328 results match your criteria Alzheimer's Disease and APOE-4


Astrocytic function is associated with both amyloid-β and tau pathology in non-demented carriers.

Brain Commun 2022 22;4(3):fcac135. Epub 2022 May 22.

Clinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden.

A growing body of evidence suggests that astrocytes play a major role in the pathophysiology of Alzheimer's disease. Given that is primarily expressed in astrocytes, these cells might be an important link between the ε4 allele and the development of Alzheimer's disease pathology. Here, we investigate this hypothesis by measuring myo-inositol, a metabolite involved in astrocytic functions, with magnetic resonance spectroscopy. Read More

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Genome-Wide Association Study of Incident Dementia in a Community-Based Sample of Older Subjects.

J Alzheimers Dis 2022 Jun 9. Epub 2022 Jun 9.

Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.

Background: Alzheimer's disease (AD) is a complex disease influenced by the environment and genetics; however, much of the genetic component remains unaccounted for.

Objective: The purpose of this work was to use genome-wide association analyses to detect genetic associations with incident AD in a sample of older adults aged 75 and above.

Methods: We performed a genome-wide association study (GWAS) on genome-wide genotyped and imputed data (14,072,053 variants) on the Gingko Evaluation of Memory (GEM) study sample consisting of 424 incident dementia (mean age = 84. Read More

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A robust and interpretable machine learning approach using multimodal biological data to predict future pathological tau accumulation.

Nat Commun 2022 04 7;13(1):1887. Epub 2022 Apr 7.

Department of Psychology, University of Cambridge, Cambridge, UK.

The early stages of Alzheimer's disease (AD) involve interactions between multiple pathophysiological processes. Although these processes are well studied, we still lack robust tools to predict individualised trajectories of disease progression. Here, we employ a robust and interpretable machine learning approach to combine multimodal biological data and predict future pathological tau accumulation. Read More

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Association Between Plasma Apolipoprotein M With Alzheimer's Disease: A Cross-Sectional Pilot Study From China.

Front Aging Neurosci 2022 18;14:838223. Epub 2022 Mar 18.

Department of Neurology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.

Background: Recent evidence of genetics and metabonomics indicated a potential role of apolipoprotein M (ApoM) in the pathogenesis of Alzheimer's disease (AD). Here, we aimed to investigate the association between plasma ApoM with AD.

Methods: A multicenter, cross-sectional study recruited patients with AD ( = 67), age- and sex-matched cognitively normal (CN) controls ( = 73). Read More

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Global cognitive trajectory patterns in Alzheimer's disease.

Int Psychogeriatr 2022 Mar 25:1-10. Epub 2022 Mar 25.

Retired, Silver School of Social Work, New York University, New York, NY, USA.

Objectives: The literature on Alzheimer's disease (AD) provides little data about long-term cognitive course trajectories. We identify global cognitive outcome trajectories and associated predictor variables that may inform clinical research and care.

Design: Data derived from the National Alzheimer's Coordinating Center (NACC) Uniform Data Set were used to examine the cognitive course of persons with possible or probable AD, a Mini-Mental State Examination (MMSE) of ≥10, and complete annual assessments for 5 years. Read More

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Correlation of plasma and neuroimaging biomarkers in Alzheimer's disease.

Ann Clin Transl Neurol 2022 05 20;9(5):756-761. Epub 2022 Mar 20.

Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA.

Blood-based phosphorylated tau (Ptau) 181 and 217 biomarkers are sensitive and specific for Alzheimer's disease. In this racial/ethnically diverse cohort study, participants were classified as biomarker positive (Ptau+) or negative (Ptau-) based on Ptau 181 and 217 concentrations and as cognitively impaired (Sym) or unimpaired (Asym). The four groups, Ptau-/Asym, Ptau+/Asym, Ptau-/Sym, and Ptau+/Sym, differed by age, APOE-4 allele frequency, total tau, neurofilament light chain, and cortical thickness measured by MRI. Read More

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APOE Effects on Late Life Cognitive Trajectories in Diverse Racial/Ethnic Groups.

