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


Analysis of apolipoprotein E genetic polymorphism in a large ethnic Hakka population in southern China.

Genet Mol Biol 2018 Oct-Dec;41(4):742-749. Epub 2018 Nov 29.

Center for Cardiovascular Diseases, Meizhou People's Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, P.R. China.

There is currently no data about the genetic variations of APOE in Hakka population in China. The aim of this study was to analyze the allelic and genotypic frequencies of APOE gene polymorphisms in a large ethnic Hakka population in southern China. The APOE genes of 6,907 subjects were genotyped by the gene chip platform. Read More

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http://www.scielo.br/scielo.php?script=sci_arttext&pid=S
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http://dx.doi.org/10.1590/1678-4685-GMB-2017-0301DOI Listing
November 2018
8 Reads

Longer TOMM40 poly-T variants associated with higher FDDNP-PET medial temporal tau and amyloid binding.

PLoS One 2018 5;13(12):e0208358. Epub 2018 Dec 5.

Department of Psychiatry & Biobehavioral Sciences, Semel Institute for Neuroscience & Human Behavior, David Geffen School of Medicine at UCLA, Los Angeles, United States of America.

Background: The translocase of outer mitochondrial membrane 40 (TOMM40), which lies in linkage disequilibrium with the apolipoprotein E (APOE) gene, has been implicated in Alzheimer's disease (AD). TOMM40 influences AD pathology through mitochondrial neurotoxicity, and the medial temporal lobe (MTL) is the most likely brain region for identifying early manifestations of AD-related morphology changes. While early reports indicated that the longer length poly-T allele of TOMM40 increases risk for AD, these findings have not been consistently replicated in further studies. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0208358PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6281258PMC
December 2018
3 Reads

Apolipoprotein E genotype moderates the association between dietary polyunsaturated fat and brain function: an exploration of cerebral glutamate and cognitive performance.

Nutr Neurosci 2018 Nov 22:1-10. Epub 2018 Nov 22.

a Department of Psychology , The University of Texas at Austin , USA.

Objective: To investigate the effect of Apolipoprotein E (APOE) genotype on the association between dietary polyunsaturated fat (PUFA), cognitive function, and cerebral glutamate.

Methods: A participant sample of 122 middle-aged adults were grouped according to APOE genotype (ϵ4 carrier or ϵ4 non-carrier) and asked to record dietary intake for three consecutive days. All participants also underwent neuropsychological testing and a proton magnetic resonance spectroscopy (H MRS) scan to assess glutamate in the posterior cingulate cortex. Read More

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http://dx.doi.org/10.1080/1028415X.2018.1547857DOI Listing
November 2018
8 Reads

Voltammetric determination of the Alzheimer's disease-related ApoE 4 gene from unamplified genomic DNA extracts by ferrocene-capped gold nanoparticles.

Mikrochim Acta 2018 11 14;185(12):549. Epub 2018 Nov 14.

Department oft of Obstetrics and Gynecology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, 410013, People's Republic of China.

A sensitive method is described for detection of the apoE 4 gene detection which is important for early diagnosis of Alzheimer's disease. It is based on signal amplification by using ferrocene (Fc) capped gold nanoparticles modified with streptavidin. The immobilized oligonucleotide probe captures complementary apoE 4 gene. Read More

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http://dx.doi.org/10.1007/s00604-018-3087-9DOI Listing
November 2018
11 Reads

Genome-wide association study of brain amyloid deposition as measured by Pittsburgh Compound-B (PiB)-PET imaging.

Mol Psychiatry 2018 Oct 25. Epub 2018 Oct 25.

Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA.

Deposition of amyloid plaques in the brain is one of the two main pathological hallmarks of Alzheimer's disease (AD). Amyloid positron emission tomography (PET) is a neuroimaging tool that selectively detects in vivo amyloid deposition in the brain and is a reliable endophenotype for AD that complements cerebrospinal fluid biomarkers with regional information. We measured in vivo amyloid deposition in the brains of ~1000 subjects from three collaborative AD centers and ADNI using C-labeled Pittsburgh Compound-B (PiB)-PET imaging followed by meta-analysis of genome-wide association studies, first to our knowledge for PiB-PET, to identify novel genetic loci for this endophenotype. Read More

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http://www.nature.com/articles/s41380-018-0246-7
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http://dx.doi.org/10.1038/s41380-018-0246-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6219464PMC
October 2018
11 Reads

Female Sex and Alzheimer's Risk: The Menopause Connection.

J Prev Alzheimers Dis 2018 ;5(4):225-230

Lisa Mosconi, PhD, Department of Neurology, Weill Cornell Medicine, 428 East 72nd St, Suite 500, Room 407, New York, NY, 10021; Tel: (212) 746-4624, Email:

Along with advanced age and apolipoprotein E (APOE)-4 genotype, female sex is a major risk factor for developing late-onset Alzheimer's disease (AD). Considering that AD pathology begins decades prior to clinical symptoms, the higher risk in women cannot simply be accounted for by their greater longevity as compared to men. Recent investigation into sex-specific pathophysiological mechanisms behind AD risk has implicated the menopause transition (MT), a midlife neuroendocrine transition state unique to females. Read More

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http://dx.doi.org/10.14283/jpad.2018.34DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198681PMC
January 2018
4 Reads

Role of phosphatidylcholine-DHA in preventing APOE4-associated Alzheimer's disease.

Authors:
Rhonda P Patrick

FASEB J 2019 Feb 5;33(2):1554-1564. Epub 2018 Oct 5.

University of California San Francisco Benioff, Children's Hospital Oakland Research Institute, Oakland, California, USA.

