The Effect of the APOE-ε4 Allele and ACE-I/D Polymorphism on Cognition during a Two-Year Follow-Up in First-Ever Stroke Patients

2010 ◽  
Vol 29 (6) ◽  
pp. 534-542 ◽  
Author(s):  
A.M.J.J. Bour ◽  
S.M.C. Rasquin ◽  
L. Baars ◽  
M.P.J. van Boxtel ◽  
P.J. Visser ◽  
...  
Keyword(s):  
Stroke Patients ◽  
Apoe Ε4 ◽  
Ε4 Allele

scholarly journals SURVIVAL ADVANTAGE OF APOE2

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S621-S621
Author(s):  
Sudha Seshadri
Keyword(s):  
Lower Risk ◽  
Large Population ◽  
Population Based ◽  
European Ancestry ◽  
Aggregated Data ◽  
Risk Of Death ◽  
Apoe Ε4 ◽  
Increased Risk ◽  
Ε4 Allele

Abstract Apolipoprotein E is a glycoprotein mediator and regulator of lipid transport and uptake. The APOE-ε4 allele has been associated with higher risk of Alzheimer’s disease and of mortality, but the effect of the less prevalent APOE-ε2 on survival remains elusive. We aggregated data of 38,537 individuals of European ancestry (mean age 65.5 years; 55.6% women) from six large population-based cohorts to determine the association of APOE-ε2, with survival in the general population. During a mean follow-up of 11.7 years, 17,021 individuals died. Compared with homozygous APOE-ε3 carriers, APOE-ε2 carriers were at lower risk of death (hazard ratio,95% confidence interval: 0.94,0.90-0.99; P=1.1*10-2), whereas APOE-ε4 carriers were at increased risk (HR 1.17,1.12-1.21; P=2.8*10-16). Risk was lowest for homozygous APOE-ε2 (HR 0.89,0.74-1.08), and highest for homozygous APOE-ε4 (HR 1.52,1.37-1.70). Results did not differ by sex. The association was unaltered after adjustment for baseline LDL or cardiovascular disease. Larger, multiethnic collaborations are ongoing.

Cognitive impairment and the role of the ApoE ε4-allele after stroke-a 13 months follow-up study

2009 ◽  
Vol 25 (8) ◽  
pp. 833-842 ◽  
Author(s):  
Jørgen Wagle ◽  
Lasse Farner ◽  
Kjell Flekkøy ◽  
Torgeir B. Wyller ◽  
Leiv Sandvik ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Follow Up Study ◽  
Apoe Ε4 ◽  
Ε4 Allele

Hippocampal Volume Loss, Brain Amyloid Accumulation, and APOE Status in Cognitively Intact Elderly Subjects

2019 ◽  
Vol 19 (3-4) ◽  
pp. 139-147 ◽  
Author(s):  
Sven Haller ◽  
Marie-Louise Montandon ◽  
Cristelle Rodriguez ◽  
Valentina Garibotto ◽  
François R. Herrmann ◽  
...  
Keyword(s):  
Hippocampal Volume ◽  
Elderly Subjects ◽  
Neuropsychological Performance ◽  
Amyloid Pet ◽  
Volume Loss ◽  
Apoe Ε4 ◽  
Amyloid Accumulation ◽  
Ε4 Allele ◽  
The Impact

