Prospective memory performance in veterans with and without histories of mild traumatic brain injury: effect of the apolipoprotein E (APOE) ε4 genotype.

OBJECTIVE: Identifying factors that moderate cognitive outcomes following mild traumatic brain injury (mTBI) is crucial. Prospective memory (PM) is a cognitive domain of interest in mTBI recovery as it may be especially sensitive to TBI-related changes. Since studies show that genetic status - particularly possession of the apolipoprotein E (APOE) ε4 allele - can modify PM performance, we investigated associations between mTBI status and APOE-ε4 genotype on PM performance in a well-characterized sample of Veterans with neurotrauma histories. METHODS: 59 Veterans (mTBI = 33, Military Controls [MCs] = 26; age range: 24-50; average years post-injury = 10.41) underwent a structured clinical interview, neuropsychological assessment, and genotyping. The Memory for Intentions Test (MIST) measured PM across multiple subscales. ANCOVAs, adjusting for age and posttraumatic stress symptoms, tested the effects of mTBI status (mTBI vs. MC) and ε4 status (ε4+ vs. ε4-) on MIST scores. RESULTS: Veterans with mTBI history performed more poorly compared to MCs on the MIST 15-min delay (p=.002, ηp2 =.160), Time Cue (p = .003, ηp2 =.157), and PM Total (p = .016, ηp2 =.102). Those with at least one copy of the ε4 allele performed more poorly compared to ε4- Veterans on the MIST 15-min delay (p = .011, ηp2 =.113) and PM Total (p = .048, ηp2 = .071). No significant interactions were observed between mTBI and APOE-ε4 status on MIST outcomes (ps>.25). Within the mTBI group, APOE-ε4+ Veterans performed worse than APOE-ε4- Veterans on the MIST 15-min delay subscale (p = .031, ηp2 = .150). CONCLUSIONS: mTBI history and APOE-ε4 genotype status were independently associated with worse PM performance compared to those without head injury histories or possession of the APOE-e4 genotype. Performance on the MIST 15-min delay was worse in Veterans with both risk factors (mTBI history and APOE-ε4 positivity). Findings suggest that genetic status may modify outcomes even in relatively young Veterans with mTBI histories. Future research examining longitudinal associations and links to neuroimaging and biomarker data are needed.

Association of Cognitive Impairment With Chronic Viral Hepatitis Among Older Adults in Taiwan.

OBJECTIVE: To evaluate the risk of cognitive impairment among patients with chronic viral hepatitis. DESIGN: A cross-sectional study. SETTING: Population-based. PARTICIPANTS: Individuals 60 years or older were enrolled from the Taiwan Biobank database from 2012. EXPOSURE: Hepatitis B virus and hepatitis C virus infections. MEASUREMENT: Cognitive impairment was evaluated using the mini-mental state examination (MMSE). Logistic regression models were used to calculate odds ratios and 95% confidence intervals (CIs). The effects of APOE ε4 polymorphisms on the association between viral hepatitis and the risk of cognitive impairment were also investigated. RESULTS: We recruited 912 participants with cognitive impairment and 22 869 participants without cognitive impairment. The adjusted odds ratio (aOR) for cognitive impairment was 1.38 (95% CI: 1.03-1.85, p = 0.033) among participants with hepatitis C virus infection and 1.14 (95% CI: 0.91-1.43, p = 0.257) among participants with hepatitis B virus infection. Participants with hepatitis C virus infection and without hepatitis B virus infection had a higher risk of cognitive impairment (aOR: 1.52, 95% CI: 1.13-2.04, p = 0.006). The MMSE subcategories most associated with hepatitis C virus infection were orientation and design copying. The association between hepatitis C virus infection and cognitive impairment was higher among participants with ε4 alleles of the APOE gene than among those without alleles (aOR: 2.18, 95% CI: 1.21-3.91, p = 0.009). CONCLUSIONS: Our findings suggest that individuals 60 years or older with chronic hepatitis C virus infection are at increased risk of cognitive impairment.

Neurobiological correlation between phosphorylated tau and mood symptoms in memory clinic patients.