Dietary and supplemental intake of the ω-3 fatty acid docosahexaenoic acid (DHA) reduces risk of Alzheimer's disease (AD) and ameliorates symptoms. The apolipoprotein E ( APOE) 4 allele is the strongest risk factor for sporadic AD, exclusive of age. APOE4 carriers respond well to the DHA present in fish but do not respond as well to dietary supplements. Read More

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http://dx.doi.org/10.1096/fj.201801412RDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338661PMC
February 2019
39 Reads

Influence of and on Behavioral and Cognitive Features of Female Patients Affected by Mild Cognitive Impairment or Alzheimer's Disease.

Front Aging Neurosci 2018 13;10:92. Epub 2018 Apr 13.

Department of Neuroscience, Imaging, and Clinical Science, Università degli Studi G. d'Annunzio Chieti e Pescara, Chieti, Italy.

The risk for Alzheimer's disease (AD) is associated with the presence of the 𝜀4 allele of Apolipoprotein E () gene and, recently, with a novel genetic variant of the gene. This study aimed at evaluating interactions between -𝜀4 and /G variants in the modulation of behavioral and cognitive features of two cohorts of patients suffering from mild cognitive impairment (MCI) or AD. We enrolled a total of 173 female MCI or AD patients (83 MCI; 90 AD). Read More

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http://dx.doi.org/10.3389/fnagi.2018.00092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5932379PMC
April 2018
3 Reads

Targeting of nonlipidated, aggregated apoE with antibodies inhibits amyloid accumulation.

J Clin Invest 2018 May 30;128(5):2144-2155. Epub 2018 Mar 30.

Department of Neurology, Hope Center for Neurological Disorders, Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, Missouri, USA.

The apolipoprotein E E4 allele of the APOE gene is the strongest genetic factor for late-onset Alzheimer disease (LOAD). There is compelling evidence that apoE influences Alzheimer disease (AD) in large part by affecting amyloid β (Aβ) aggregation and clearance; however, the molecular mechanism underlying these findings remains largely unknown. Herein, we tested whether anti-human apoE antibodies can decrease Aβ pathology in mice producing both human Aβ and apoE4, and investigated the mechanism underlying these effects. Read More

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http://dx.doi.org/10.1172/JCI96429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5919821PMC
May 2018
9 Reads
3 Citations
13.210 Impact Factor

The clinical significance of plasma clusterin and Aβ in the longitudinal follow-up of patients with Alzheimer's disease.

Alzheimers Res Ther 2017 Nov 23;9(1):91. Epub 2017 Nov 23.

Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.

Background: Clusterin and beta-amyloid (Aβ) are involved in the pathogenesis of Alzheimer's disease (AD). The clinical significance of plasma clusterin and Aβ in AD progression remains controversial.

Methods: We recruited 322 patients with AD and 88 controls between August 2012 and June 2013. Read More

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http://dx.doi.org/10.1186/s13195-017-0319-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5701424PMC
November 2017
13 Reads

Effects of APOE haplotypes and measures of cardiovascular risk over gender-dependent cognitive and functional changes in one year in Alzheimer's disease.

Int J Neurosci 2018 May 21;128(5):472-476. Epub 2017 Nov 21.

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

Background: Illiteracy, high cerebrovascular risk and copies of APOE-ϵ4 are risk factors for Alzheimer's disease dementia (AD). We aimed to investigate the impacts of gender, education, coronary heart disease (CHD) risk and creatinine clearance variations, body mass index (BMI) and APOE haplotypes over the rates of cognitive and functional decline of AD in one year.

Methods: Consecutive outpatients with late-onset AD were assessed for gender, schooling, BMI and APOE haplotypes, variations in one year of creatinine clearance and Framingham projections of the 10-year absolute CHD risk, and prospective scores of the Mini-Mental State Examination (MMSE), the Clinical Dementia Rating Sum-of-Boxes (CDR-SOB), the Index of Independence in Activities of Daily Living (ADL) and Lawton's Scale for Instrumental Activities of Daily Living (IADL). Read More

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http://dx.doi.org/10.1080/00207454.2017.1396986DOI Listing
May 2018
7 Reads

Apolipoprotein E4, Gender, Body Mass Index, Inflammation, Insulin Resistance, and Air Pollution Interactions: Recipe for Alzheimer's Disease Development in Mexico City Young Females.

J Alzheimers Dis 2017 ;58(3):613-630

Alpert Medical School of Brown University, Providence, RI, USA.

Given the epidemiological trends of increasing Alzheimer's disease (AD) and growing evidence that exposure and lifestyle factors contribute to AD risk and pathogenesis, attention should be paid to variables such as air pollution, in order to reduce rates of cognitive decline and dementia. Exposure to fine particulate matter (PM2.5) and ozone (O3) above the US EPA standards is associated with AD risk. Read More

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http://dx.doi.org/10.3233/JAD-161299DOI Listing
March 2018
61 Reads

Family history and APOE4 risk for Alzheimer's disease impact the neural correlates of episodic memory by early midlife.

Neuroimage Clin 2017 31;14:760-774. Epub 2017 Mar 31.

Brain Imaging Centre, Douglas Mental Health University Institute, Canada.

Episodic memory impairment is a consistent, pronounced deficit in pre-clinical stages of late-onset Alzheimer's disease (AD). Individuals with risk factors for AD exhibit altered brain function several decades prior to the onset of AD-related symptoms. In the current event-related fMRI study of spatial context memory we tested the hypothesis that middle-aged adults (MA; 40-58 yrs) with a family history of late onset AD (MA), or a combined + FH and apolipoprotein E ε4 allele risk factors for AD (MA), will exhibit differences in encoding and retrieval-related brain activity, compared to - FH - APOE4 MA controls. Read More

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http://dx.doi.org/10.1016/j.nicl.2017.03.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385589PMC
April 2017
7 Reads

Increased hippocampal activation in ApoE-4 carriers and non-carriers with amnestic mild cognitive impairment.