J Int Neuropsychol Soc 2022 Mar 4:1-10. Epub 2022 Mar 4.

Department of Neurology, University of California, Davis, USA.

Objective: This study evaluated: (1) apolipoprotein E (APOE) ϵ4 prevalence among Black, Latino, and White older adults, (2) associations of APOE ϵ4 status with baseline level and change over time of cognitive outcomes across groups, and (3) combined impact of APOE ϵ4 prevalence and magnitude of effect on cognitive decline within each racial/ethnic group.

Method: Participants included 297 White, 138 Latino, and 149 Black individuals from the longitudinal UC Davis Diversity Cohort who had APOE genotyping and ≥2 cognitive assessments. Magnitude of associations of ϵ4 with cognitive baseline and change across racial/ethnic groups was tested with multilevel parallel process longitudinal analyses and multiple group models. Read More

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Challenges at the APOE locus: a robust quality control approach for accurate APOE genotyping.

Alzheimers Res Ther 2022 02 4;14(1):22. Epub 2022 Feb 4.

Department of Neurology and Neurological Sciences - Greicius lab, Stanford University, 290 Jane Stanford Way, Stanford, CA, 94304, USA.

Background: Genetic variants within the APOE locus may modulate Alzheimer's disease (AD) risk independently or in conjunction with APOE*2/3/4 genotypes. Identifying such variants and mechanisms would importantly advance our understanding of APOE pathophysiology and provide critical guidance for AD therapies aimed at APOE. The APOE locus however remains relatively poorly understood in AD, owing to multiple challenges that include its complex linkage structure and uncertainty in APOE*2/3/4 genotype quality. Read More

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February 2022

Mitochondrial DNA and Alzheimer's disease: a first case-control study of the Tunisian population.

Mol Biol Rep 2022 Mar 1;49(3):1687-1700. Epub 2021 Dec 1.

Laboratory of Genetics, Immunology and Human Pathology, Faculty of Science of Tunis, University of Tunis El Manar, 2092, Tunis, Tunisia.

Background: Alzheimer's disease (AD) is the most common neurodegenerative disorder in humans and presents a major health problem throughout the world. The etiology of AD is complex, and many factors are implicated, including mitochondria. Mitochondrial alteration has been proposed as a possible cause of AD. Read More

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Effects of Sex, Age, and Apolipoprotein E Genotype on Brain Ceramides and Sphingosine-1-Phosphate in Alzheimer's Disease and Control Mice.

Front Aging Neurosci 2021 27;13:765252. Epub 2021 Oct 27.

Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, Netherlands.

Apolipoprotein ε4 ()4 is a strong risk factor for the development of Alzheimer's disease (AD) and aberrant sphingolipid levels have been implicated in AD. We tested the hypothesis that the genotype affects brain sphingolipid levels in AD. Seven ceramides and sphingosine-1-phosphate (S1P) were quantified by LC-MSMS in hippocampus, cortex, cerebellum, and plasma of <3 months and >5 months old human and targeted replacement mice with or without the familial AD (FAD) background of both sexes (145 animals). Read More

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October 2021

Apolipoprotein E Genetic Variation and Its Association With Cognitive Function in Rural-Dwelling Older South Africans.

Front Genet 2021 14;12:689756. Epub 2021 Oct 14.

Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

Apolipoprotein E () 𝜀4 allele carrier status is well known for its association with an increased likelihood of developing Alzheimer's disease, but its independent role in cognitive function is unclear. genetic variation is understudied in African populations; hence, this cross-sectional study in a rural South African community examined allele and genotype frequencies, and their associations with cognitive function. Cognitive function was assessed using two different screening methods to produce a total cognition score and four domain-specific cognition scores for verbal episodic memory, executive function, language, and visuospatial ability. Read More

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October 2021

Microglia-specific ApoE knock-out does not alter Alzheimer's disease plaque pathogenesis or gene expression.

