Medicine and Health Sciences Commons^™

Design, Synthesis, And Evaluation Of Novel Positron Emission Tomography Radiotracers, Christopher Philip Surdock

Theses and Dissertations (ETD)

Neuroblastoma (NB) is the most common extracranial tumor in patients under 1 year of age and it constitutes about 8-10% of all childhood cancer. It originates from neural crest cells that normally differentiate to form the sympathetic ganglia, adrenal medulla and other paraspinal sites where sympathetic nervous system tissue is present. Even with an extensive treatment regimen that typically includes surgery, chemotherapy, total body irradiation and autologous stem cell transplantation, the 5-year event-free survival is <50% for high risk patients, and there are numerous long-term side effects associated with treatment. This body of work investigated two projects for improving patient outcomes through the development of positron emission tomography (PET) radiotracers that could be used for therapy planning. The goal of the first project was to design, synthesize, and evaluate PET radiotracers that could measure the enzymatic activation of Irinotecan (CPT-11), a potent chemotherapeutic used in the treatment of colon cancer and several pediatric solid tumors. CPT-11 itself is a prodrug which is converted in vivo to SN-38, via metabolism by carboxylesterase (CE) enzymes. St. Jude Children’s Research Hospital researchers have designed a two-pronged protocol of tumor-targeted CPT-11 chemotherapy combining the complementary approaches of a) specific modulation of human CE in normal tissues to improve drug delivery, and b) tumor-targeted activation of prodrug using neural progenitor cells (NPC) transfected with a mutant human CE cDNA. The tumor-selective trafficking of NPC allows over-expression of CE within the tumor. This prodrug/activating enzyme therapeutic approach has shown extremely encouraging preclinical results in the treatment of NB (90% 1-year survival in mice). However, successful translation of this novel therapeutic approach into general clinical practice requires a better understanding of progenitor cell trafficking, duration and intensity of enzymatic activity and the ultimate biological fate of the therapeutic construct. Toward this end, PET radiotracers were developed based on extensive structure-activity relationship (SAR) studies of CE binding. The goal of the second project was to design, synthesize, and evaluate PET radiotracers that could identify the presence of the tropomyosin receptor kinase B (TrkB). TrkB is not normally found in sympathetic nervous tissue, which is the tissue NB develops from, and thus is a potential target for imaging and therapy. The presence of TrkB and its neurotrophin, brain derived neurotrophic factor (BDNF), have been reported to protect neuroblastoma tumor cells from chemotherapy-induced apoptosis via a phosphatidylinositol 3’-kinase pathway. Radiotracers were synthesized and evaluated for their ability to identify TrkB both in vitro and in vivo. PET radiosynthetic procedures were optimized to synthesize novel radiotracers for imaging targets that could help clinicians monitor therapy or identify markers that would aid in therapy planning for NB patients. The method development could be applied to future compounds that show improved chemical characteristics for synthesis and selectivity.

Translational Pharmacokinetic-Pharmacodynamic Modeling And Simulation In The Development Of Spectinamides, A Novel Class Of Anti-Tuberculosis Agents, Chetan Rathi

Theses and Dissertations (ETD)

New chemotherapeutic agents are urgently needed to control the spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) forms of tuberculosis, which still remains an important public health challenge globally. Recently, spectinamides have emerged as a novel class of anti-tuberculosis agents that overcomethe native drug efflux. Spectinamides bind to the 30S bacterial ribosomal subunit which interferes with ribosomal translocation, and ultimately results in inhibition of protein synthesis. They have potent in vitro activity against drug resistant Mycobacterium tuberculosis (Mtb), and also demonstrated sustained efficacy in (Mtb)-infected mouse models. Pharmacokinetic (PK)/ pharmacodynamic (PD) analyses play a critical role in identifying …

Cannabinoid Receptor 2 (Cb2) Ligands Downregulate Pro-Inflammatory Markers In Stimulated Primary Human Periodontal Ligament Fibroblasts (Hpdlfs), Ammaar Hasan Abidi