Neuroimage Clin 2017 7;13:237-245. Epub 2016 Dec 7.

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States.

Increased fMRI activation in the hippocampus is recognized as a signature characteristic of the amnestic mild cognitive impairment (aMCI) stage of Alzheimer's disease (AD). Previous work has localized this increased activation to the dentate gyrus/CA3 subregion of the hippocampus and showed a correlation with memory impairments in those patients. Increased hippocampal activation has also been reported in carriers of the ApoE-4 allelic variation independently of mild cognitive impairment although these findings were not localized to a hippocampal subregion. Read More

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http://dx.doi.org/10.1016/j.nicl.2016.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5217770PMC
November 2017
12 Reads

Genetic variants associated with risk of Alzheimer's disease contribute to cognitive change in midlife: The Atherosclerosis Risk in Communities Study.

Am J Med Genet B Neuropsychiatr Genet 2017 Apr 26;174(3):269-282. Epub 2016 Oct 26.

Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas.

Alzheimer's disease (AD) is the most common form of dementia and is characterized by impairment in memory, behavioral changes, and gradual loss of autonomy. Since there is a long latent period prior to diagnosis, the aim of this study was to determine whether twenty single nucleotide polymorphisms identified in genome-wide association analyses of AD are associated with cognitive change in 8,320 white and 2,039 African-American middle-aged adults enrolled in the prospective Atherosclerosis Risk in Communities (ARIC) study. Cognition was evaluated using the Delayed Word Recall Test (DWRT; verbal memory), Digit Symbol Substitution Test (DSST; processing speed), and Word Fluency Test (WFT; executive function). Read More

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http://dx.doi.org/10.1002/ajmg.b.32509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5935000PMC
April 2017
26 Reads

Association between Genotype and Change in Physical Function in a Population-Based Swedish Cohort of Older Individuals Followed Over Four Years.

Front Aging Neurosci 2016 4;8:225. Epub 2016 Oct 4.

Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg Mölndal, Sweden.

The association between decline in physical function and age-related conditions, such as reduced cognitive performance and vascular disease, may be explained by genetic influence on shared biological pathways of importance for aging. The apolipoprotein E () gene is well-known for its association with Alzheimer's disease, but has also been related to other disorders of importance for aging. The aim of this study was to investigate possible associations between allele status and physical function in a population-based longitudinal study of older individuals. Read More

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http://dx.doi.org/10.3389/fnagi.2016.00225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5047916PMC
October 2016
24 Reads

Chocolate, Air Pollution and Children's Neuroprotection: What Cognition Tools should be at Hand to Evaluate Interventions?

Front Pharmacol 2016 11;7:232. Epub 2016 Aug 11.

School of Psychology, Georgia Institute of Technology Atlanta, GA, USA.

Millions of children across the world are exposed to multiple sources of indoor and outdoor air pollutants, including high concentrations of fine particulate matter (PM2.5) and ozone (O3). The established link between exposure to PM2. Read More

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http://dx.doi.org/10.3389/fphar.2016.00232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4980563PMC
August 2016
31 Reads

Apolipoprotein E Genotype Affects Size of ApoE Complexes in Cerebrospinal Fluid.

J Neuropathol Exp Neurol 2016 Oct 11;75(10):918-924. Epub 2016 Aug 11.

From the Department of Biology (NMH, MAG); and Department of Neuroscience, Georgetown University (GWR), Washington, District of Columbia

Apolipoprotein E (apoE) is associated with lipoproteins in the cerebrospinal fluid (CSF). APOE4 increases and APOE2 decreases the risk for Alzheimer disease (AD) compared to the risk associated with APOE3 Because apoE4 is less efficient at cholesterol efflux than apoE2 or apoE3 in vitro, we hypothesized that APOE genotype may affect apoE particle size in vivo and that these size differences may be related to AD risk. We used nondenaturing gel electrophoresis to test for differences in the size of apoE complexes in human CSF samples of various APOE genotypes and created profiles of each sample to compare the patterns of apoE distribution. Read More

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http://dx.doi.org/10.1093/jnen/nlw067DOI Listing
October 2016
18 Reads

Interactive and additive influences of Gender, BMI and Apolipoprotein 4 on cognition in children chronically exposed to high concentrations of PM2.5 and ozone. APOE 4 females are at highest risk in Mexico City.

Environ Res 2016 10 2;150:411-422. Epub 2016 Jul 2.

Department of Neuroscience, Carleton University, Ottawa, Ontario, Canada.

Children's air pollution exposures are associated with systemic and brain inflammation and the early hallmarks of Alzheimer's disease (AD). The Apolipoprotein E (APOE) 4 allele is the most prevalent genetic risk for AD, with higher risk for women. We assessed whether gender, BMI, APOE and metabolic variables in healthy children with high exposures to ozone and fine particulate matter (PM2. Read More

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http://dx.doi.org/10.1016/j.envres.2016.06.026DOI Listing
October 2016
10 Reads

A novel CCM2 variant in a family with non-progressive cognitive complaints and cerebral microbleeds.

Am J Med Genet B Neuropsychiatr Genet 2017 Apr 8;174(3):220-226. Epub 2016 Jun 8.

Alzheimer Center, Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.