Background: Hippocampal volume loss (HVL), PET-documented brain amyloid accumulation, and APOE-ε4 status are predictive biomarkers of the transition from mild cognitive impairment to Alzheimer disease (AD). In asymptomatic cases, the role of these biomarkers remains ambiguous. In contrast to the idea that HVL occurs in late phases of neurodegeneration, recent contributions indicate that it might occur before abnormal amyloid PET occurrence in elderly subjects and that its severity could be only marginally related to APOE variants. Using a longitudinal design, we examined the determinants of HVL in our sample, i.e., brain amyloid burden and the presence of APOE-ε4, and made a longitudinal assessment of cognitive functions. Methods: We performed a 4.5-year longitudinal study on 81 elderly community dwellers (all right-handed;, 48 (59.3%) women; mean age 73.7 ± 3.7 years) including MRI at baseline and follow-up, PET amyloid during follow-up, neuropsychological assessment at 18 and 54 months, and APOE genotyping. All cases were assessed using a continuous cognitive score (CCS) that took into account the global evolution of neuropsychological performance. Linear regression models were used to identify predictors of HVL. Results: There was a negative association between the CCS and HVL bilaterally. In multivariate models adjusting for demographic variables, the presence of APOE-ε4 was related to increased HVL bilaterally. A trend of significance was observed with respect to the impact of amyloid positivity on HVL in the left hemisphere. No significant interaction was found between amyloid positivity and the APOE-ε4 allele. Conclusion: The progressive decrement of neuropsychological performance is associated with HVL long before the emergence of clinically overt symptoms. In this cohort of healthy individuals, the presence of the APOE-ε4 allele was shown to be an independent predictor of worst hippocampal integrity in asymptomatic cases independently of amyloid positivity.

scholarly journals APOE ε4 and the risk for Alzheimer disease and cognitive decline in African Americans and Yoruba

2014 ◽  
Vol 26 (6) ◽  
pp. 977-985 ◽  
Author(s):  
Hugh C. Hendrie ◽  
Jill Murrell ◽  
Olusegun Baiyewu ◽  
Kathleen A. Lane ◽  
Christianna Purnell ◽  
...  
Keyword(s):  
African Americans ◽  
Cognitive Decline ◽  
Proportional Hazards ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Community Dwelling ◽  
Apoe Ε4 ◽  
Ε4 Allele ◽  
E4 Allele

ABSTRACTBackground:There is little information on the association of the APOEe4 allele and AD risk in African populations. In previous analyses from the Indianapolis-Ibadan dementia project, we have reported that APOE ε4 increased the risk for Alzheimer's disease (AD) in African Americans but not in Yoruba. This study represents a replication of this earlier work using enriched cohorts and extending the analysis to include cognitive decline.Methods:In this longitudinal study of two community dwelling cohorts of elderly Yoruba and African Americans, APOE genotyping was conducted from blood samples taken on or before 2001 (1,871 African Americans & 2,200 Yoruba). Mean follow up time was 8.5 years for African Americans and 8.8 years for Yoruba. The effects of heterozygosity or homozygosity of ε4 and of the possession of e4 on time to incident AD and on cognitive decline were determined using Cox's proportional hazards regression and mixed effects models.Results:After adjusting for covariates, one or two copies of the APOE ε4 allele were significant risk factors for incident AD (p < 0.0001) and cognitive decline in the African-American population (p < 0001). In the Yoruba, only homozygosity for APOE ε4 was a significant risk factor for AD (p = 0.0002) but not for cognitive decline (p = 0.2346), however, possession of an e4 allele was significant for both incident AD (p = 0.0489) and cognitive decline (p = 0.0425).Conclusions:In this large longitudinal comparative study, APOE ε4 had a significant, but weaker, effect on incident AD and on cognitive decline in Yoruba than in African Americans. The reasons for these differences remain unclear.

Molecular Genetics of Early- and Late-Onset Alzheimer’s Disease

2020 ◽  
Vol 20 ◽  
Author(s):  
Md. Sahab Uddin ◽  
Sharifa Hasana ◽  
Md. Farhad Hossain ◽  
Md. Siddiqul Islam ◽  
Tapan Behl ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Massively Parallel Sequencing ◽  
Late Onset ◽  
Current Knowledge ◽  
The Elderly ◽  
Apoe Ε4 ◽  
Sequencing Technologies ◽  
Genetic Components ◽  
Ε4 Allele

