Abstract 117: Apolipoprotein E and use of Statins in Intracerebral Hemorrhage

Background: Apolipoprotein E (ApoE) genotypes have been associated with lobar intracerebral hemorrhage (ICH), and HMG-CoA Reductase Inhibitors (statins) were associated with risk of ICH in a secondary prevention trial. Yet, large meta-analyses of statin use have not consistently identified an increased risk of ICH with statin use. We evaluated whether ApoE genotypes were differentially associated with ICH risk according to statin use. Methods: The Genetic and Environmental Risk Factors for Hemorrhagic Stroke study is a prospective ICH study which recruits cases and controls from the same population. Study physicians adjudicated cases and determined ICH location. Subjects were classified as normocholesterolemia (NC), hypercholesterolemia without statin (HC-NS), and hypercholesterolemia with statin use (HC-S) based on chart review. Genotyping for ApoE ( rs429358 and rs7412) was performed using standard methods. Statistical comparisons were performed using Fisher’s exact test and Mantel-Haenszel tests for homogeneity. Results: From 1997-2008, the study recruited 597 cases of ICH and 1,548 controls. Of these, 26 cases/ 8 controls were excluded for unknown history of hypercholesterolemia, and 13 cases/ 96 controls were excluded for missing ApoE result. Of the 554 cases included, 204 were lobar in location. For non-lobar ICH cases, no significant differences were observed in ApoE genotype and statin use between NC, HC-NS and HC-S cases and controls. However, for lobar ICH, a marked increased risk of ICH was seen in HC-S patients with Apo E4/E4 (OR=4.5; 95% CI 1.3-16; p=0.02) and E2/E4 (OR=11.3; 95%CI 2.0-64; p=0.005), and there was a trend for Apo E2/E3 (OR=2.8; 95% CI 1.1-7.5, p=0.06) compared with Apo E3/E3. Apo E4/E4 did not demonstrate an increased odds of ICH without statin use (OR=1.6; 95% CI 0.27-9.4; p=0.63). The p-value for heterogeneity of odds ratios did not reach statistical significance between the HC-NS vs. HC-S group. Conclusion: Our data support a gene-by-drug effect for lobar ICH and, if confirmed, may indicate a utility for ApoE genotyping to identify patients who would bear the highest risk of ICH with statin use. However, further study is required to determine if an interaction exists or if the finding is associative.

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Micropapillary Thyroid Carcinoma and Hashimoto's Thyroiditis

Otolaryngology ◽

10.1016/j.otohns.2008.05.132 ◽

2008 ◽

Vol 139 (2_suppl) ◽

pp. P40-P40

Author(s):

Michael Navid Pakdaman ◽

Michael P Hier ◽

Martin J Black ◽

Michael Tamilia ◽

Richard J Payne

Keyword(s):

Thyroid Carcinoma ◽

Hashimoto’S Thyroiditis ◽

Statistical Significance ◽

Hashimoto's Thyroiditis ◽

P Value ◽

Exact Test ◽

Increased Risk ◽

Chi Squared ◽

Pathology Reports ◽

The Relationship

Objective An increase in papillary thyroid carcinoma in patients with Hashimoto's thyroiditis has been described. We have yet to find literature discussing a relationship with micropapillary thyroid carcinoma(MPC). Our objective is (1) to assess the relationship between Papillary Microcarcinoma and Hashimoto's Thyroiditis in thyroids without malignant disease, (2) compare effect of the presence of Hashimoto's on prognostic factors in patients. Methods Pathology reports were reviewed for consecutive patients undergoing total thyroidectomy over a 6-year period from 2002 to 2007. Patients with benign pathologies were included. Patients with MPC and no other malignancy were also included. This lead to a cohort of 314 patients. Statistical significance was calculated using Fisher's exact test and a chi-squared analysis. Results Out of the 314 patients, 98 were positive for Hashimoto's thyroiditis on biopsy of the removed thyroid. 58% of the patients with Hashimoto's thyroiditis had an incidental MPC, as compared to 42% of patients where Hashimoto's was not found. Additionally, in Hashimoto patients, 61% of the MPCs were multifocal versus 43% multifocal in the non-Hashimoto group (p-value <0.05 in each comparison). Bilaterality of MPC was also increased in patients with Hashimoto's (22% vs 39%). Conclusions Patients with Hashimoto's thyroiditis in this study had an incidence of MPC of 58%, which is significantly greater than the 42% in those without. Hashimoto's was also associated with an increased risk of bilaterality and multifocality. Studies are needed to further corroborate these findings.

