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Alzheimer's Research & Therapy Nov 2020Possession of the ε4 allele of apolipoprotein E (APOE) is the primary genetic risk factor for the sporadic form of Alzheimer's disease (AD). While researchers have... (Review)
Review
Possession of the ε4 allele of apolipoprotein E (APOE) is the primary genetic risk factor for the sporadic form of Alzheimer's disease (AD). While researchers have extensively characterized the impact that APOE ε4 (APOE4) has on the susceptibility of AD, far fewer studies have investigated the phenotypic differences of patients with AD who are APOE4 carriers vs. those who are non-carriers. In order to understand these differences, we performed a qualitative systematic literature review of the reported cognitive and pathological differences between APOE4-positive (APOE4+) vs. APOE4-negative (APOE4-) AD patients. The studies performed on this topic to date suggest that APOE4 is not only an important mediator of AD susceptibility, but that it likely confers specific phenotypic heterogeneity in AD presentation, as well. Specifically, APOE4+ AD patients appear to possess more tau accumulation and brain atrophy in the medial temporal lobe, resulting in greater memory impairment, compared to APOE4- AD patients. On the other hand, APOE4- AD patients appear to possess more tau accumulation and brain atrophy in the frontal and parietal lobes, resulting in greater impairment in executive function, visuospatial abilities, and language, compared to APOE4+ AD patients. Although more work is necessary to validate and interrogate these findings, these initial observations of pathological and cognitive heterogeneity between APOE4+ vs. APOE4- AD patients suggest that there is a fundamental divergence in AD manifestation related to APOE genotype, which may have important implications in regard to the therapeutic treatment of these two patient populations.
Topics: Alzheimer Disease; Apolipoprotein E4; Apolipoproteins E; Atrophy; Cognition; Humans
PubMed: 33148345
DOI: 10.1186/s13195-020-00712-4 -
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 -
Ageing Research Reviews Dec 2020For decades, researchers have tried to understand the moderating effect of APOE ε4 carriage on the relationship between physical activity (PA), brain health and...
INTRODUCTION
For decades, researchers have tried to understand the moderating effect of APOE ε4 carriage on the relationship between physical activity (PA), brain health and dementia risk. However, this field has produced inconsistent findings.
METHOD
We conducted a systematic review of the literature, searching for observational and interventional studies examining the effect of APOE ε4 carriage on the relationships between PA, dementia risk and different markers of brain health.
RESULTS
Observational studies using dementia risk as a primary outcome measure generally found that in shorter follow-up periods (up to 10 years) both APOE ε4 carriers and non-carriers benefit from PA, although longer follow-ups showed mixed results. In neuroimaging studies, mainly carriers or both groups showed benefits. Additionally, the association between PA and amyloid burden was more evident among carriers. Overall, studies with greater samples of active APOE ε4 carriers are more likely to report benefits within this group in terms of lower dementia risk and reduced brain pathology.
DISCUSSION
Although we have identified some patterns for the modulating effect of APOE ε4 on PA and dementia or brain pathology, the available data is, overall, inconclusive. Heterogeneity in study design, methodology, and outcomes blur the ability to detect clear associations.
Topics: Alzheimer Disease; Apolipoprotein E4; Brain; Dementia; Exercise; Genotype; Humans
PubMed: 32961338
DOI: 10.1016/j.arr.2020.101173 -
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 -
Behavioural Brain Research Jan 2021This systematic review examined whether event-related potentials (ERPs) during higher cognitive processing can detect subtle, early signs of neurodegenerative disease....