BACKGROUND: Alzheimer's disease (AD) dementia and mild cognitive impairment are characterised by impaired cognition accompanied by neuropsychiatric symptoms (NPS) relating to mood, including depression, anxiety, and apathy. However, the utility of AD biomarkers for predicting mood symptoms of NPS remains controversial. Herein, we analyzed the relationship between phosphorylated tau (p-tau) and depression, anxiety, and apathy of NPS. We also examined the influence of genetic factors such as apolipoprotein E (APOE) ε4 on these relationships. METHODS: We conducted a cross-sectional survey in older patients (n = 122) with normal cognition (n = 12), mild cognitive impairment (n = 46), and AD (n = 64) strictly diagnosed by the board of psychiatrists and neurologists of Hokkaido University. NPS of the patients were assessed using the Neuropsychiatric Inventory Questionnaire (NPI). All patients also received a lumbar puncture to obtain cerebral spinal fluid for assessment of p-tau. The inverse probability weighting method was used to adjust for demographic differences between the p-tau present group and the p-tau absent group. RESULTS: There was an association between p-tau accumulation and decreased incidence of depression and apathy. APOE ε4 non-carriers also showed a trend toward a negative association between p-tau and depression, which was not evident in APOE ε4 carriers. CONCLUSIONS: We provide new evidence for a negative correlation between p-tau and depression and apathy of NPS, which may be influenced by APOE ε4. Future longitudinal studies are required to confirm the utility of p-tau for predicting the course of mood symptoms in patients with cognitive decline.

Associations Between Amyloid Burden, Hypoxemia, Sleep Architecture, and Cognition in Obstructive Sleep Apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with an increased risk of amyloid-ß (Aß) burden, the hallmark of Alzheimer's disease, and cognitive decline. OBJECTIVE: To determine the differential impacts of hypoxemia and slow-wave sleep disruption on brain amyloid burden, and to explore the effects of hypoxemia, slow-wave sleep disruption, and amyloid burden on cognition in individuals with and without OSA. METHODS: Thirty-four individuals with confirmed OSA (mean±SD age 57.5±4.1 years; 19 males) and 12 healthy controls (58.5±4.2 years; 6 males) underwent a clinical polysomnogram, a NAV4694 positron emission tomography (PET) scan for Aß burden, assessment of APOEɛ status and cognitive assessments. Linear hierarchical regressions were conducted to determine the contributions of demographic and sleep variables on amyloid burden and cognition. RESULTS: Aß burden was associated with nocturnal hypoxemia, and impaired verbal episodic memory, autobiographical memory and set shifting. Hypoxemia was correlated with impaired autobiographical memory, and only set shifting performance remained significantly associated with Aß burden when controlling for sleep variables. CONCLUSIONS: Nocturnal hypoxemia was related to brain Aß burden in this sample of OSA participants. Aß burden and hypoxemia had differential impacts on cognition. This study reveals aspects of sleep disturbance in OSA that are most strongly associated with brain Aß burden and poor cognition, which are markers of early Alzheimer's disease. These findings add weight to the possibility that hypoxemia may be causally related to the development of dementia; however, whether it may be a therapeutic target for dementia prevention in OSA is yet to be determined.

Age and sex differences in the association between APOE genotype and Alzheimer's disease in a Taiwan Chinese population.