Lobar cerebral microbleeds are most often sporadic and associated with Alzheimer's disease. The aim of our study was to identify the underlying genetic defect in a family with cognitive complaints and multiple lobar microbleeds and a positive family history for early onset Alzheimer's disease. We performed exome sequencing followed by Sanger sequencing for validation purposes on genomic DNA of three siblings with cognitive complaints, reduced amyloid-beta-42 in CSF and multiple cerebral lobar microbleeds. Read More

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http://dx.doi.org/10.1002/ajmg.b.32468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363380PMC
April 2017
16 Reads

Apolipoprotein E*4 (APOE*4) Genotype Is Associated with Altered Levels of Glutamate Signaling Proteins and Synaptic Coexpression Networks in the Prefrontal Cortex in Mild to Moderate Alzheimer Disease.

Mol Cell Proteomics 2016 07 21;15(7):2252-62. Epub 2016 Apr 21.

¶Cell Biology.

It has been hypothesized that Alzheimer disease (AD) is primarily a disorder of the synapse. However, assessment of the synaptic proteome in AD subjects has been limited to a small number of proteins and often included subjects with end-stage pathology. Protein from prefrontal cortex gray matter of 59 AD subjects with mild to moderate dementia and 12 normal elderly subjects was assayed using targeted mass spectrometry to quantify 191 synaptically expressed proteins. Read More

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http://dx.doi.org/10.1074/mcp.M115.056580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4937502PMC
July 2016
17 Reads

APOE, MAPT, and COMT and Parkinson's Disease Susceptibility and Cognitive Symptom Progression.

J Parkinsons Dis 2016 04;6(2):349-59

Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA, USA.

Background: Cognitive decline is well recognized in Parkinson's disease (PD) and a major concern for patients and caregivers. Apolipoprotein E (APOE), catechol-O-methyl transferase (COMT), and microtubule-associated protein tau (MAPT) are of interest related to their contributions to cognitive decline or dementia in PD.

Objective: Here, we investigate whether APOE, COMT, or MAPT influence the rate of cognitive decline in PD patients. Read More

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http://dx.doi.org/10.3233/JPD-150762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5927361PMC
April 2016
12 Reads

Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer's disease.

Brain 2016 05 8;139(Pt 5):1551-67. Epub 2016 Mar 8.

Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA, USA.

SEE SARAZIN ET AL DOI101093/BRAIN/AWW041 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: The advent of the positron emission tomography tracer (18)F-AV1451 provides the unique opportunity to visualize the regional distribution of tau pathology in the living human brain. In this study, we tested the hypothesis that tau pathology is closely linked to symptomatology and patterns of glucose hypometabolism in Alzheimer's disease, in contrast to the more diffuse distribution of amyloid-β pathology. We included 20 patients meeting criteria for probable Alzheimer's disease dementia or mild cognitive impairment due to Alzheimer's disease, presenting with a variety of clinical phenotypes, and 15 amyloid-β-negative cognitively normal individuals, who underwent (18)F-AV1451 (tau), (11)C-PiB (amyloid-β) and (18)F-FDG (glucose metabolism) positron emission tomography, apolipoprotein E (APOE) genotyping and neuropsychological testing. Read More

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http://dx.doi.org/10.1093/brain/aww027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5006248PMC
May 2016
54 Reads

Apolipoprotein E genotype is not associated with cognitive impairment in older adults with bipolar disorder.

Bipolar Disord 2016 Feb 15;18(1):71-7. Epub 2016 Feb 15.

Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo (USP), São Paulo, SP, Brazil.

Objectives: Cognitive decline is part of the long-term outcome for many individuals with bipolar disorder (BD). The ε4 allele (APOE*4) of apolipoprotein E (APOE) is a well-established risk factor for dementia in Alzheimer's disease (AD). However, its contribution to the risk of cognitive deterioration in BD has not yet been determined. Read More

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http://dx.doi.org/10.1111/bdi.12367DOI Listing
February 2016
9 Reads

Cerebral microbleeds as a biomarker in Alzheimer's disease? A review in the field.

Biomark Med 2016 7;10(1):9-18. Epub 2015 Dec 7.

Department of Neurobiology, Care Sciences & Society, Karolinska Institutet, Stockholm, Sweden. Division of Clinical Geriatrics, Karolinska University Hospital, Stockholm, Sweden.

Cerebral microbleeds (CMBs) are a marker of small vessel disease, increasingly recognized as being of importance in the Alzheimer's disease (AD) process. CMBs influence in AD, and its longitudinal impact on disease progression is however still unknown. CMBs show several associations with AD across studies, are associated with decreased cerebrospinal fluid amyloid levels and are related with the ApoE ϵ4 allele, as well as other imaging manifestations typical for small vessel disease. Read More

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http://dx.doi.org/10.2217/bmm.15.101DOI Listing
September 2016
34 Reads

Cognitive and Psychiatric Disturbances in Parkinsonian Syndromes.

Neurol Clin 2016 Feb;34(1):235-46

Department of Neurology, Louisiana State University Health Sciences Center - Shreveport, 1501 King's Highway, Shreveport, LA 71103, USA.

Parkinsonian syndromes share clinical signs including akinesia/bradykinesia and rigidity, which are consequences of pathology involving dopaminergic substantia nigra neurons. Yet cognitive and psychiatric disturbances are common, even early in the course of disease. Executive dysfunction is often measurable in newly diagnosed Parkinson's disease. Read More

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http://dx.doi.org/10.1016/j.ncl.2015.08.010DOI Listing
February 2016
14 Reads

Apolipoprotein E ϵ4 is positively related to spatial performance but unrelated to hippocampal volume in healthy young adults.

Behav Brain Res 2016 Feb 12;299:11-8. Epub 2015 Nov 12.

Department of Psychology, Uppsala University, Uppsala, Sweden.