: Alzheimer’s disease (AD) is the most common form of dementia in the elderly and this complex disorder is associated with environmental as well as genetic components. Early-onset AD (EOAD) and late-onset AD (LOAD, more common) are major identified types of AD. The genetics of EOAD is extensively understood with three genes variants such as APP, PSEN1, and PSEN2 leading to disease. On the other hand, some common alleles including APOE are effectively associated with LOAD identified but the genetics of LOAD is not clear to date. It has been accounted that about 5% to 10% of EOAD patients can be explained through mutations in the three familiar genes of EOAD. The APOE ε4 allele augmented the severity of EOAD risk in carriers, and APOE ε4 allele was considered as a hallmark of EOAD. A great number of EOAD patients, who are not genetically explained, indicate that it is not possible to identify disease- triggering genes yet. Although several genes have been identified through using the technology of next-generation sequencing in EOAD families including SORL1, TYROBP, and NOTCH3. A number of TYROBP variants were identified through exome sequencing in EOAD patients and these TYROBP variants may increase the pathogenesis of EOAD. The existence of ε4 allele is responsible for increasing the severity of EOAD. However, several ε4 allele carriers live into their 90s that propose the presence of other LOAD genetic as well as environmental risk factors that are not identified yet. It is urgent to find out missing genetics of EOAD and LOAD etiology to discover new potential genetics facets which will assist to understand the pathological mechanism of AD. These investigations should contribute to developing a new therapeutic candidate for alleviating, reversing and preventing AD. This article based on current knowledge represents the overview of the susceptible genes of EOAD, and LOAD. Next, we represent the probable molecular mechanism which might elucidate the genetic etiology of AD and highlight the role of massively parallel sequencing technologies for novel gene discoveries.

scholarly journals Disruption of Arterial Perivascular Drainage of Amyloid-β from the Brains of Mice Expressing the Human APOE ε4 Allele

PLoS ONE ◽  
2012 ◽  
Vol 7 (7) ◽  
pp. e41636 ◽  
Author(s):  
Cheryl A. Hawkes ◽  
Patrick M. Sullivan ◽  
Sarah Hands ◽  
Roy O. Weller ◽  
James A. R. Nicoll ◽  
...  
Keyword(s):  
Amyloid Β ◽  
Human Apoe ◽  
Apoe Ε4 ◽  
Ε4 Allele ◽  
Perivascular Drainage

scholarly journals Treatment with Diazepam in Acute Stroke Prevents Poststroke Seizures: A Substudy of the EGASIS Trial

2021 ◽  
pp. 1-6
Author(s):  
Julia H. van Tuijl ◽  
Elisabeth P.M. van Raak ◽  
Robert J. van Oostenbrugge ◽  
Albert P. Aldenkamp ◽  
Rob P.W. Rouhl
Keyword(s):  
Placebo Group ◽  
Acute Stroke ◽  
Incidence Rate Ratio ◽  
Day Treatment ◽  
Stroke Patients ◽  
Early Administration ◽  
Anterior Circulation ◽  
Double Blind

<b><i>Objective:</i></b> The frequency of seizures after stroke is high, with a severe impact on the quality of life. However, little is known about their prevention. Therefore, we investigated whether early administration of diazepam prevents the development of seizures in acute stroke patients. <b><i>Methods:</i></b> We performed a substudy of the EGASIS trial, a multicenter double-blind, randomized trial in which acute stroke patients were treated with diazepam or placebo for 3 days. Follow-up was after 2 weeks and 3 months. The occurrence of seizures was registered prospectively as one of the prespecified secondary outcomes. <b><i>Results:</i></b> 784 EGASIS patients were eligible for this substudy (389 treated with diazepam [49.6%] and 395 treated with placebo [50.4%]). Seizures were reported in 19 patients (2.4% of the total patient group). Seizures occurred less frequently in patients treated with diazepam (1.5 vs. 3.3% in the placebo group); however, this difference was only statistically significant in patients with a cortical anterior circulation infarction (0.9% in the diazepam group vs. 4.6% in the placebo group, incidence rate ratio 0.20, 95% CI: 0.05–0.78, <i>p</i> = 0.02, NNT = 27). <b><i>Conclusion:</i></b> We found that a 3-day treatment with diazepam after acute cortical anterior circulation stroke prevents the occurrence of seizures in the first 3 months following stroke.

scholarly journals Decline in verbal memory during preclinical Alzheimer's disease: Examination of the effect of APOE genotype