Theses and Dissertations (ETD)

There are approximately 743 million individuals suffering from chronic periodontitis (PD) making it the sixth most prevalent condition worldwide. The affected adult population in the U.S. are nearly 64.7 million and the healthcare costs exceeds $14 billion. Recently, host response to pathogenic infection has been seen critical to the progression of PD and exhibit increase in various inflammatory markers. Marijuana is well known for its recreational usage and is a risk factor for periodontal disease, which is seen as a concern in society for its negative health consequences. However, many medical conditions can benefit from the pharmacological effects of cannabinoids. …

Age-Associated Expression Patterns Of Oatp 1b1 And Oatp 1b3 And Their Effect On The Disposition Of Fexofenadine, Margaret Mary Thomson

Theses and Dissertations (ETD)

As part of the drug disposition process (absorption, distribution, metabolism, excretion), an often overlooked aspect is transport. In order for drugs to be metabolized and excreted from the body they go through the liver or other drug removal organs. For drugs that are polar or are large they must rely upon transport mechanisms to transport them across the biomembranes of the drug removal organs. OATP1B1 and OATP1B3 are transporters on the sinusoidal membrane of the liver which work in concert with the drug metabolizing enzymes as part of the drug removal process. It is known that the development of each …

Synthesis Of 20s-Hydroxyvitamin D3 Analogs And Their 1Α-Hydroxyl Derivatives As Potent Anti-Inflammatory Agents, Zongtao Lin

Theses and Dissertations (ETD)

Rheumatoid arthritis (RA) is one of the autoimmune diseases, and is affecting 2.5 million Americans in total. Among the treatment options of RA, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] is the only steroidal drug used clinically for anti-inflammatory and immune diseases. However, long-term use of 1,25(OH)2D3 (625 µg/day) in human would result in hypercalcemia (toxicity), and 1,25(OH)2D3 has substantial hypercalcemic effects (toxicity) in mice at a dose as low as only 2 µg/kg. Fortunately, during the investigation of novel metabolic pathway of vitamin D3 by cytochrome P450 enzymes, we found 20S-hydroxyvitamin D3 [20S(OH)D3] as a good lead compound. 20S(OH)D3 suppressed disease symptoms at …

Biophysical And Biochemical Screening Approaches For Antimicrobial Drug Discovery Targeting S. Aureus Clpp, Aman Preet Singh

Theses and Dissertations (ETD)

The discovery of antibacterial drugs has been among most significant achievements of mankind in saving millions of lives across the planet from infectious diseases. With rise in resistance to almost all existing chemotypes, the design of next generation novel antibiotics has become much more challenging and difficult. The early 21st century witnessed the advancement of multiple novel chemotypes during golden age of antibiotics however the pace of antibiotic drug discovery has slowed down tremendously, contributing to life threatening antimicrobial discovery void since 1980’s. Therefore the need to develop novel antibiotics with unique mechanism of action to leverage against multi drug …

The Development Of Methods To Account For Physiologic Dynamic Changes And Their Effects On The Pharmacokinetics Of Therapeutic Monoclonal Antibodies And Other Therapeutics, Josiah Thomas Ryman

Theses and Dissertations (ETD)

Physiologic changes in the body can drastically affect the clearance of a medication, and therefore increase the variability in exposure to the medication. Physiologic changes that can have a profound effect on the exposure of a medication can stem from changes CYP enzymes, transport proteins, binding protein expression, organ function, immune reactivity, and health status to name a few; with the focus of this dissertation on the dynamic changes in the ontogeny of MRP2 (an apical liver transport protein) and the dynamic changes caused by an immune response to a therapeutic monoclonal antibody (mAb). Several approaches can be used to …

April 2017, Randy Curry, Cindy Brooks

RURAL ROCKS

Rural Rocks, the Rural Health Network newsletter by the SWOSU College of Pharmacy