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Influence of brain-derived neurotrophic factor and apolipoprotein E genetic variants on hemispheric and lateral ventricular volume of young healthy adults

Acta Neuropsychiatrica ◽

10.1111/j.1601-5215.2011.00546.x ◽

2011 ◽

Vol 23 (3) ◽

pp. 132-138 ◽

Cited By ~ 6

Author(s):

Christos Sidiropoulos ◽

Kourosh Jafari-Khouzani ◽

Hamid Soltanian-Zadeh ◽

Panayiotis Mitsias ◽

Panagiotis Alexopoulos ◽

...

Keyword(s):

Apolipoprotein E ◽

Neurotrophic Factor ◽

Late Onset ◽

Apoe Genotype ◽

Ventricular Volume ◽

Brain Derived Neurotrophic Factor ◽

Healthy Adults ◽

Ventricular Volumes ◽

Neuronal Processes ◽

Apoe Genotypes

Objective: Brain-derived neurotrophic factor (BDNF) and apolipoprotein E (ApoE) are thought to be implicated in a variety of neuronal processes, including cell growth, resilience to noxious stimuli and synaptic plasticity. A Val to Met substitution at codon 66 in the BDNF protein has been associated with a variety of neuropsychiatric conditions. The ApoE4 allele is considered a risk factor for late-onset Alzheimer's disease, but its effects on young adults are less clear. We sought to investigate the effects of those two polymorphisms on hemispheric and lateral ventricular volumes of young healthy adults.Methods: Hemispheric and lateral ventricular volumes of 144 healthy individuals, aged 19–35 years, were measured using high resolution magnetic resonance imaging and data were correlated with BDNF and ApoE genotypes.Results: There were no correlations between BDNF or ApoE genotype and hemispheric or lateral ventricular volumes.Conclusion: These findings indicate that it is unlikely that either the BDNF Val66Met or ApoE polymorphisms exert any significant effect on hemispheric or lateral ventricular volume. However, confounding epistatic genetic effects as well as relative insensitivity of the volumetric methods used cannot be ruled out. Further imaging analyses are warranted to better define any genetic influence of the BDNF Val6Met and ApoE polymorphism on brain structure of young healthy adults.

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Association between Apolipoprotein E Polymorphism and Clinical Outcome after Ischemic Stroke, Intracerebral Hemorrhage, and Subarachnoid Hemorrhage

Cerebrovascular Diseases ◽

10.1159/000520053 ◽

2021 ◽

pp. 1-10

Author(s):

Wen Pan ◽

Min Zhang ◽

Zhenping Guo ◽

Wenfeng Xiao ◽

Chao You ◽

...

Keyword(s):