2002 ◽  
Vol 8 (7) ◽  
pp. 943-955 ◽  
Author(s):  
KELLY L. LANGE ◽  
MARK W. BONDI ◽  
DAVID P. SALMON ◽  
DOUGLAS GALASKO ◽  
DEAN C. DELIS ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Episodic Memory ◽  
Verbal Memory ◽  
Verbal Learning ◽  
Apoe Genotype ◽  
Apoe Ε4 ◽  
Dementia Syndrome ◽  
Ε4 Allele

A subtle decline in episodic memory often occurs prior to the emergence of the full dementia syndrome in nondemented older adults who develop Alzheimer's disease (AD). The APOE-ε4 genotype may engender a more virulent form of AD that hastens this decline. To examine this possibility, we compared the rate of decline in episodic memory during the preclinical phase of AD in individuals with or without at least one APOE ε4 allele. Nondemented normal control (NC; n = 84) participants, nondemented older adults who subsequently developed dementia within 1 or 2 years (i.e., preclinical AD; n = 20), and patients with mild AD (n = 53) were examined with 2 commonly employed tests of episodic memory, the Logical Memory subtest of the Wechsler Memory Scale–Revised and the California Verbal Learning Test. Results revealed a precipitous decline in verbal memory abilities 1 to 2 years prior to the onset of the dementia syndrome, but there was little effect of APOE genotype on the rate of this memory decline. The presence of an APOE-ε4 allele, however, did have a differential effect on the sensitivity of the 2 types of memory tests for tracking progression and made an independent contribution to the prediction of conversion to AD. (JINS, 2002, 8, 943–955.)

P4-189: Effect of the APOE-ε4 allele on longitudinal changes in cortical thickness in normal aging

2012 ◽  
Vol 8 (4S_Part_19) ◽  
pp. P702-P703
Author(s):  
Tara Madhyastha ◽  
Paul Borghesani ◽  
Elizabeth Aylward ◽  
Monique Cherrier ◽  
Katie Askren ◽  
...  
Keyword(s):  
Cortical Thickness ◽  
Normal Aging ◽  
Longitudinal Changes ◽  
Apoe Ε4 ◽  
Ε4 Allele

Abstract WP47: Reperfusion Following Ischemic Stroke is Associated with Reduced Brain Edema

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Hannah J Irvine ◽  
Thomas W Battey ◽  
Ann-Christin Ostwaldt ◽  
Bruce C Campbell ◽  
Stephen M Davis ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Brain Edema ◽  
Infarct Volume ◽  
Brain Magnetic Resonance Imaging ◽  
Lesion Volume ◽  
Stroke Patients ◽  
Early Reperfusion ◽  
Echoplanar Imaging ◽  
Swelling Volume

Introduction: Revascularization is a robust therapy for acute ischemic stroke, but animal studies suggest that reperfusion edema may attenuate its beneficial effects. In stroke patients, early reperfusion consistently reduces infarct volume and improves long-term functional outcome, but there is little clinical data available regarding reperfusion edema. We sought to elucidate the relationship between reperfusion and brain edema in a patient cohort of moderate to severe stroke. Methods: Seventy-one patients enrolled in the Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET) with serial brain magnetic resonance imaging and perfusion-weighted imaging (PWI) were analyzed. Reperfusion percentage was calculated based on the difference in PWI lesion volume at baseline and follow-up (day 3-5). Midline shift (MLS) was measured on the day 3-5 fluid attenuated inversion recovery (FLAIR) sequence. Swelling volume and infarct growth volume were assessed using region-of-interest analysis on the baseline and follow-up DWI scans based on our prior methods. Results: Greater percentage of reperfusion was associated with less MLS (Spearman ρ = -0.46; P <0.0001) and reduced swelling volume (Spearman ρ = -0.56; P <0.0001). In multivariate analysis, reperfusion was an independent predictor of less MLS ( P <0.006) and decreased swelling volume ( P <0.0054), after adjusting for age, baseline NIHSS, admission blood glucose, baseline DWI volume, and IV tPA treatment. Conclusions: Reperfusion is associated with reduced brain edema as measured by MLS and swelling volume. While our data do not exclude the possibility of reperfusion edema in certain circumstances, in stroke patients, reperfusion following acute stroke is predominantly linked to less brain swelling.

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