The apolipoprotein E (APOE) ϵ4 allele is known to be a major genetic risk factor for Alzheimer's disease (AD). It has been linked to especially episodic memory decline and hippocampal atrophy in both healthy and demented elderly populations. In young adults, ϵ4 carriers have shown better performance in episodic memory compared to non-carriers. Read More

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http://dx.doi.org/10.1016/j.bbr.2015.11.006DOI Listing
February 2016
6 Reads

Murine versus human apolipoprotein E4: differential facilitation of and co-localization in cerebral amyloid angiopathy and amyloid plaques in APP transgenic mouse models.

Acta Neuropathol Commun 2015 Nov 10;3:70. Epub 2015 Nov 10.

Department of Neurology, Hope Center for Neurological Disorders, Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, 63110, USA.

Introduction: Amyloid β (Aβ) accumulates in the extracellular space as diffuse and neuritic plaques in Alzheimer's disease (AD). Aβ also deposits on the walls of arterioles as cerebral amyloid angiopathy (CAA) in most cases of AD and sometimes independently of AD. Apolipoprotein E (apoE) ɛ4 is associated with increases in both Aβ plaques and CAA in humans. Read More

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http://dx.doi.org/10.1186/s40478-015-0250-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4641345PMC
November 2015
33 Reads
1 Citation

SPECTRAL GRAPH THEORY AND GRAPH ENERGY METRICS SHOW EVIDENCE FOR THE ALZHEIMER'S DISEASE DISCONNECTION SYNDROME IN -4 RISK GENE CARRIERS.

Proc IEEE Int Symp Biomed Imaging 2015 Apr;2015:458-461

Imaging Genetics Center, Institute for Neuroimaging & Informatics, University of Southern California.

Our understanding of network breakdown in Alzheimer's disease (AD) is likely to be enhanced through advanced mathematical descriptors. Here, we applied spectral graph theory to provide novel metrics of structural connectivity based on 3-Tesla diffusion weighted images in 42 AD patients and 50 healthy controls. We reconstructed connectivity networks using whole-brain tractography and examined, for the first time here, cortical disconnection based on the graph energy and spectrum. Read More

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http://dx.doi.org/10.1109/ISBI.2015.7163910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4578320PMC
April 2015
16 Reads

Examining the association between Apolipoprotein E (APOE) and self-reported sleep disturbances in non-demented older adults.

Neurosci Lett 2015 Oct 24;606:72-6. Epub 2015 Aug 24.

The Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA.

We aimed to examine the association between Apolipoprotein E (APOE) and sleep disturbances. This is a cross-sectional study, from the Washington Heights-Inwood Community Aging Project (WHICAP). A total of 1944 non-demented older adults took part in the study. Read More

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http://dx.doi.org/10.1016/j.neulet.2015.08.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4598304PMC
October 2015
16 Reads

Prion Disease Induces Alzheimer Disease-Like Neuropathologic Changes.

J Neuropathol Exp Neurol 2015 Sep;74(9):873-88

From the Department of Pathology (Neuropathology) (TT, KB, HS, AG, AO, BD, SJD), Department of Neurology (MG), Memory and Aging Center (MG), and Institute for Neurodegenerative Diseases (SJD), University of California San Francisco, San Francisco, California.

We examined the brains of 266 patients with prion disease (PrionD) and found that 46 patients (17%) had Alzheimer disease (AD)-like changes. To explore potential mechanistic links between PrionD and AD, we exposed human brain aggregates (BrnAggs) to a brain homogenate from a patient with sporadic Creutzfeldt-Jakob disease and found that neurons in human BrnAggs produced many β-amyloid (Aβ; Aβ42) inclusions, whereas uninfected control-exposed human BrnAggs did not. Western blot analysis of 20 pooled Creutzfeldt-Jakob disease-infected BrnAggs verified Aβ42 levels higher than those in controls. Read More

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http://dx.doi.org/10.1097/NEN.0000000000000228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5094352PMC
September 2015
49 Reads

Calcium Channel Blockers, Progression to Dementia, and Effects on Amyloid Beta Peptide Production.

Oxid Med Cell Longev 2015 28;2015:787805. Epub 2015 Jun 28.

Department of Chemistry, University of Kentucky, Lexington, KY 40506, USA ; Sanders-Brown Center on Aging and Alzheimer's Disease Center, University of Kentucky, Lexington, KY 40536, USA.

Previous epidemiologic studies suggest that antihypertensive drugs may be protective against cognitive decline. To determine if subjects enrolled in the University of Kentucky longitudinal aging study who used antihypertensive drugs showed diminished progression to dementia, we used a 3-parameter logistic regression model to compare the rate of progression to dementia for subjects who used any of the five common categories of antihypertensive drugs to those with similar demographic characteristics but who did not use antihypertensives. Regression modeling showed that subjects who used calcium channel blockers (CCBs) but not the other classes of antihypertensives showed a significant decrease in the rate of progression to dementia. Read More

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http://dx.doi.org/10.1155/2015/787805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4499419PMC
April 2016
14 Reads

Methylation analysis of multiple genes in blood DNA of Alzheimer's disease and healthy individuals.

Neurosci Lett 2015 Jul 12;600:143-7. Epub 2015 Jun 12.