Ischemic Stroke ◽

Subarachnoid Hemorrhage ◽

Clinical Outcome ◽

Intracerebral Hemorrhage ◽

Apolipoprotein E ◽

Functional Outcomes ◽

Fixed Effects ◽

Meta Analysis ◽

Fixed Effects Models ◽

Increased Risk

Backgrounds: Previous studies reported inconsistent results regarding associations between apolipoprotein E (APOE) polymorphism and clinical outcomes after ischemic stroke (IS), intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH). Thus, the study was designed to make a systematic review and meta-analysis regarding the association between APOE polymorphism and clinical outcome after IS, ICH, and SAH. Methods: To identify studies eligible for this meta-analysis, we searched for articles published before August 2021 in the databases (PubMed, Web of Science, and Google Scholar). We used STATA 12.0 software to compute hazard ratios (HRs) and their 95% confidence intervals (CIs) regarding APOE polymorphism and clinical outcome after IS, ICH, and SAH. Results: Meta-analysis showed no significant association between APOE polymorphism and functional outcome after IS with fixed effects models (ε4 carrier vs. non-ε4 carrier: HR, 1.00; 95% CI: 0.83–1.21, I2 = 29.4%, p = 0.183; ε2 carrier vs. non-ε2 carrier: HR, 0.92; 95% CI: 0.72–1.16, I2 = 15.6%, p = 0.307). Meta-analysis showed that ICH patients carrying ε4 allele have increased risk of poor outcome in Caucasian population with fixed effects models (ε4 carrier vs. non-ε4 carrier: HR, 1.75; 95% CI: 1.19–2.57, I2 = 0.0%, p = 0.543). Meta-analysis showed no significant association between APOE polymorphism and functional outcomes after SAH with random effects models (ε4 carrier vs. non-ε4 carrier: HR, 1.51; 95% CI: 0.80–2.84, I2 = 57.1%, p = 0.022). Conclusions: In conclusion, the present study demonstrated APOE ε4 carriers show worse functional outcomes after ICH, but not after IS or SAH. More large-scale studies were critical to explore the association between APOE polymorphism and clinical outcome after IS, ICH, and SAH.

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APOE genotype regulates pathology and disease progression in synucleinopathy

Science Translational Medicine ◽

10.1126/scitranslmed.aay3069 ◽

2020 ◽

Vol 12 (529) ◽

pp. eaay3069 ◽

Cited By ~ 17

Author(s):

Albert A. Davis ◽

Casey E. Inman ◽

Zachary M. Wargel ◽

Umber Dube ◽

Brittany M. Freeberg ◽

...

Keyword(s):

Substantia Nigra ◽

Transgenic Mice ◽

Cognitive Decline ◽

Apolipoprotein E ◽

Motor Performance ◽

Apoe Genotype ◽

Amyloid Β ◽

Tau Pathology ◽

Increased Risk ◽

Over Time

Apolipoprotein E (APOE) ε4 genotype is associated with increased risk of dementia in Parkinson’s disease (PD), but the mechanism is not clear, because patients often have a mixture of α-synuclein (αSyn), amyloid-β (Aβ), and tau pathologies. APOE ε4 exacerbates brain Aβ pathology, as well as tau pathology, but it is not clear whether APOE genotype independently regulates αSyn pathology. In this study, we generated A53T αSyn transgenic mice (A53T) on Apoe knockout (A53T/EKO) or human APOE knockin backgrounds (A53T/E2, E3, and E4). At 12 months of age, A53T/E4 mice accumulated higher amounts of brainstem detergent-insoluble phosphorylated αSyn compared to A53T/EKO and A53T/E3; detergent-insoluble αSyn in A53T/E2 mice was undetectable. By immunohistochemistry, A53T/E4 mice displayed a higher burden of phosphorylated αSyn and reactive gliosis compared to A53T/E2 mice. A53T/E2 mice exhibited increased survival and improved motor performance compared to other APOE genotypes. In a complementary model of αSyn spreading, striatal injection of αSyn preformed fibrils induced greater accumulation of αSyn pathology in the substantia nigra of A53T/E4 mice compared to A53T/E2 and A53T/EKO mice. In two separate cohorts of human patients with PD, APOE ε4/ε4 individuals showed the fastest rate of cognitive decline over time. Our results demonstrate that APOE genotype directly regulates αSyn pathology independent of its established effects on Aβ and tau, corroborate the finding that APOE ε4 exacerbates pathology, and suggest that APOE ε2 may protect against αSyn aggregation and neurodegeneration in synucleinopathies.