Glia 2022 02 13;70(2):287-302. Epub 2021 Oct 13.

Department of Neurobiology and Behavior, University of California, Irvine, California, USA.

Previous studies suggest that microglial-expressed Apolipoprotein E (ApoE) is necessary to shift microglia into a neurodegenerative transcriptional state in Alzheimer's disease (AD) mouse models. On the other hand, elimination of microglia shifts amyloid beta (Aβ) accumulation from parenchymal plaques to cerebral amyloid angiopathy (CAA), mimicking the effects of global APOE*4 knock-in. Here, we specifically knock-out microglial-expressed ApoE while keeping astrocytic-expressed ApoE intact. Read More

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February 2022

Menopause impacts human brain structure, connectivity, energy metabolism, and amyloid-beta deposition.

Sci Rep 2021 06 9;11(1):10867. Epub 2021 Jun 9.

Departments of Pharmacology and Neurology, College of Medicine, University of Arizona, Tucson, AZ, USA.

All women undergo the menopause transition (MT), a neuro-endocrinological process that impacts aging trajectories of multiple organ systems including brain. The MT occurs over time and is characterized by clinically defined stages with specific neurological symptoms. Yet, little is known of how this process impacts the human brain. Read More

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Behavioural effects of the insertion/deletion polymorphism in Alzheimer's disease depend upon stratification according to -ϵ4 carrier status.

Cogn Neuropsychiatry 2021 07 25;26(4):293-305. Epub 2021 May 25.

Department of Neurology and Neurosurgery, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, Brazil.

The inherited risk of late-onset Alzheimer's disease (AD) is genetically determined. We aimed to examine associations of genetic variants of and with age at AD onset and with neuropsychiatric symptoms according to each dementia stage. Consecutive outpatients with AD were assessed for demographic features, Clinical Dementia Rating scores, and the 10-item Neuropsychiatric Inventory, and genotyped for rs7412 and rs429358 ( haplotypes, Real-Time Polymerase Chain Reactions), and the insertion/deletion polymorphism (Polymerase Chain Reactions). Read More

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Glycolytic Metabolism, Brain Resilience, and Alzheimer's Disease.

Front Neurosci 2021 28;15:662242. Epub 2021 Apr 28.

Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, KS, United States.

Alzheimer's disease (AD) is the most common form of age-related dementia. Despite decades of research, the etiology and pathogenesis of AD are not well understood. Brain glucose hypometabolism has long been recognized as a prominent anomaly that occurs in the preclinical stage of AD. Read More

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Influence of Pathogenic and Metabolic Genes on the Pharmacogenetics of Mood Disorders in Alzheimer's Disease.

Pharmaceuticals (Basel) 2021 Apr 15;14(4). Epub 2021 Apr 15.

International Center of Neuroscience and Genomic Medicine, EuroEspes Biomedical Research Center, 15165-Bergondo, Corunna, Spain.

Background: Mood disorders represent a risk factor for dementia and are present in over 60% of cases with Alzheimer's disease (AD). More than 80% variability in drug pharmacokinetics and pharmacodynamics is associated with pharmacogenetics.

Methods: Anxiety and depression symptoms were assessed in 1006 patients with dementia (591 females, 415 males) and the influence of pathogenic (APOE) and metabolic (CYP2D6, CYP2C19, and CYP2C9) gene variants on the therapeutic outcome were analyzed after treatment with a multifactorial regime in a natural setting. Read More

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Mediation analysis for mixture Cox proportional hazards cure models.

Stat Methods Med Res 2021 06 9;30(6):1554-1572. Epub 2021 Apr 9.

Department of Statistics, 26451Chinese University of Hong Kong, Hong Kong.