Perbandingan Efektifitas Antara Minyak Atsiri Kulit Batang Kayu Manis (Cinnamomum Burmannii) Dengan Temephos Sebagai Larvasida Aedes Aegypti, Muhamad Rizki Al Kamal, Neneng Syarifah Syafei, Gita Tiara Dewi Nasution

Pharmaceutical Sciences and Research

Dengue fever is a major health issue in the world. Preventive measure with temephos/abate has long been used to combat this problem. Istiana et al reported that there were cases of resistance of Aedes aegypti larvae to temephos in various parts of the world, including Indonesia. Indonesian Cinnamon (Cinnamomum burmannii) has been proven to possess larvacide effect and can be used as an alternative insecticide. This research was meant to compare the larvacide effect of Indonesian cinnamon (Cinnamomum burmannii) essential oil to the larvacide effect of temephos against Aedes aegypti larvae. This research used laboratory experimental design analysis. The total …

Hubungan Kesesuaian Penulisan Resep Dengan Formulariumnasional Terhadap Mutu Pelayanan Pada Pasien Jaminankesehatan Nasional Di Rumah Sakit Umum Di Bandung, Winda Ratna Pratiwi, Angga Prawira Kautsar, Dolih Gozali

Pharmaceutical Sciences and Research

Pharmaceutical service is one of the activities in hospital that support health service quality. One of the factors that can improve quality of pharmaceutical services is prescription services. In the era of National Health Insurance, prescription given to the patients should be based on the National Formulary. If prescriptions did not suit the national formulary, it would influence the services quality on pharmacy unit. The purposes of this study were to determine suitability of prescription outpatients’ national health insurance with national formulary and to determine the relationship of the suitability of prescription with a national formulary to service quality in …

Kompleks Polielektrolit Kitosan-Xanthan Sebagai Matriks Sediaan Mukoadhesif, Kurnia Sari Setio Putri, Bambang Sulistomo, Silvia Surini

Pharmaceutical Sciences and Research

Mucoadhesive dosage form is a pharmaceutical dosage form with prolonged gastric residence time which can increase bioavailability of drugs. An excipient with suitable swelling and bioadhesive characteristics plays important role to obtain good mucoadhesive dosage form. Our pre-eliminary study showed that chitosan-xanthan gum polyelectrolyte complex (CXPC) in ratio 1:1 exhibit suitable swelling index to be developed as mucoadhesive dosage forms. This research was performed to study CXPC characteristics as matrix for mucoadhesive granules dosage form matrix. In this study CXPC 1:1 was utilized as the matrix in the mucoadhesive granules with drug-CXPC ratio of 1:1, 1:2, and 1:3, using diltiazem …

Skrining Dan Evaluasi Aktivitas Kitinase Dari Sembilan Isolat Bakteri Lokal, Baitha Palanggatan Maggadani, Siswa Setyahadi S, Harmita Harmita

Pharmaceutical Sciences and Research

Chitinase is an enzyme that degrades chitin on β-1,4-acetamido-2-deoxy-D-glycoside bound to produce Chitin oligosaccharide or its soluble monomer, N-acetylglucosamine (NAG). Chitinase are usually produced naturally by chitinolytic microorganism that are found in soil or water environment. Chitinase have been widely used for biocontrol agents of plant pests. The product from chitinase hydrolysis can be used as antiinflammatory agent and anti hyperpigmentation. This research was aimed to screen and evaluate the chitinolytic ability of 9 isolate. The best isolate was the one which produced high chitinolytic activity and hydrolyzed chitin into NAG. 9 isolate were examined and BPPTCC-2 was the best …

Parameter Fisikokimia Dan Analisis Kadar Allyl Disulfidedalam Ekstrak Etanol 70% Bawang Putih (Allium Sativum L.)Dengan Perbandingan Daerah Tempat Tumbuh Parameter, Rini Prastiwi, Siska Siska, Nila Marlita