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Prevalence of microalbuminuria and associated factors among HIV − infected ART naïve patients at Mulago hospital: a cross-sectional study in Uganda

BMC Nephrology ◽

10.1186/s12882-020-02091-2 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Thomas Kiggundu ◽

Robert Kalyesubula ◽

Irene Andia-Biraro ◽

Gyaviira Makanga ◽

Pauline Byakika-Kibwika

Keyword(s):

Antiretroviral Therapy ◽

Cross Sectional Study ◽

Cd4 Count ◽

P Value ◽

Mulago Hospital ◽

Sectional Study ◽

Chi Square ◽

Cross Sectional ◽

Exact Test ◽

Increased Risk

Abstract Background HIV infection affects multiple organs and the kidney is a common target making renal disease, one of the recognized complications. Microalbuminuria represents an early, important marker of kidney damage in several populations including HIV-infected antiretroviral therapy (ART) naïve patients. Early detection of microalbuminuria is critical to slowing down progression to chronic kidney disease (CKD) in HIV-infected patients, however, the burden of microalbuminuria in HIV-infected antiretroviral therapy (ART) naïve patients in Uganda is unclear. Methods A cross-sectional study was conducted in the Mulago Immune suppression syndrome (ISS) clinic among adult HIV − infected ART naïve outpatients. Data on patient demographics, medical history was collected. Physical examination was performed to assess body mass index (BMI) and hypertension. A single spot morning urine sample from each participant was analysed for microalbuminuria using spectrophotometry and colorimetry. Microalbuminuria was defined by a urine albumin creatinine ratio (UACR) 30-299 mg/g and macroalbuminuria by a UACR > 300 mg/g. To assess the factors associated with microalbuminuria, chi-square, Fisher’s exact test, quantile regression and logistic regression were used. Results A total of 185 adult participants were consecutively enrolled with median age and CD4+ counts of 33(IQR = 28–40) years and 428 (IQR = 145–689) cells/μL respectively. The prevalence of microalbuminuria was 18.9% (95% CI, 14–25%). None of the participants had macroalbuminuria. CD4+ count <350cells/μL was associated with increased risk of microalbuminuria (OR: 0.27, 95% CI: 0.12–0.59), P value = 0.001). Diabetes mellitus, hypertension, smoking, alcohol intake were not found to be significantly associated with microalbuminuria. Conclusion Microalbuminuria was highly prevalent in adult HIV − infected ART naive patients especially those with low CD4+ count. There is need to study the effect of ART on microalbuminuria in adult HIV − infected patients.

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Statins and Venous Thromboembolism In Lung Cancer

Blood ◽

10.1182/blood.v116.21.5122.5122 ◽

2010 ◽

Vol 116 (21) ◽

pp. 5122-5122

Author(s):

Moh'd Khushman ◽

Abdel-ghanie Abu-samra ◽

Shatha Farhan ◽

Gordon Jacobsen ◽

Amr Hanbali ◽

...

Keyword(s):

Lung Cancer ◽

Venous Thromboembolism ◽

Cancer Patients ◽

Conflicts Of Interest ◽

Statistical Significance ◽

Lipid Lowering ◽

Coagulation Cascade ◽

Controlled Study ◽

Increased Risk ◽

Statin Use

Abstract Abstract 5122 Background: Dyslipidemia plays a major role in the pathophysiology of atherosclerosis which may also contributed to an increased risk of and thromboembolism from the injury of the vascular endothelium and its activation of platelets, thereafter, the coagulation cascade. It has been well-established that the use of statins in patients with dyslipidemia reduces cardiovascular events and mortality, therefore, improves survival. In addition to a cholesterol-lowering effect, statins exhibit antithrombotic and anti-inflammatory properties that may confer a protective benefit to an increased risk of thromboembolism in cancer patients. Several case-controlled studies reported that cancer patients receiving long-term statins, but not other non-statin lipid lowering treatment, had a lower incidence of venous thromboembolism. Methods: To investigate any protective benefit from statin use in lung cancer patients, we have conducted this retrospective, case-controlled study. Total of 1548 patients with lung cancer were included from the tumor registery at Henry Ford Health System, Detroit, Michigan, between January 1999 and December 2004. The data were extracted from available electronic medical records of these patients. Statistical analyses were performed and stratified for statin users versus non statin users. Results: Out of 1,548 patients, 315 patients (average age was 68, range 46–90) were statin users at the time of their lung cancer diagnosis. The remaining 1233 patients (average age was 65.9, range 29–94) were non- statin users. After stratifying for statin use, 25 of the 315 statin users developed DVT/PE (7.9%), while 100 of the 1233 non-statin users developed DVT/PE (8.1%). This potential benefit from statin use can also be better visualized from comparing the development of DVT/PE between the statin and non-statin groups in a Kaplan-Meier curve for the probability of freedom from DVT/PE across time. Though statistical significance was not reached (log-rank p-value = 0.377), a trend towards a slightly decreased incidence of DVT/PE onset in the patients who receiving statin as the lipid-lowering agent has been observed. Conclusion: Based on our preliminary data, statin use in patients with lung cancer has demonstrated a weak but favorable protective effect on the development of a venous thromboembolism. The nature as a retrospective study and not well-balanced two group of patients (e.g., the average age of statin users were 2 years older than the non-statin users) may limit our results from reaching statistical significance. In addition, some of the patients who had no clear documentation of their home medications had also been categorized as non-statin users in our study. The results from our final data analysis will be presented. Disclosures: No relevant conflicts of interest to declare.