Mediation analysis aims to decompose a total effect into specific pathways and investigate the underlying causal mechanism. Although existing methods have been developed to conduct mediation analysis in the context of survival models, none of these methods accommodates the existence of a substantial proportion of subjects who never experience the event of interest, even if the follow-up is sufficiently long. In this study, we consider mediation analysis for the mixture of Cox proportional hazards cure models that cope with the cure fraction problem. Read More

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Social Networks and Cerebrospinal Fluid Biomarkers of Alzheimer's Disease Pathology in Cognitively Intact Older Adults: The CABLE Study.

J Alzheimers Dis 2021 ;81(1):263-272

Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.

Background: Although social networks are deemed as moderators of incident Alzheimer's disease (AD), few data are available on the mechanism relevant to AD pathology.

Objective: We aimed to investigate whether social networks affect metabolism of cerebrospinal fluid (CSF) AD biomarkers during early stage and identify modification effects of genetic factor and subjective cognitive decline (SCD).

Methods: We studied participants from the Chinese Alzheimer's disease Biomarker and Lifestyle (CABLE) database who received cognition assessments and CSF amyloid-β (Aβ1-42 and Aβ1-40) and tau proteins (total-tau [T-tau] and phosphorylated-tau [P-tau]) measurements. Read More

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September 2021

KL∗VS heterozygosity reduces brain amyloid in asymptomatic at-risk APOE∗4 carriers.

Neurobiol Aging 2021 05 23;101:123-129. Epub 2021 Jan 23.

Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.

KLOTHO∗VS heterozygosity (KL∗VS) was recently shown to be associated with reduced risk of Alzheimer's disease (AD) in APOE∗4 carriers. Additional studies suggest that KL∗VS protects against amyloid burden in cognitively normal older subjects, but sample sizes were too small to draw definitive conclusions. We performed a well-powered meta-analysis across 5 independent studies, comprising 3581 pre-clinical participants ages 60-80, to investigate whether KL∗VS reduces the risk of having an amyloid-positive positron emission tomography scan. Read More

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Recent Consanguinity and Outbred Autozygosity Are Associated With Increased Risk of Late-Onset Alzheimer's Disease.

Front Genet 2020 29;11:629373. Epub 2021 Jan 29.

Functional Imaging in Neuropsychiatric Disorders (FIND) Lab, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, United States.

Prior work in late-onset Alzheimer's disease (LOAD) has resulted in discrepant findings as to whether recent consanguinity and outbred autozygosity are associated with LOAD risk. In the current study, we tested the association between consanguinity and outbred autozygosity with LOAD in the largest such analysis to date, in which 20 LOAD GWAS datasets were retrieved through public databases. Our analyses were restricted to eight distinct ethnic groups: African-Caribbean, Ashkenazi-Jewish European, European-Caribbean, French-Canadian, Finnish European, North-Western European, South-Eastern European, and Yoruba African for a total of 21,492 unrelated subjects (11,196 LOAD and 10,296 controls). Read More

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January 2021

Mental Component Score (MCS) from Health-Related Quality of Life Predicts Incidence of Dementia in U.S. Males.

J Prev Alzheimers Dis 2021 ;8(2):169-174

Xiuhua Ding, M.D., Ph.D., Department of Public Health, Western Kentucky University, 1906 College Heights Blvd, Bowling Green, KY 42101, USA, Email: phone: 270-745-3618, Fax: 270-745-6950.

Background: The Medical Outcomes Study Questionnaire Short Form 36 health survey (SF-36) measures health-related quality of life (HRQoL) from the individual's point of view and is an indicator of overall health status.

Objective: To examine whether HRQoL shows differential changes over time prior to dementia onset and investigate whether HRQoL predicts incidence of dementia.

Design: Prevention of Alzheimer's Disease (AD) by Vitamin E and Selenium (PREADViSE) trial, which recruited 7,547 non-demented men between 2002 and 2009. Read More

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Semantic intrusion errors as a function of age, amyloid, and volumetric loss: a confirmatory path analysis.