Introduction: The Apolipoprotein E (APOE) epsilon (ε) 4 allele is a well-established risk factor for late-onset Alzheimer's disease (AD). Reports on white ancestry populations have showed that age, sex, and ethnicity have different effects on the association between APOE genotype and AD. However, studies on Asian populations such as Taiwan Chinese populations are limited. This study aimed to evaluate the association between APOE genotype and AD in a Taiwan Chinese population, and to explore if the association varies by age and sex. Methods: We conducted a case-control study in 725 patients with AD and 1,067 age- and sex- matched controls without dementia from a Taiwan Chinese population. Logistic regression models were used to test the association between AD and APOE genotypes. Secondary analyses considered age (<75 or ≥75 years old), and sex stratified models. Results: The risk of AD was significantly increased for people with at least one copy of APOE ε4 (OR = 2.52, 95% CI = 2.01-3.17, p < 0.001) and in a dose-dependent manner. Our results did not show an statistically significance different in AD risk when women and men carrying APOEε4 were compared. Despite not reaching statistical significance, the risk of APOE ε4 for AD was higher among younger participants (OR = 3.21, 95% CI = 2.26-4.56, p < 0.001) compared to older ones (OR = 2.13, 95% CI = 1.53-2.97, p < 0.001). When considering both sex and age, the risk of AD was higher among older men carrying APOE ε4 (OR = 2.64, 95% CI = 1.51-4.60 in men; OR = 1.90, 95% CI = 1.26-2.86 in women), while women carrying APOE ε4 appeared to have an increased risk at a younger age (OR = 3.29, 95% CI = 2.20-4.93 in women; OR = 2.91, 95% CI = 1.40-6.05 in men). Discussion: The APOE ε4 allele represents a major risk factor for AD in the Taiwanese population. The effect of APOE ε4 allele on AD risk appeared to be stronger among men aged 75 years or more and among younger women.

Exploration of acupuncture therapy in the treatment of MCI patients with the ApoE ε4 gene based on the brain-gut axis theory.

BACKGROUND: Mild cognitive impairment (MCI) is the predementia phase of Alzheimer's disease (AD). The intestinal microbiome is altered in MCI and AD, and apolipoprotein E (ApoE) ε4 gene polymorphism is a risk factor for the progression of MCI to AD. This study aims to investigate the improvement in cognitive function of MCI patients with and without ApoE ε4 due to acupuncture and the changes in gut microbiota community composition and abundance in MCI. METHODS: This randomized assessor-blind controlled study will enrol MCI patients with and without the ApoE ε4 gene (n = 60/60). Sixty subjects with the ApoE ε4 gene and 60 subjects without the ApoE ε4 gene will be randomly allocated into treatment and control groups in a 1:1 ratio. Intestinal microbiome profiles will be evaluated by 16 S rRNA sequencing of faecal samples and compared between the groups. RESULTS/CONCLUSIONS: Acupuncture is an effective method to improve cognitive function in MCI. This study will provide data on the relationship between the gut microbiota and the effectiveness of acupuncture in patients with MCI from a new angle. This study will also provide data on the relationship between the gut microbiota and an AD susceptibility gene by integrating microbiologic and molecular approaches. TRIAL REGISTRATION: www.chictr.org.cn , ID: ChiCTR2100043017, recorded on 4 February 2021.

Prevailing Antagonistic Risks in Pleiotropic Associations with Alzheimer's Disease and Diabetes.

BACKGROUND: The lack of efficient preventive interventions against Alzheimer's disease (AD) calls for identifying efficient modifiable risk factors for AD. As diabetes shares many pathological processes with AD, including accumulation of amyloid plaques and neurofibrillary tangles, insulin resistance, and impaired glucose metabolism, diabetes is thought to be a potentially modifiable risk factor for AD. Mounting evidence suggests that links between AD and diabetes may be more complex than previously believed. OBJECTIVE: To examine the pleiotropic architecture of AD and diabetes mellitus (DM). METHODS: Univariate and pleiotropic analyses were performed following the discovery-replication strategy using individual-level data from 10 large-scale studies. RESULTS: We report a potentially novel pleiotropic NOTCH2 gene, with a minor allele of rs5025718 associated with increased risks of both AD and DM. We confirm previously identified antagonistic associations of the same variants with the risks of AD and DM in the HLA and APOE gene clusters. We show multiple antagonistic associations of the same variants with AD and DM in the HLA cluster, which were not explained by the lead SNP in this cluster. Although the ɛ2 and ɛ4 alleles played a major role in the antagonistic associations with AD and DM in the APOE cluster, we identified non-overlapping SNPs in this cluster, which were adversely and beneficially associated with AD and DM independently of the ɛ2 and ɛ4 alleles. CONCLUSION: This study emphasizes differences and similarities in the heterogeneous genetic architectures of AD and DM, which may differentiate the pathogenic mechanisms of these diseases.