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Influence Of RHCE Variant Genotypes On Anti-e Alloimmunization Risk In SCD Patients

Blood ◽

10.1182/blood.v122.21.2392.2392 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2392-2392 ◽

Cited By ~ 1

Author(s):

Ross M Fasano ◽

Mitchell G Bryski ◽

Philippe Pary ◽

Mohamadou Sene ◽

Naomi L.C. Luban

Keyword(s):

Statistical Significance ◽

Compound Heterozygous ◽

Exact Test ◽

African Patient ◽

Increased Risk ◽

African Immigration ◽

Two Generations ◽

History Of ◽

Clinically Significant ◽

African Patients

Abstract Background A higher incidence of Red Blood Cell (RBC) alloimmunization exists in Sickle Cell Disease (SCD) than in any other multiply transfused population. The majority of the RBC alloantibodies are to Rh (D, C, c, E, e) and K antigens. Transfusing Rh and Kell matched RBCs substantially decreases alloimmunization rates in SCD patients; however clinically significant Rh antibodies with apparent common specificities persist as a result of altered RH alleles in SCD patients. Methods SCD patients with a history of ≥15 transfusions or having RBC alloantibody(ies) were consented and asked to complete an ethnicity survey defining patients as “African” (patient or both parents African-born), African American (parents and patient US-born), or other. RH genotyping was performed on all patients using RH Variant Beadchips (BioArray, Warren NJ). Medical records of patients were retrospectively reviewed and compared to RH genotype and ethnicity to determine the clinical impact of RH variants on alloimmunization. Fisher’s Exact test was used to determine statistical significance of correlations. Results Among 117 SCD patients genotyped, 67 (57.3%) had alloantibodies, with a median of 50 transfusion exposures. RHCE variant haplotype frequencies for (C)ces, ces, ceAR, ceMO and ces(340) were 6.8%, 20.1%, 0.9%, 1.3% and 0.4%, respectively. Twenty-two patients were either homozygous (7), compound-heterozygous (5), or heterozygous for these RHCE variant haplotypes with a conventional RH E allele in-trans (10). Of these, approximately 32% (7/22) formed an anti-e alloantibodies after a median of 6 Rhe+ RBC transfusion exposures compared to 7.3% (7/95) of all other patients (p=0.0048). No anti-e alloantibodies were detected in 15/22 patients within the RHCE variant subgroup after 1436 Rhe+ RBC transfusions (median 66 transfusions/patient), yielding an anti-e alloantibody frequency of 0.45/100 units. Fifty percent (11/22) of patient in the RHCE variant subgroup formed an autoantibody, compared with 24% (19/78) of all other patients (p=0.0345). Approximately 32% (8/25) of the “African” patients were homozygous or compound heterozygous for a variant, as opposed to 10.7% of “Non-African” patients (p=0.0312); only 12.5% (1/8) of African patients with RHCE variant subgroup formed anti-e alloantibodies versus 46% of “Non-African” patients this subgroup (p= NS). Conclusion SCD patients with RHCE variant haplotypes are at increased risk for the formation of clinically significant anti-e alloantibodies, which may be inaccurately identified as autoantibodies in the absence of RH genotyping. This implies that RH genotyping should be either incorporated into the standard RBC phenotype evaluation in all SCD patients, or at least into the evaluation of any SCD patient with an autoantibody that demonstrates “e” specificity. We report similar RHCE variant allele frequencies compared to previously published SCD population studies; however we found a higher prevalence of homozygous and compound heterozygous RHCE variant genotypes in SCD patients less then two generations removed from African immigration. Confounding factors for anti-e alloimmunization risk in SCD patients with RHCE variant genotypes other than antigen disparity exist which may explain why “African” patients within the RHCE variant subgroup demonstrated lower anti-e alloimmunization compared to other patients in this group. Further study is warranted to further characterize the immunogenic potential of high incidence Rh antigens in individuals with RH variants, and the immunogenetic variables that affect alloimmunization overall. Disclosures: Fasano: ApoPharma: Honoraria.