This systematic review examined whether event-related potentials (ERPs) during higher cognitive processing can detect subtle, early signs of neurodegenerative disease. Original, empirical studies retrieved from PsycINFO and PubMed were reviewed if they analyzed patterns in cognitive ERPs (≥150 ms post-stimulus) differentiating mild cognitive impairment (MCI), Alzheimer's disease (AD), or cognitively intact elders who carry AD risk through the Apolipoprotein-E ε4 allele (ε4+) from healthy older adult controls (HC). The 100 studies meeting inclusion criteria (MCI = 47; AD = 47; ε4+ = 6) analyzed N200, P300, N400, and occasionally, later components. While there was variability across studies, patterns of reduced amplitude and delayed latency were apparent in pathological aging, consistent with AD-related brain atrophy and cognitive impairment. These effects were particularly evident in advanced disease progression (i.e., AD > MCI) and in later ERP components measured during complex tasks. Although ERP studies in intact ε4+ elders are thus far scarce, a similar pattern of delayed latency was notable, along with a contrasting pattern of increased amplitude, consistent with compensatory neural activation. This limited work suggests ERPs might be able to index early neural changes indicative of future cognitive decline in otherwise healthy elders. As ERPs are also accessible and affordable relative to other neuroimaging methods, their addition to cognitive assessment might substantively enhance early identification and characterization of neural dysfunction, allowing opportunity for earlier differential diagnosis and targeting of intervention. To evaluate this possibility there is urgent need for well-powered studies assessing late cognitive ERPs during complex tasks, particularly in healthy elders at risk for cognitive decline.
Topics: Alzheimer Disease; Cognitive Dysfunction; Evoked Potentials; Humans
PubMed: 32941881
DOI: 10.1016/j.bbr.2020.112904 -
Cognitive and Behavioral Neurology :... Sep 2020Air pollution has a negative impact on one's health and on the central nervous system. We decided to assess studies that evaluated the relationship between air pollution...
Air pollution has a negative impact on one's health and on the central nervous system. We decided to assess studies that evaluated the relationship between air pollution and cognitive functions in children and adolescents by reviewing studies that had been published between January 2009 and May 2019. We searched three major databases for original works (26 studies) and for studies using brain imaging methods based on MRI (six studies). Adverse effects of air pollutants on selected cognitive or psychomotor functions were found in all of the studies. Exposure to nitrogen dioxide, for example, was linked to impaired working memory, general cognitive functions, and psychomotor functions; particulate matter 2.5 was linked to difficulties in working memory, short-term memory, attention, processing speed, and fine motor function; black carbon was linked to poor verbal intelligence, nonverbal intelligence, and working memory; airborne copper was linked to impaired attentiveness and fine motor skills; isophorone was linked to lower mathematical skills; and polycyclic aromatic hydrocarbons in fetal life were linked to lower intelligence scores. The studies using MRI showed that high concentrations of air pollutants were linked to changes in the brain's white matter or lower functional integration and segregation in children's brain networks. In view of the global increase in air pollution, there is a need for further research to elucidate the relationship between air pollution and cognitive and motor development in children. According to some studies, neuroinflammation, the e4 allele of the apolipoprotein E gene, and gutathione-S-transferase gene polymorphism processes may play a role.
Topics: Air Pollution; Child; Cognitive Dysfunction; Environmental Exposure; Female; Humans; Male; Particulate Matter
PubMed: 32889949
DOI: 10.1097/WNN.0000000000000235 -
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 -
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 -
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 -
Neuroscience and Biobehavioral Reviews Jun 2020This systematic review examines the genetic and epigenetic factors associated with resting-state functional connectivity (RSFC) in healthy human adult brains across the... (Review)
Review
This systematic review examines the genetic and epigenetic factors associated with resting-state functional connectivity (RSFC) in healthy human adult brains across the lifespan, with a focus on genes associated with Alzheimer's disease (AD). There were 58 studies included. The key findings are: (i) genetic factors have a low to moderate contribution; (ii) the apolipoprotein E ε2/3/4 polymorphism was the most studied genetic variant, with the APOE-ε4 allele most consistently associated with deficits of the default mode network, but there were insufficient studies to determine the relationships with other AD candidate risk genes; (iii) a single genome-wide association study identified several variants related to RSFC; (iv) two epigenetic independent studies showed a positive relationship between blood DNA methylation of the SLC6A4 promoter and RSFC measures. Thus, there is emerging evidence that genetic and epigenetic variation influence the brain's functional organisation and connectivity over the adult lifespan. However, more studies are required to elucidate the roles genetic and epigenetic factors play in RSFC measures across the adult lifespan.
Topics: Adult; Aging; Brain; Brain Mapping; Genome-Wide Association Study; Humans; Magnetic Resonance Imaging; Neural Pathways; Rest; Serotonin Plasma Membrane Transport Proteins
PubMed: 32169413
DOI: 10.1016/j.neubiorev.2020.03.011