Pharmaceutical Sciences and Research

Garlic (Allium sativum L.) is one of the medicinal plants that has a potential to be developed to become a traditional medicine. Traditional medicinal products and medicinal plants which have good quality are determined by the quality and safety of the extract. One of many factors that can affect the quality is the growing area. This research aimed to compare the value of physicochemical parameters as well as the levels of compounds responsible for pharmacological activity in ethanol 70% extract of garlic obtained from two growing areas, Bogor and Wonosobo. The test results obtained from garlic extract of Bogor were: …

Practical Use Of Blactchford Score, Shawn E. Fellows, Jamie M. Rosini

Pharmacy Faculty/Staff Publications

Aim: To retrospectively evaluate the use of proton pump inhibitor infusions.

Methods: A retrospective chart review was conducted of all patients who received an 80 mg bolus of esomeprazole follow by an infusion at 8 mg/hr. An analysis was performed to determine if a Blatchford Score of > 5 was a predictor of upper gastrointestinal ulcers.

Results: 300 patients received high dose esomeprazole over a 15 month period. 32% had an ulcer identified on endoscopy. Gastritis and esophagitis were the second most common diagnosis accounting for 16% of patients. A Blatchford Score of >5 as a predictor of upper gastrointestinal ulcers …

Activity Of Distinct Growth Factor Receptor Network Components In Breast Tumors Uncovers Two Biologically Relevant Subtypes, Moom Roosan, Shelley M. Macneil, David F. Jenkins, Gajendra Shrestha, Sydney R. Wyatt, Jasmine A. Mcquerry, Stephen R. Piccolo, Laura M. Heiser, Joe W. Gray, W. Evan Johnson, Andrea H. Bild

Pharmacy Faculty Articles and Research

Background
The growth factor receptor network (GFRN) plays a significant role in driving key oncogenic processes. However, assessment of global GFRN activity is challenging due to complex crosstalk among GFRN components, or pathways, and the inability to study complex signaling networks in patient tumors. Here, pathway-specific genomic signatures were used to interrogate GFRN activity in breast tumors and the consequent phenotypic impact of GRFN activity patterns.

Methods
Novel pathway signatures were generated in human primary mammary epithelial cells by overexpressing key genes from GFRN pathways (HER2, IGF1R, AKT1, EGFR, KRAS (G12V), RAF1, BAD). The pathway analysis toolkit Adaptive Signature Selection …

The Bug-Bag: Consolidating Medications To Cut Costs, James Harrigan, Pharmd, Ms3, Erin Bange, Md, Jessica Caro, Md, Sarah Yeager, Pharmd, David Manoff, Md

College of Pharmacy Posters

Background

Founded in 1991, JeffHOPE is an organization of student run medical clinics providing care to the homeless and underserved populations of Philadelphia. JeffHOPE currently operates at 5 different sites

• Eliza Shirley

Population served: Women and children

Serves as a transitional shelter and aims to help newly homeless women and children find more stable housing

• Sunday Breakfast

Population served: Men older than 18

Serves as a transitional shelter offering housing for 30 days for homeless men

• ACTS

Population served: Women and children

Provides long term housing for women and children who are homeless. The shelter is also located next to …

Nucleic Acid Combinations: A New Frontier For Cancer Treatment, K. C. Remant Bahadur, Bindu Thapa, Juliana Valencia-Serna, Hamidreza Montazeri Aliabadi, Hasan Uludağ

Pharmacy Faculty Articles and Research

The emerging molecular understanding of cancer cell behavior is leading to increasing possibilities to control unchecked cell growth and metastasis. On the other hand, development of multifunctional drug carriers at the ‘nano’-scale is providing exciting new therapeutic strategies in clinical management of cancer beyond the conventional cytotoxic drugs. A new frontier in this regard is the combinational use of complementary agents based on nucleic acids to overcome the limitations of conventional therapy. The existence of tightly-integrated cross-talk through multiple signaling and effector pathways has been appreciated for some time, and the plasticity of such a network to overcome one-dimensional intervention …