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Statin use and risk of renal cell carcinoma in three prospective cohort studies.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.6_suppl.679 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 679-679

Author(s):

Kathryn M. Wilson ◽

Alejandro Sanchez ◽

Rebecca E. Graff ◽

Sabina Signoretti ◽

Toni K. Choueiri ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Cox Proportional Hazards ◽

Health Study ◽

P Value ◽

Increased Risk ◽

Clear Cell Rcc ◽

Statin Use

679 Background: Evidence on statin use and incidence of renal cell carcinoma (RCC) is mixed. Previous results from the Nurses’ Health Study (NHS) and Health Professionals Follow-up Study (HPFS) found a suggestive protective effect in women but not in men (Liu et al, Cancer 2012). We conducted an updated analysis of statin use and risk of total and fatal RCC in the NHS, HPFS, and NHS 2 cohorts, with more than twice as many cases. Methods: We examined the associations between statin use and risk of RCC from 1990 to 2016 in HPFS (men), 1994 to 2016 in NHS (women), and 1999 to 2015 in NHS 2 (women). Information on statin use was collected every two years. We used Cox proportional hazards models, adjusting for known and suspected risk factors, to estimate hazard ratios (HR) and 95% confidence intervals (CI) for use of statins and risk of total and fatal RCC, RCC by stage at diagnosis, and clear cell RCC. We pooled results across cohorts using a random effects model. Results: We documented 661 cases of RCC (310 in HPFS, 255 in NHS, 96 in NHS 2), of which 132 (20%) were fatal. Of the 661 cases, 458 (69%) were clear cell. The pooled multivariable HR for total RCC was 1.01 (95% CI 0.84-1.21) for current statin use, updated over time. Current use was not associated with risk of fatal, advanced (stage T3 or higher), or localized (stage T1 or T2) disease. There were no associations between duration of statin use and risk of RCC; compared to never users, those with less than four years of total use had an HR of 0.91 (95% CI 0.71-1.18), and those with four or more years of use had an HR of 1.03 (95% CI 0.84-1.27). Among men, statin use was associated with increased risk of clear cell RCC (HR for current use: 1.48, 95% CI 1.04-2.11; HR for 4 or more years of use: 1.58, 95% CI 1.05-2.36). Statins were not associated with risk of clear cell RCC in women (HR for current use: 0.77, 95% CI 0.58-1.03; p-value for heterogeneity across cohorts = 0.02). Conclusions: Overall, statin use was not associated with risk of RCC in three large, prospective cohorts of US women and men. Statin use was associated with increased risk of clear cell RCC among men.

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Interaction of Apolipoprotein E Genotypes, Lifestyle Factors and Future Risk of Dementia-Related Mortality: The Cohort of Norway (CONOR)

Dementia and Geriatric Cognitive Disorders ◽

10.1159/000431218 ◽

2015 ◽

Vol 40 (3-4) ◽

pp. 137-147 ◽

Cited By ~ 9

Author(s):

Bjørn Heine Strand ◽

Tor Atle Rosness ◽

Knut Engedal ◽

Per Magnus ◽

Astrid Liv Mina Bergem ◽

...