Department of Translational Research and New Technologies in Medicine and Surgery, Section of Medical Genetics, University of Pisa, Via Roma 55, Pisa 56126, Italy; Interdepartmental Research Center Nutrafood "Nutraceuticals and Food for Health", University of Pisa, Via del Borghetto 80, Pisa 56124, Italy. Electronic address:

We collected blood DNA from 120 late-onset Alzheimer's disease (AD) patients and 115 healthy matched controls and analysed the methylation levels of genes involved in amyloid-beta peptide production (PSEN1 and BACE1), in DNA methylation (DNMT1, DNMT3A and DNMT3B), and in one-carbon metabolism (MTHFR), searching for correlation with age and gender, with biomarkers of one-carbon metabolism (plasma homocysteine, and serum folate and vitamin B12 levels), and with disease status (being healthy or having AD). We also evaluated the contribution of the APOE ϵ4 allele, the major late-onset AD genetic risk factor, to the studied gene methylation levels. All the genes showed low mean methylation levels (<5%) in both AD and control DNA, no difference between groups, and no correlation with the studied biomarkers, except for MTHFR that showed methylation levels ranging from 5% to 75%, and correlation with circulating biomarkers of one-carbon metabolism. Read More

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http://dx.doi.org/10.1016/j.neulet.2015.06.009DOI Listing
July 2015
5 Reads

Mexico City normal weight children exposed to high concentrations of ambient PM2.5 show high blood leptin and endothelin-1, vitamin D deficiency, and food reward hormone dysregulation versus low pollution controls. Relevance for obesity and Alzheimer disease.

Environ Res 2015 Jul 1;140:579-92. Epub 2015 Jun 1.

College of Sciences, University of Texas at San Antonio, San Antonio, TX, USA.

Millions of Mexico, US and across the world children are overweight and obese. Exposure to fossil-fuel combustion sources increases the risk for obesity and diabetes, while long-term exposure to fine particulate matter (PM2.5) and ozone (O3) above US EPA standards is associated with increased risk of Alzheimer's disease (AD). Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00139351150015
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http://dx.doi.org/10.1016/j.envres.2015.05.012DOI Listing
July 2015
16 Reads

Glucose Dysregulation Interacts With APOE-∊4 to Potentiate Temporoparietal Cortical Thinning.

Am J Alzheimers Dis Other Demen 2016 Feb 24;31(1):76-86. Epub 2015 May 24.

Department of Psychiatry, VA Boston Healthcare System, Boston, MA, USA Department of Psychiatry, Harvard Medical School, Boston, MA, USA.

We examined the interactive effects of apolipoprotein ∊4 (APOE-∊4), a risk factor for Alzheimer's disease (AD), and diabetes risk on cortical thickness among 107 healthy elderly participants; in particular, participants included 27 APOE-∊4+ and 80 APOE-∊4- controls using T1-weighted structural magnetic resonance imaging. Regions of interests included select frontal, temporal, and parietal cortical regions. Among APOE-∊4, glucose abnormalities independently predicted reduced cortical thickness among temporoparietal regions but failed to predict changes for noncarriers. Read More

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http://dx.doi.org/10.1177/1533317515587084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913470PMC
February 2016
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Association of the p22phox polymorphism C242T with the risk of late-onset Alzheimer's disease in a northern Han Chinese population.

Int J Neurosci 2016 17;126(7):637-40. Epub 2015 Aug 17.

a Department of Neurology , Linyi People's Hospital , Linyi , China.

The C242T polymorphism of the CYBA gene that encodes p22phox, a component of nicotinamide adenine dinucleotide phosphate oxidase, has been found to modulate reactive oxygen species (ROS) production. Oxidative stress is thought to play a pivotal role in the pathophysiology of Alzheimer's disease (AD), which is manifested as increased availability of ROS because of an imbalanced redox state. Therefore, the aim of this study was to investigate potential associations of the p22phox C242T polymorphism with the risk of late-onset AD (LOAD) in a northern Han Chinese population. Read More

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http://dx.doi.org/10.3109/00207454.2015.1052877DOI Listing
January 2017
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Monocytic elastase-mediated apolipoprotein-E degradation: Potential involvement of microglial elastase-like proteases in apolipoprotein-E proteolysis in brains with Alzheimers disease.

Biochim Biophys Acta 2015 Aug 6;1854(8):1010-8. Epub 2015 May 6.

Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Nishihama, Yamashiro-cho, Tokushima 770-8514, Japan. Electronic address:

Impaired clearance of soluble Aβ (amyloid-β) promotes Aβ aggregation in brains with Alzheimer's disease (AD), while apolipoprotein-E (ApoE) in microglia mediates Aβ clearance. We studied the protease responsible for ApoE(4) degradation in human peripheral monocyte extracts, which are from the same lineage as microglia. We detected the hydrolytic activity for ApoE(4) in high-salt extracts with 2 M NaCl and found that the activity was inhibited by a serine protease inhibitor and an elastase-specific inhibitor, but not by other protease inhibitors. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S15709639150013
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http://dx.doi.org/10.1016/j.bbapap.2015.04.028DOI Listing
August 2015
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Role of Apolipoprotein E in β-Amyloidogenesis: ISOFORM-SPECIFIC EFFECTS ON PROTOFIBRIL TO FIBRIL CONVERSION OF Aβ IN VITRO AND BRAIN Aβ DEPOSITION IN VIVO.

J Biol Chem 2015 Jun 27;290(24):15163-74. Epub 2015 Apr 27.

From the Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences and the Department of Neuropathology, Graduate School of Medicine, University of Tokyo, Tokyo, 113-0033 Japan and

Human APOE ϵ4 allele is a strong genetic risk factor of Alzheimer disease. Neuropathological and genetic studies suggested that apolipoprotein E4 (apoE4) protein facilitates deposition of amyloid β peptide (Aβ) in the brain, although the mechanism whereby apoE4 increases amyloid aggregates remains elusive. Here we show that injection of Aβ protofibrils induced Aβ deposition in the brain of APP transgenic mice, suggesting that Aβ protofibrils acted as a seed for aggregation and deposition of Aβ in vivo. Read More

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http://dx.doi.org/10.1074/jbc.M114.622209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463458PMC
June 2015
11 Reads

CYP2J2 rs890293 polymorphism is associated with susceptibility to Alzheimer's disease in the Chinese Han population.