Pharmacodynamic Activity Of Fosfomycin Simulating Urinary Concentrations Achieved After A Single 3 Gram Oral Dose Versus Escherichia Coli Using An In Vitro Model, George G. Zhanel, Kate Parkinson, Sean Higgins, Andrew Denisuik, Heather Adam, Johann Pitout, Ayman Noreddin, James A. Karlowsky

Pharmacy Faculty Articles and Research

We assessed the activity of fosfomycin simulating urinary concentrations achieved after a single 3 gram oral dose against Escherichia coli using an in vitro pharmacodynamic model. Eleven urinary isolates of E. coli were studied. Isolates were ESBL-producing or carbapenemase-producing. The in vitro pharmacodynamic model was inoculated with an inoculum of (~1 × 10⁶ cfu/mL). Fosfomycin was administered to simulate maximum free (ƒ) urine (U) concentrations and a t_1/2 obtained after a standard single 3 gram oral dose in healthy volunteers (ƒU_max, 4000 mg/L; t_1/2, 6 h). Sampling was performed over 48 h to assess …

Do You Have Any Questions For The Pharmacist?, Rachel Mays

BU Well

As perhaps the single-most common inquiry in modern healthcare, the question, “Do you have any questions for the pharmacist?” represents not only an integral step in pharmacy workflow, but also an excellent opportunity for healthcare consumer education. Pharmacy counseling serves as arguably the most convenient, accessible avenue for the public to gain medication-related information in an ever-busying and demanding American healthcare culture. Unfortunately, no “one size fits all” approach to pharmacy counseling exists, and delivering meaningful, effective education requires acknowledgement of a variety of patient-specific factors. This article ex­plores the utilization of Myers-Briggs Type Indicator test results to determine impactful …

Crispr: The Last Piece Of The Genetic Puzzle, Brad Broyles

BU Well

CRISPR/Cas9 is an emerging gene editing tool. This technology, which evolved naturally as a defense mechanism for bacteria and other prokaryotes, has been repurposed to edit genes in a wide array of cells, including human cells. This paper outlines the discovery, mechanism, and potential applications of CRISPR/Cas9.

G Protein-Coupled Kiss1 Receptor Is Overexpressed In Triple Negative Breast Cancer And Promotes Drug Resistance., Alexandra Blake, Magdalena Dragan, Rommel G Tirona, Daniel B Hardy, Muriel Brackstone, Alan B Tuck, Andy V Babwah, Moshmi Bhattacharya

Physiology and Pharmacology Publications

Triple-negative breast cancer (TNBC) lacks the expression of estrogen receptor α, progesterone receptor and human epidermal growth factor receptor 2 (HER2). TNBC patients lack targeted therapies, as they fail to respond to endocrine and anti-HER2 therapy. Prognosis for this aggressive cancer subtype is poor and survival is limited due to the development of resistance to available chemotherapies and resultant metastases. The mechanisms regulating tumor resistance are poorly understood. Here we demonstrate that the G protein-coupled kisspeptin receptor (KISS1R) promotes drug resistance in TNBC cells. KISS1R binds kisspeptins, peptide products of the KISS1 gene and in numerous cancers, this signaling pathway …

Chronic Neuropsychological Sequelae In A Patient With Nontumorous Anti-Nmda-Receptor Encephalitis, Dong Y. Han, Lisa M. Mason, Aarti Patel, Zhengqiu Zhou, Sarah Phillips, Siddharth Kapoor

Neurology Faculty Publications

Anti-N-methyl-D-aspartate receptor encephalitis is a neurological, autoimmune disorder tightly conceptualized only as recently as the mid-2000s. It presents itself in a combination of psychiatric, neurological, and autonomic features. We observe a unique case with probable earlier episode (prior to the mid-2000s conceptualization of the disease) and a later relapse, accompanying a comprehensive neuropsychological profile tracked after the relapse and subsequent improvement. Neurocognitive findings revealed residual frontal deficits with mood changes even in the state after plasmapheresis. This case is the first to describe posttreatment cognition in anti-NMDAR encephalitis after probable serial autoimmune episodes.