Keyword(s):

Risk Factors ◽

Apolipoprotein E ◽

Healthy Lifestyle ◽

Lifestyle Risk Factors ◽

Increased Risk ◽

Apolipoprotein E Genotypes ◽

Lifestyle Risk ◽

Apoe Genotypes ◽

Nested Case Control ◽

Related Mortality

Background/Aims: Our aims were two-fold: firstly, to investigate the association and interaction between apolipoprotein E (ApoE), lifestyle risk factors and dementia-related mortality and, secondly, to examine if using dementia-related mortality yielded comparable risk estimates for the ApoE genotypes as reported in studies using a clinical dementia diagnosis as the end point. Methods: We used a nested case-control study with 561 cases drawn from dementia deaths in the Cohort of Norway (CONOR) and 584 alive controls. Results: ApoE ε4 carriers were at increased risk of dementia-related mortality compared to noncarriers [odds ratio (OR) 2.46, 95% confidence interval (CI) 1.93-3.13], and ε4 homozygotes were at particularly high risk (OR 7.86, 95% CI 3.80-13.8), while the ε2 type was associated with a lower risk. The highest risk of dementia-related mortality was found among ε4 carriers with more lifestyle risk factors (ε4 carriers who were smokers, hypertensive, physically inactive and diabetics) versus ε4 noncarriers without lifestyle risk factors (OR 15.4, 95% CI 4.37-52.4). The increased risk was additive, not multiplicative. Conclusions: Ensuring a healthy lifestyle is important to be able to prevent dementia in populations at large, but especially for ε4 carriers. Using dementia mortality gives comparable results for the ApoE-dementia association as studies using clinical dementia diagnoses.

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Associations between depression, sleep disturbance, and apolipoprotein E in the development of Alzheimer's disease: dementia

International Psychogeriatrics ◽

10.1017/s1041610216000405 ◽

2016 ◽

Vol 28 (9) ◽

pp. 1409-1424 ◽

Cited By ~ 40

Author(s):

Shanna L. Burke ◽

Peter Maramaldi ◽

Tamara Cadet ◽

Walter Kukull

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Apolipoprotein E ◽

Sleep Disturbance ◽

Reference Group ◽

Synergistic Effects ◽

Apoe Genotype ◽

The Elderly ◽

Prodromal Symptom ◽

Apoe Genotypes

ABSTRACTBackground:Alzheimer's disease (AD) is a neurodegenerative brain disease that causes cognitive impairment and dementia. Within the US, AD is the most common form of dementia in the elderly, affecting 1 in 10 people over the age of 65. Sleep disturbance has been called a “public health epidemic” and, like depression, is a prodromal symptom of AD but may also contribute to the risk of developing AD. It was hypothesized that sleep disturbance, depression, and the apolipoprotein E (APOE) genotype increase the likelihood of AD.Methods:Utilizing data from the National Alzheimer's Coordinating Center, information from evaluations of 11,453 cognitively asymptomatic participants was analyzed. Survival analysis was used to explore the independent relationships between depression, sleep disturbance, and APOE genotypes with eventual AD diagnosis. Cox proportional hazard models were utilized to explore the main effects and synergistic effects of psychosocial factors as moderated by APOE genotypes.Results:This study reinforced the association between APOE and AD. The hazard of developing AD was eight times higher for those with recent depression and the Ɛ4 homozygote (HR = 8.15 [3.70–17.95]). Among Ɛ4 carriers with clinician-verified depression, the hazard was ten times that of the reference group (HR = 10.11 [4.43–23.09]). The hazard for Ɛ4 carriers reporting sleep disturbance was almost 7 times greater than the reference group (HR = 6.79 [2.38–19.37]).Conclusion:Findings suggest that sleep disturbance, depression, and APOE Ɛ4 genotype are associated with AD during follow-up evaluations among a group of initially cognitively asymptomatic participants. This study contributes to the literature base exploring an increased hazard or risk of AD due to potential modifiable risk factors as well as genetic biomarkers, such as APOE.

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