Int Psychogeriatr 2021 Jan 18:1-11. Epub 2021 Jan 18.

Center for Cognitive Neuroscience and Aging, Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USA.

Objective: To examine the direct and indirect effects of age, APOE ϵ4 genotype, amyloid positivity, and volumetric reductions in AD-prone brain regions as it relates to semantic intrusion errors reflecting proactive semantic interference (PSI) and the failure to recover from proactive semantic interference (frPSI) on the Loewenstein-Acevedo Scales of Semantic Interference and Learning (LASSI-L), a cognitive stress test that has been consistently more predictive of preclinical and prodromal Alzheimer's disease (AD) than traditional list-learning tests.

Design: Cross-sectional study.

Setting: 1Florida Alzheimer's Disease Research Center baseline study. Read More

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January 2021

A cross-sectional examination of a family history of Alzheimer's disease and ApoE epsilon 4 on physical fitness, molecular biomarkers, and neurocognitive performance.

Physiol Behav 2021 03 28;230:113268. Epub 2020 Dec 28.

Division of Behavioral Neurology, Department of Neurology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Taiwan; Alzheimer's Disease Research Center, National Cheng Kung University Hospital, Taiwan. Electronic address:

Purpose: The present study examined whether the ɛ4 allele of the apolipoprotein E (ApoE) gene impacts molecular biomarkers and neurocognitive performance among individuals at genetic risk for developing Alzheimer's disease (AD). The correlations between physical fitness and molecular/neurocognitive indices were also explored.

Methods: Fasting blood samples were collected from 162 individuals with a family history of AD (ADFH). Read More

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A Study on PHF-Tau Network Effected by Apolipoprotein E4.

Am J Alzheimers Dis Other Demen 2020 Jan-Dec;35:1533317520971414

School of Information Science and Engineering, Lanzhou University, Lanzhou, People's Republic of China.

Apolipoprotein E 4 Allele (APOE 4) is an important factors in Mild cognitive impairment (MCI) and Alzheimer's disease(AD). It plays a primary role in abnormal modification of aggregated Tau protein-paired helical filaments Tau (PHF-Tau). In this study, 143 subjects with PHF-Tau PET were divided into 2 groups (APOE 4 carriers and noncarriers). Read More

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February 2021

Detection of presymptomatic Alzheimer's disease through breath biomarkers.

Alzheimers Dement (Amst) 2020 14;12(1):e12088. Epub 2020 Oct 14.

Department of Electrical and Computer Engineering Advanced Materials and Microsystems Laboratory Northeastern University Boston Massachusetts USA.

Introduction: Novel sensors were developed to detect exhaled volatile organic compounds to aid in the diagnosis of mild cognitive impairment associated with early stage Alzheimer's disease (AD). The sensors were sensitive to a rat model that combined the human apolipoprotein E (APOE)4 gene with aging and the Western diet.

Methods: Gas sensors fabricated from molecularly imprinted polymer-graphene were engineered to react with alkanes and small fatty acids associated with lipid peroxidation. Read More

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October 2020

Simulating the Effects of Common Comedications and Genotypes on Alzheimer's Cognitive Trajectory Using a Quantitative Systems Pharmacology Approach.

J Alzheimers Dis 2020 ;78(1):413-424

In Silico Biosciences, Lexington, MA, USA.

Background: Many Alzheimer's disease patients in clinical practice are on polypharmacy for treatment of comorbidities.

Objective: While pharmacokinetic interactions between drugs have been relatively well established with corresponding treatment guidelines, many medications and common genotype variants also affect central brain circuits involved in cognitive trajectory, leading to complex pharmacodynamic interactions and a large variability in clinical trials.