Neurosci Lett 2015 Apr 18;593:56-60. Epub 2015 Mar 18.

Department of Pharmacy, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, China. Electronic address:

Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by progressive cognitive dysfunction and memory loss. Increasing evidence indicates that inflammation in the brain is a powerful factor in AD progression. Epoxyeicosatrienoic acids, the biologically active derivatives of arachidonic acid, synthesized by cytochrome P450 (CYP) epoxygenases, have been proven to have powerful anti-inflammatory effects. Read More

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http://dx.doi.org/10.1016/j.neulet.2015.03.024DOI Listing
April 2015
10 Reads

Are the effects of APOE ϵ4 on cognitive function in nonclinical populations age- and gender-dependent?

Neurodegener Dis Manag 2015 ;5(1):37-48

School of Psychology, Sussex University, Brighton, UK.

APOE ϵ4 - one of three possible allelic variants (ϵ2, ϵ3 and ϵ4) of the polymorphic protein APOE - is well characterized in its role as the strongest risk factor (after old age) for sporadic Alzheimer's disease (AD). Perhaps less well known, and certainly less well characterized, is that this ϵ4 variant of the APOE gene also is a significant risk factor for age-related cognitive decline in nonclinical populations. This article considers APOE ϵ4 effects on cognition in people without dementia, the extent to which such effects may depend on age and on gender and other interactive biological systems that change across the lifespan. Read More

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http://dx.doi.org/10.2217/nmt.14.43DOI Listing
January 2016
5 Reads

Traumatic brain injury and late-life dementia.

Handb Clin Neurol 2015 ;128:711-22

Department of Physical Medicine and Rehabilitation; Department of Psychiatry and Behavioral Sciences; Cognitive Neurology and Alzheimer's Disease Center, Northwestern University Medical School and Department of Psychology, Northwestern University, Chicago, IL, USA.

Little is known of the impact of traumatic brain injury (TBI) on outcomes decades later when the effects of the injury interact with the aging brain. Some, but not all, epidemiologic studies have reported an association between TBI and increased risk of Alzheimer's disease (AD) and other neurodegenerative disorders years after the injury. There is evidence that this association has a dose-response pattern such that risk of dementia progressively increases as the number and severity of head injuries increase. Read More

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http://dx.doi.org/10.1016/B978-0-444-63521-1.00044-3DOI Listing
August 2016
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Role of genes GSTM1, GSTT1, and MnSOD in the development of late-onset Alzheimer disease and their relationship with APOE*4.

Neurologia 2016 Oct 24;31(8):535-42. Epub 2014 Dec 24.

Laboratorio de Fisiopatología, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela. Electronic address:

Introduction: Several studies have reported increased oxidation of lipids, proteins and DNA in the brains of patients with Alzheimer disease (AD). Moreover, these patients display differences in the activity and polymorphisms of the genes encoding the enzymes GST (T1, M1) and MnSOD. For these reasons, we designed a study of the variability in GSTT1, GSTM1, and MnSOD genes in healthy and AD groups from a Venezuelan population. Read More

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http://dx.doi.org/10.1016/j.nrl.2014.10.012DOI Listing
October 2016
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Combining serum and urine biomarkers in the early diagnosis of mild cognitive impairment that evolves into Alzheimer's disease in patients with the apolipoprotein E ϵ4 genotype.

Biomarkers 2015 Feb 23;20(1):84-8. Epub 2014 Dec 23.

Geriatric Key Laboratory, Hebei General Hospital , Shijiazhuang, Hebei , China .

Possession of the apolipoprotein E (APOE) ϵ4 genotype is a major predictor of progression to Alzheimer's disease (AD), particularly in patients with mild cognitive impairment (MCI). However, the use of APOE genotyping in the diagnosis of MCI is limited due to its low sensitivity and specificity, which often results in a high false-positive rate. In this study, we found that there was a significant decrease in serum BDNF and notable increase in urine AD7c-NTP in MCI patients who harbored the APOE ϵ4 allele. Read More

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http://dx.doi.org/10.3109/1354750X.2014.994036DOI Listing
February 2015
20 Reads

Framingham Coronary Heart Disease Risk Score Can be Predicted from Structural Brain Images in Elderly Subjects.

Front Aging Neurosci 2014 1;6:300. Epub 2014 Dec 1.

Laboratory of Psychiatric Neuroimaging (LIM 21), Department of Psychiatry, Faculty of Medicine, University of São Paulo , São Paulo , Brazil ; Núcleo de Apoio à Pesquisa em Neurociência Aplicada (NAPNA), University of São Paulo , São Paulo , Brazil ; Department and Institute of Psychiatry, University of São Paulo , São Paulo , Brazil.

Recent literature has presented evidence that cardiovascular risk factors (CVRF) play an important role on cognitive performance in elderly individuals, both those who are asymptomatic and those who suffer from symptoms of neurodegenerative disorders. Findings from studies applying neuroimaging methods have increasingly reinforced such notion. Studies addressing the impact of CVRF on brain anatomy changes have gained increasing importance, as recent papers have reported gray matter loss predominantly in regions traditionally affected in Alzheimer's disease (AD) and vascular dementia in the presence of a high degree of cardiovascular risk. Read More

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http://dx.doi.org/10.3389/fnagi.2014.00300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4249461PMC
December 2014
23 Reads

The MTHFR C677T polymorphism contributes to increased risk of Alzheimer's disease: evidence based on 40 case-control studies.