Apolipoprotein-E Gene Polymorphism and Lipid Composition among IUGR and AGA Neonates.

Objective The objective of this study is to study the profile of apolipoprotein E ( APOE ) gene polymorphism and lipid profile among intrauterine growth restriction (IUGR) and appropriate for gestational age (AGA) neonates. This is an observational study. This study was done at the neonatal unit of a teaching hospital in South India. All consecutively born IUGR neonates (cases) of more than 32 weeks' gestational age and AGA neonates (controls) were enrolled for the study. Genomic DNA extraction was done from a total of 102 peripheral venous blood samples. Genotyping of the APOE rs429358 and rs7412 defining the ε2, ε3, and ε4 alleles was done by polymerase chain reaction-restriction fragment length polymorphism method. Prefeed venous blood was collected and analyzed for lipid profile estimation. The allelic frequencies of cases versus control were ε2-9 (8.7%) versus 3 (2.9%); ε3-88 (84.6%) versus 81 (79.4%); and ε4-7 (6.7%) versus 18 (17.6%). The frequency of ε4 isoform allele, associated with adult onset of metabolic diseases was less among the IUGR group. The mean total cholesterol (TC), Low-Density Lipoprotein (LDL), High-Density Lipoprotein, and triglyceride (TG) were 107.59 ± 35.99, 51.69 ± 24.68, 21.75 ± 9.58, and 151.22 ± 61.84 mg/dL, respectively, in the IUGR group. The mean TC and LDL levels in IUGR group were marginally higher than AGA neonates (107 ± 35.99 vs. 100.37 ± 22.69 mg/dL and 51.69 ± 24.68 versus 46.9 ± 19.51 mg/dL, p > 0.05). In both groups, the mean TC and TGL levels were elevated in the ε4 isoform subgroup ( p > 0.05). In our study, the ε2 allele was the second most predominant APOE isoform and the ε4 allele of the APOE gene associated with adult-onset diseases was not increased among IUGR neonates. Neonates with ε4 allele showed an abnormal lipid profile in both study groups suggesting a possible association.

Effect of Ethyl Acetate Extract of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis on Intestinal Flora in ApoE-/- Mice with Atherosclerosis / 中国实验方剂学杂志

ObjectiveTo observe the effect of ethyl acetate extract of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis on high-fat diet-induced apolipoprotein E gene knockout （ApoE-/-） mice， and explore its mechanism of treating atherosclerosis by regulating intestinal flora. MethodThirty-two 8-week-old male ApoE-/- mice were randomly divided into model group， rosuvastatin group （10 mg·kg-1）， high-， low-dose groups of ethyl acetate extract of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis （75， 25 mg·kg-1）， with 8 mice in each group. Eight C57BL/6 mice were used as blank group. After 8 weeks of continuous administration， blood was taken to determine the blood lipid level. Enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of related indexes in serum of mice. Hematoxylin-eosin （HE） staining was used to observe the formation of aortic plaque in mice. Cecal contents were collected and 16S rRNA amplicon sequencing was used to detect intestinal flora. ResultCompared with the blank group， the plaque area of the model group was significantly increased with inflammatory infiltration， the contents of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， inflammatory factors and inducible nitric oxide synthase （iNOS） were increased， while the content of high-density lipoprotein cholesterol （HDL-C） was decreased. Compared with the model group， rosuvastatin group and high- and low-dose groups of ethyl acetate extract of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis could improve the deposition of aortic plaque， reduce the contents of TG， TC， LDL-C， inflammatory factors and iNOS， and increase the content of HDL-C. Compared with the blank group， the relative abundances of Firmicutes and Proteobacteria in the model group increased， while the relative abundance of Bacteroidetes decreased. Alpha and Beta diversity analysis showed that samples of each group could be significantly isolated， and the total number and abundance of intestinal flora species in the model group were low. Compared with the model group， ethyl acetate extract of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis could increase the relative abundance of beneficial bacteria and decrease the relative abundance of pathogenic bacteria. ConclusionEthyl acetate extract of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis was mainly composed of flavonoids， which can treat atherosclerosis by regulating the intestinal flora and improve the pathological changes in the aorta of ApoE-/- mice induced by high-fat diet. The mechanism may be related to its ability to reduce the level of inflammatory factors， improve antioxidant capacity and repair the disorder of intestinal flora structure.