Methods: We applied a mechanism-based and ADAS-Cog calibrated Quantitative Systems Pharmacology biophysical model of neuronal circuits relevant for cognition in Alzheimer's disease, to standard-of-care cholinergic therapy with COMTVal158Met, 5-HTTLPR rs25531, and APOE genotypes and with benzodiazepines, antidepressants, and antipsychotics, all together 9,585 combinations. Read More

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September 2021

Allelic Distribution of Genes for Apolipoprotein E and MTHFR in Patients with Alzheimer's Disease and Their Epistatic Interaction.

J Alzheimers Dis 2020 ;77(3):1095-1105

1st Department of Neurology, Faculty of Medicine, Comenius University and University Hospital, Bratislava, Slovakia.

Background: Genetic risk factors play an important role in the pathogenesis of Alzheimer's disease (AD). However, the gene-gene interaction (epistasis) between specific allelic variants is only partially understood.

Objective: In our study, we examined the presence of the ɛ4 allele of apolipoprotein E (APOE) and the presence of C677T and A1298C (rs1801133 and rs1801131) polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with AD and controls. Read More

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September 2021

4 modifies the relationship between infectious burden and poor cognition.

Neurol Genet 2020 Aug 7;6(4):e462. Epub 2020 Jul 7.

Department of Neurology (C.Z., K.S., Y.P.M.), Vagelos College of Physicians and Surgeons, Columbia University, New York, NY; Department of Neurology (C.Z.), Penn State Health Milton S. Hershey Medical Center; Department of Public Health Sciences (C.Z.), Pennsylvania State College of Medicine, Pennsylvania State University, Hershey, PA; Department of Biostatistics (Y.K.C.), Mailman School of Public Health, Columbia University, New York, NY; Departments of Neurology (R.L.S.), Public Health Sciences, and Human Genomics, Miller School of Medicine, University of Miami, Miami, FL; Cognitive Neuroscience Division (Y.S.), Department of Neurology, Vagelos College of Physicians and Surgeons, Taub Institute for Research of Alzheimer's Disease and the Aging Brain, Gertrude H. Sergievsky Center, Columbia University, New York, NY; Department of Neurology (M.S.V.E.), Vagelos College of Physicians and Surgeons; and Department of Epidemiology (M.S.V.E.), Mailman School of Public Health, Columbia University, New York, NY.

Objective: We investigated whether is an effect modifier of the association between infectious burden (IB) and poor cognition in a multiethnic cohort, the Northern Manhattan Study.

Methods: IB was assessed by a quantitative weighted index of exposure to common pathogens associated with vascular risk, infectious burden index (IBI), and by serology for individual infections. Cognition was assessed by completion of the Mini-Mental State Examination at baseline and a full neuropsychological test battery after a median follow-up of approximately 6 years. Read More

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Alzheimer's disease pathology in a community-based sample of older adults without dementia: The MYHAT neuroimaging study.

Brain Imaging Behav 2021 Jun 3;15(3):1355-1363. Epub 2020 Aug 3.

Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.

A true understanding of the distribution and functional correlates of Alzheimer's disease pathology in dementia-free older adults requires a population-based perspective. Here we report initial findings from a sample of 102 cognitively unimpaired participants (average age 77.2 years, 54. Read More

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Education and the moderating roles of age, sex, ethnicity and apolipoprotein epsilon 4 on the risk of cognitive impairment.

Arch Gerontol Geriatr 2020 Nov/Dec;91:104112. Epub 2020 Jul 13.

Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, South Korea.

Background: We examined how the relationship between education and latelife cognitive impairment (defined as a Mini Mental State Examination score below 24) is influenced by age, sex, ethnicity, and Apolipoprotein E epsilon 4 (APOE*4).

Methods: Participants were 30,785 dementia-free individuals aged 55-103 years, from 18 longitudinal cohort studies, with an average follow-up ranging between 2 and 10 years. Pooled hazard ratios were obtained from multilevel parametric survival analyses predicting cognitive impairment (CI) from education and its interactions with baseline age, sex, APOE*4 and ethnicity. Read More

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December 2020