventions, may be modified by the pathogenic effect of this polymorphism. Our objective in this review was to determine the extent and quality of the literature investigating how dietary factors and interventions interact with the APOE ε4 genotype to impact cognitive decline in AD. To that end, we performed a systematic scoping review of published English-language articles involving human subjects. We found evidence suggesting that adherence to a Mediterranean diet may reduce cognitive decline among APOE ε4 carriers, whereas ketogenic agents appear to be ineffective. Diets high in saturated fats may be particularly harmful for APOE ε4 carriers. We identified several topics, including the use of ω-3 fatty acid and antioxidant supplements, for which additional high level evidence is needed.
Topics: Alleles; Alzheimer Disease; Apolipoprotein E4; Cognitive Dysfunction; Diet; Genotype; Humans; Neurodegenerative Diseases
PubMed: 34866144
DOI: 10.1007/s12603-021-1705-4 -
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