APOE ɛ4 Is Associated with Postprandial Inflammation in Older Adults with Metabolic Syndrome Traits.

The apolipoprotein E (APOE) polymorphism impacts blood lipids and biomarkers of oxidation and inflammation, contributing to an isoform-dependent disease risk. We investigated the effect of the APOE genotype on postprandial metabolism after consumption of three different isoenergetic (4200 kJ) meals in older adults with a CVD risk phenotype. In a randomized crossover study, participants with metabolic syndrome traits (APOE E3, n = 39; E4, n = 10; mean age, 70 ± 5 years; BMI 31.3 ± 3.0 kg/m2) consumed a Western-like diet high-fat (WDHF), Western-like diet high-carbohydrate (WDHC), or Mediterranean-like diet (MED) meal. Parameters of lipid and glucose metabolism, inflammatory, and oxidative parameters were analyzed in blood samples collected at fasting and 1-5 h postprandially. Data were analyzed by linear mixed models. The magnitude of the IL-6 increase after the WDHF meal was significantly higher in E4 than in E3 carriers (iAUC: E4 = 7.76 vs. E3 = 2.81 pg/mL × h). The time to detect the IL-6 increase was shorter in the E4 group. All meals produced postprandial glycemia, insulinemia, and lipidemia, without differences between the E3 and the E4 groups. IL-1ß and oxidized LDL levels did not change postprandially. In conclusion, APOE E4 carriers display increased postprandial inflammation, indicated by higher postprandial IL-6 increase, when compared to non-carriers.

Differential moderation effects of ApoE and 5-HTTLPR genotypes on social vulnerability in predicting mortality among community-dwelling middle-aged and older adults: a nationwide population-based study.

Aging is a dynamic complex process involving social vulnerability over time. The social vulnerability index (SVI) was developed that predicted adverse health outcomes. This study examined effects between SVI status and two genotypes, apolipoprotein E (ApoE) and Serotonin transporter genotyping (5-HTTLPR), on all-cause mortality. Data from the Social Environment and Biomarkers of Aging Study (SEBAS) were obtained, and SVI was constructed using 32 self-reported items of social determinants. Data from 985 participants (age: 65.73 ± 9.47 years, 54.62% males) were obtained for analysis, and the median SVI was 0.35 (IQR 0.29-0.42) with a near normal distribution. Participants with a higher SVI were more likely to be women and have poor cognitive function, more depressive symptoms and poor physical function. Adjusted for age and sex, each incremental deficit in SVI was associated with a 12% increase in mortality risk (HR: 1.12, 95% CI: 1.04-1.20, p = 0.002). An interaction was found between ApoE and SVI but not 5-HTTLPR. The strata-specific hazard ratio confirmed that associations between SVI and mortality was only in non-ε4 carriers (HR: 1.15, 95% CI: 1.07-1.24, p < 0.001), and SVI did not significantly predict mortality among ε4 carriers (HR: 0.84, 95% CI: 0.65-1.10). Differential SVI effects on mortality among middle-age and older adults were identified. In conclusion, a higher SVI was associated with all-cause mortality among middle-aged and older adults, and the association was moderated by ApoE genotypes but not 5-HTTLPR. Further study is needed to evaluate the clinical efficacy of healthy aging intervention programs considering gene-environment interactions and social vulnerability.

Antiviral treatment associated with reduced risk of clinical Alzheimer's disease-A nested case-control study.