Neurosci Lett 2015 Jan 5;586:36-42. Epub 2014 Dec 5.

Department of Geriatrics, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China. Electronic address:

The association between methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and Alzheimer's Disease (AD) risk has been widely reported with inconsistent results. We performed an updated meta-analysis of all available studies to clarify this situation. We conducted a comprehensive literature search in PubMed Alzgene, Embase, and Chinese Biomedical Literature database (CBM) for the period up to June 2014. Read More

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http://dx.doi.org/10.1016/j.neulet.2014.11.049DOI Listing
January 2015
33 Reads

The effect of galantamine on brain atrophy rate in subjects with mild cognitive impairment is modified by apolipoprotein E genotype: post-hoc analysis of data from a randomized controlled trial.

Alzheimers Res Ther 2014 21;6(4):47. Epub 2014 Jul 21.

Alzheimer Centre, Department of Neurology, VU University Medical Centre, PO Box 7057, 1007 MB Amsterdam, the Netherlands.

Introduction: The aim of this investigation was to assess the effect of galantamine, an acetylcholinesterase inhibitor and allosteric modulator of nicotinic receptors, on brain atrophy in individuals with mild cognitive impairment (MCI), and to assess effect modification by apolipoprotein E (APOE) genotype.

Methods: We used data from the Galantamine-International-11 (Gal-Int-11) trial, a 24-month, randomized, double blind, placebo-controlled, flexible-dose (16 to 24 mg daily) study in patients with MCI. Brain magnetic resonance imaging (MRI), including a 3-dimensional T1-weighted gradient echo volumetric sequence, was performed at screening and at 24 months. Read More

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http://dx.doi.org/10.1186/alzrt275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255389PMC
December 2014
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Low levels of cerebrospinal fluid complement 3 and factor H predict faster cognitive decline in mild cognitive impairment.

Alzheimers Res Ther 2014 23;6(3):36. Epub 2014 Jun 23.

Department of Pathology, University of Washington School of Medicine, HMC Box 359635, 325 9th Avenue, Seattle, WA 98104, USA.

Introduction: Alzheimer's disease (AD) is characterized by the deposition of tau and amyloid in the brain. Although the core cerebrospinal fluid (CSF) AD biomarkers amyloid β peptide 1-42 (Aβ1-42), total tau (t-tau) and phosphorylated tau 181 (p-tau181) show good diagnostic sensitivity and specificity, additional biomarkers that can aid in preclinical diagnosis or better track disease progression are needed. Activation of the complement system, a pivotal part of inflammation, occurs at very early stages in the AD brain. Read More

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http://alzres.biomedcentral.com/articles/10.1186/alzrt266
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http://dx.doi.org/10.1186/alzrt266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255518PMC
December 2014
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Opposite Neural Trajectories of Apolipoprotein E ϵ4 and ϵ2 Alleles with Aging Associated with Different Risks of Alzheimer's Disease.

Cereb Cortex 2016 Apr 21;26(4):1421-1429. Epub 2014 Oct 21.

Department of Neurology, Affiliated ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, Jiangsu, China.

The apolipoprotein E (APOE) ϵ4 allele is a confirmed genetic risk factor and the APOE ϵ2 allele is a protective factor related to late-onset Alzheimer's disease (AD). Intriguingly, recent studies demonstrated similar brain function alterations between APOE ϵ2 and ϵ4 alleles, despite their opposite susceptibilities to AD. To address this apparent discrepancy, we recruited 129 cognitively normal elderly subjects, including 36 ϵ2 carriers, 44 ϵ3 homozygotes, and 49 ϵ4 carriers. Read More

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http://dx.doi.org/10.1093/cercor/bhu237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4785940PMC
April 2016
17 Reads

Cognitive changes preceding clinical symptom onset of mild cognitive impairment and relationship to ApoE genotype.

Curr Alzheimer Res 2014 ;11(8):773-84

Johns Hopkins School of Medicine - Neurology 1620 McElderry Street Reed Hall West 1 , Baltimore, Maryland 21205 United States.

Background: This study had two goals (1) to evaluate changes in neuropsychological performance among cognitively normal individuals that might precede the onset of clinical symptoms, and (2) to examine the impact of Apolipoprotein E (ApoE) genotype on these changes.

Methods: Longitudinal neuropsychological, clinical assessments and consensus diagnoses were completed prospectively in 268 cognitively normal individuals. The mean duration of follow-up was 9. Read More

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4163954PMC
May 2015
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An updated Alzheimer's disease progression model: incorporating non-linearity, beta regression, and a third-level random effect in NONMEM.

J Pharmacokinet Pharmacodyn 2014 Dec 29;41(6):581-98. Epub 2014 Aug 29.

Pharmatherapeutics Clinical Pharmacology, Pfizer Inc., Cambridge, MA, 02139, USA,

Our objective was to expand our understanding of the predictors of Alzheimer's disease (AD) progression to help design a clinical trial on a novel AD medication. We utilized the Coalition Against Major Diseases AD dataset consisting of control-arm data (both placebo and stable background AD medication) from 15 randomized double-blind clinical trials in mild-to-moderate AD patients (4,495 patients; July 2013). Our ADAS-cog longitudinal model incorporates a beta-regression with between-study, -subject, and -residual variability in NONMEM; it suggests that faster AD progression is associated with younger age and higher number of apolipoprotein E type 4 alleles (APOE*4), after accounting for baseline disease severity. Read More

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http://dx.doi.org/10.1007/s10928-014-9375-zDOI Listing
December 2014
23 Reads