INTRODUCTION: In this nested case-control study, we investigated if antiviral treatment given prior to onset of Alzheimer's disease (AD) could influence incident AD. METHODS: From a large population-based cohort study in northern Sweden, 262 individuals that later developed AD were compared to a non-AD matched control group with respect to prescriptions of herpes antiviral treatment. All included subjects were herpes simplex virus 1 (HSV1) carriers and the matching criteria were age, sex, apolipoprotein E genotype (ε4 allele carriership), and study sample start year. RESULTS: Among those who developed AD, 6 prescriptions of antivirals were found, compared to 20 among matched controls. Adjusted for length of follow-up, a conditional logistic regression indicated a difference in the risk for AD development between groups (odds ratio for AD with an antiviral prescription 0.287, P = .018). DISCUSSION: Antiviral treatment might possibly reduce the risk for later development of HSV1-associated AD.

Impact of the Apolipoprotein E ε4 Allele on the Relationship Between Healthy Lifestyle and Cognitive Decline: A Population-Based Study.

Adherence to a healthy lifestyle-characterized by abstaining from smoking, being physically and cognitively active, having a high-quality diet, and limiting alcohol use-is associated with slower cognitive decline in older adults, but whether this relationship extends to persons with a genetic predisposition (e.g., carriers of the ε4 allele of the apolipoprotein E gene (APOE*E4)) remains uncertain. Using data from a population-based study, the Chicago Health and Aging Project (Chicago, Illinois), we followed 3,886 individuals who underwent regular clinical and cognitive assessments from 1993 to 2012. Of 3,886 older adults, 1,269 (32.7%) were APOE*E4 carriers. Compared with noncarriers, APOE*E4 carriers had faster cognitive decline (ß = -0.027 units/year, 95% confidence interval (CI): -0.032, -0.023). In contrast, persons with 2-3 and 4-5 healthy lifestyle factors had slower cognitive decline (ß = 0.008 units/year (95% CI: 0.002, 0.014) and ß = 0.019 units/year (95% CI: 0.011, 0.026), respectively) compared with those with 0-1 factor. In analyses stratified by APOE*E4 status, adherence to a healthy lifestyle (e.g., 4-5 factors vs. 0-1 factors) was associated with a slower rate of cognitive decline in both APOE*E4 carriers (ß = 0.029, 95% CI: 0.013, 0.045) and noncarriers (ß = 0.013, 95% CI: 0.005, 0.022). These results underscore the impact of a healthy lifestyle on cognition, particularly among persons with a genetic predisposition, who are more vulnerable to cognitive decline as they age.

Plasma cholesterol in Alzheimer's disease and frontotemporal dementia.

BACKGROUND: The relationship between the apolipoprotein E (APOE)-ε4 allele, triglyceride (TG) level, and cholesterol level and an increased risk of developing Alzheimer's disease (AD) has been well established, but their relationship with behavioral-variant frontotemporal dementia (bvFTD) is not well-known. METHODOLOGY: The levels of TGs, total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein were measured in bvFTD and AD patients and in normal controls (NCs). DNA was extracted, and APOE was genotyped. RESULTS: The APOE-ε4 allele frequency was higher in the AD group than in the NC group, but no difference was found between the AD and the bvFTD groups. The bvFTD group had higher LDL than the AD group, and significant differences were also found for the cholesterol level in the dementia groups compared with the NC group. Elevated LDL level was positively correlated with appetite and eating score in the bvFTD group. Compared with the AD patients and NCs without the APOE-ε4 allele, those with the APOE-ε4 allele had higher TC, but its correlation with the bvFTD group was absent. CONCLUSIONS: The bvFTD and the AD groups had higher cholesterol levels. The APOE-ε4 allele and eating behavior might modify lipid metabolism in dementia. TG and cholesterol analyses may offer a new opportunity for targeted treatments.

Religiosity and Telomere Length: Moderating Effect of Religiosity on the Relationship Between High-Risk Polymorphisms of the Apolipoprotein E and TOMM40 Gene and Telomere Length.

Objective: The current study seeks to examine the relationship between religiosity and telomere length (TL) in an older Chinese Muslim sample and to explore the moderating effect of religiosity on the relationship between high-risk polymorphisms and TL. Methods: A cross-sectional study of 1,692 community-dwelling adults aged 55 or older was conducted. Apolipoprotein E and TOMM40 (rs2075650) gene polymorphisms and TL were determined using standard procedures. Ordinal logistic regression was used to examine the associations. Results: Religiosity was significantly and positively related to TL. A significant interaction emerged between religiosity and the rs2075650 G polymorphism in predicting TL. Stratified multivariate analyses demonstrated that the relationship between the rs2075650 G state and TL was particularly strong among those who were more religious, as hypothesized. Conclusion: The findings revealed that religiosity may influence cellular aging in part by modifying the effect that high-risk genes have on increasing vulnerability to dementia and cognitive impairment.

The association between the ApoE polymorphisms and the MRI-defined intracranial lesions in a cohort of southern China population.

BACKGROUND: The apolipoprotein E (APOE) ε4 allele is considered as a risk factor for Alzheimer's disease (AD). However, the association of APOE allele with MRI evidence of intracranial lesions has not been well understood. METHODS: Quantitative real-time PCR was performed to detect the APOE genotype; MRI was examined for intracranial lesions. Their association was evaluated in a cohort of 226 AD patients and 2607 healthy individuals in southern China. RESULTS: The frequencies of ε2, ε3, and ε4 alleles were 8.0%, 82.9%, and 9.1% in the whole study population. The frequency of APOE-ε4 allele was significantly higher in the AD subjects than that in the control group (14.4% vs 8.6%, P < 0.001). We found that brain atrophy occurred at a rate of 12.3% in ε4 allele group vs 8.5% in non-ε4 genotype group, with a significance of P = 0.008. Severe brain atrophy occurred at a rate of 1.0% in ε4 allele group vs 0.2% in non-ε4 genotype group (P = 0.011). The individuals carrying APOE ε4/ε4 had an odds ratio (OR) of 7.64 (P < 0.01) for developing AD, while the APOE ε3/ε4 gene carriers had an OR of 1.47 (P = 0.031) and the OR in APOE ε2/ε3 carriers is 0.81 (P = 0.372). Interestingly, we found that the risk of ε4/ε4 allele carrier developing AD was significantly higher in male (P < 0.001) than female (P = 0.478). CONCLUSION: Compared to ε2 and ε3 alleles, the presence of APOE-ε4 allele might increase the risk for AD in a dose-dependent manner in southern China. Moreover, the presence of APOE-ε4 allele results in a higher incidence of brain atrophy.

Apolipoprotein E gene polymorphism and renal function are associated with apolipoprotein E concentration in patients with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) associates with complex lipoprotein disturbances resulting in high cardiovascular risk. Apolipoprotein E (APOE) is a polymorphic protein with three common isoforms (E2; E3; E4) that plays a crucial role in lipoprotein metabolism, including hepatic clearance of chylomicrons and very low-density lipoprotein (VLDL) remnants, and reverse cholesterol transport. It demonstrates anti-atherogenic properties but data concerning the link between polymorphism and level of APOE in CKD patients are inconclusive. The aim of our research was to assess the relationship between APOE gene polymorphism and APOE concentration and its redistribution among lipoproteins along with CKD progression. METHODS: 90 non-dialysed CKD patients were included into the study. Real time PCR was used for APOE genotyping. APOE level was measured in serum and in isolated lipoprotein fractions (VLDL; IDL + HDL; HDL). Kidney function was assessed using eGFR CKD-EPI formula. RESULTS: The population was divided into three APOE genotype subgroups: E2(ε2ε3), E3(ε3ε3) and E4(ε3ε4). The highest APOE level was observed for the E2 subgroup (p < 0.001). APOE concentration positively correlated with eGFR value in the E2 subgroup (r = 0.7, p < 0.001) but inversely in the E3 subgroup (r = - 0.29, p = 0.02).). A lower concentration of APOE in the E2 subgroup was associated with its diminished contents in HDL and IDL + LDL particles. In the E3 subgroup, the higher concentration of APOE was related to the increased number of non-HDL lipoproteins. CONCLUSION: In patients with CKD, APOE genotype as well as renal function are associated with the concentration of APOE and its redistribution among lipoprotein classes.

The Impact of Angiotensin-Converting Enzyme Gene on Behavioral and Psychological Symptoms of Dementia in Alzheimer's Disease.

BACKGROUND: The Angiotensin-Converting Enzyme (ACE) gene has drawn attention for its possible role in regulating the degradation of ß-amyloid (Aß), yet its role in affecting the cognitive and psychiatric symptoms of Alzheimer`s Disease (AD) patients has yet to be elucidated. OBJECTIVE: This study aimed to investigate whether the ACE gene acts as a risk factor of Behavioral and Psychological Symptoms of Dementia (BPSD) in the AD population. METHODS: The genotyping of ACE and Apolipoprotein E gene with allele ε4(APOEε4) was determined among 360s clinically diagnosed AD patients. Symptoms and severity of BPSD were evaluated annually via Neuropsychiatric Inventory (NPI). RESULTS: At the base measurement of the first year of patient recruitment, there were no significant contributory risk factors to NPI score. In the two-year follow-up, ACE insertion polymorphism showed a significant risk (adjusted odds ratio=1.65, 95% CI=1.1- 2.5, p=0.019) of progression of NPI total score. CONCLUSION: ACE gene is involved in aggravating BPSD among AD patients.

Apolipoprotein E (APOE) ε4 genotype is associated with reduced neuropsychological performance in military veterans with a history of mild traumatic brain injury.

INTRODUCTION: The purpose of this study was to investigate the effect of the apolipoprotein E (APOE) ε4 allele on neuropsychological functioning in military Veterans with a remote history of mild traumatic brain injury (mTBI). METHOD: This cross-sectional study included 99 Veterans (mTBI = 53; military controls, MC = 46) who underwent neuropsychological assessment and APOE genotyping. Three neurocognitive composite scores-memory (α = .84), speed (α = .85), and executive functioning (α = .76)-were computed from 24 norm-referenced variables, and the total number of impaired scores (>1.5 SDs below mean) for each participant was calculated. RESULTS: Analyses of covariance adjusting for ethnicity and posttraumatic stress disorder (PTSD) symptoms revealed that although no significant differences were observed between mTBI ε4 allele groups on the executive functioning composite (p > .05), mTBI ε4+ Veterans performed more poorly than ε4- Veterans on the memory (p = .045, ηp2 = .083) and speed (p = .023, ηp2 = .106) composites. Furthermore, Mann-Whitney U tests showed that ε4+ mTBI Veterans displayed a significantly greater number of impaired scores than did ε4- mTBI Veterans (p = .010, r = .355). In contrast, there were no significant differences across any of the cognitive variables between ε4+ and ε4- MCs (all p > .05). CONCLUSIONS: Results suggest that APOE ε4 genotype is related to reduced memory and processingspeed performance, as well as overall cognitive impairment, in those with a history of mTBI, but does not appear to have the same negative effects on cognition in the absence of neurotrauma. Although results are preliminary, the present study advances understanding of genetic influences on cognitive functioning in Veterans with remote mTBIs. Future longitudinal work is needed to elucidate the underlying brain-based mechanisms of ε4 allelic effects on cognitive and clinical outcomes following TBI.

The Association of Apolipoprotein E Gene Polymorphism With Cognitive Performance in Nondemented Polish Adults Aged 55 to 75.

The ε4 allele of the apolipoprotein E (APOE) gene is known as a risk factor for dementia. How APOE ε polymorphism affects cognitive performance in nondemented aging subjects remains less clear. In this study, the relationship between APOE status and cognitive performance across various cognitive domains in adults aged 55 to 75 years ( n = 74) without dementia was investigated. E4 carriers ( n = 11) performed worse versus noncarriers on forward Digit Span and delayed recall of the Rey-Osterrieth complex figure. General linear model analysis revealed a small but significant main effect of ε4 on Rey-Osterrieth complex figure delayed recall. Comparing ε2 carriers, ε3 homozygotes, and ε4 carriers, ε3/ε3 performed significantly better on Trail Making Test part B and derived score Trail Making Test B-A. The findings support the relation between the APOE ε polymorphism and visual memory, short-term auditory memory, visuospatial attention, and executive functions in an aging sample without dementia.