Swosu Research And Scholarly Activity Fair 2017, Lisa Appeddu, Cj Smith

SWOSU Research and Scholarly Activity Fair Programs

Welcome to the Twenty-Fourth SWOSU Research and Scholarly Activity Fair! On display today are 158 poster presentations and 11 oral presentations, involving 314 student researchers, writers, presenters, and artists, and 47 faculty sponsors encompassing scholarly activity from the SWOSU Departments of Art, Communication, and Theatre; Biological Sciences; Business & Computer Science; Chemistry and Physics; Engineering Technology; Language & Literature; Music; Pharmaceutical Sciences; Psychology; and Social Sciences; and SWOSU School of Nursing and Allied Health Sciences. In addition, there are poster presentations from the Western Technology Center Biomedical Academy, Francis Tuttle Technology Center, El Reno Public Schools, and BlueSTEM AgriLearning …

Cyclosporine Exacerbates Ketamine Toxicity In Zebrafish: Mechanistic Studies On Drug–Drug Interaction, Bonnie L. Robinson, Melanie Dumas, Syed F. Ali, Merle G. Paule, Qiang Gu, Jyotshna Kanungo

United States Food and Drug Administration: Publications

Cyclosporine A (CsA) is an immunosuppressive drug commonly used in organ transplant patients to prevent allograft rejections. Ketamine is a pediatric anesthetic that noncompetitively inhibits the calcium-permeable N-methyl-^_D-aspartic acid receptors. Adverse drug–drug interaction effects between ketamine and CsA have been reported in mammals and humans. However, the mechanism of such drug–drug interaction is unclear. We have previously reported adverse effects of combination drugs, such as verapamil/ketamine and shown the mechanism through intervention by other drugs in zebrafish embryos. Here, we show that ketamine and CsA in combination produce developmental toxicity even leading to lethality in zebrafish larvae …

Targeting The Pd-1 Pathway In Pediatric Solid Tumors And Brain Tumors, Lars M. Wagner, Val R. Adams

Pediatrics Faculty Publications

While remarkable advances have been made in the treatment of pediatric leukemia over the past decades, new therapies are needed for children with advanced solid tumors and high-grade brain tumors who fail standard chemotherapy regimens. Immunotherapy with immune checkpoint inhibitors acting through the programmed cell death-1 (PD-1) pathway has shown efficacy in some chemotherapy-resistant adult cancers, generating interest that these agents may also be helpful to treat certain refractory pediatric malignancies. In this manuscript we review current strategies for targeting the PD-1 pathway, highlighting putative biomarkers and the rationale for investigation of these drugs to treat common pediatric tumors such …

Latanoprost And Timolol In Hydrogel Soft Drug-Dispensing Contact Lenses: A Comparative Analysis, Neha Potdar

Virginias Collegiate Honors Council Conference

Glaucoma patients only can instill glaucoma eye drops. This results in 1-7% absorption of the medication. Surveys show that patients forget to take their medication and have difficulty inserting their eye drops. Researchers at the Massachusetts Eye and Ear Infirmary have developed latanoprost drug-dispensing hydrogel soft contact lenses that dispense the drug to help facilitate the process. However, some glaucoma patients do not respond to latanoprost because they have uveitic glaucoma or do not want to experience latanoprost’s ocular side effects. Patients need an alternative which can be inserted into these contact lenses. Another commonly used glaucoma drug is timolol …

Out In The Cold: Ingredients In Over-The-Counter Cold Medicines Can Wreak Havod On A Trainer's Livelihood And An Owner's Prized Racehorse, Clara Fenger, Tanya Boulmetis, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

No abstract provided.

Quality Of Life And Medication Adherence Of Independently Living Older Adults Enrolled In A Pharmacist-Based Medication Management Program, Christopher Harlow, Catherine Hanna, Lynne Eckmann, Yevgeniya Gokun, Faika Zanjani, Karen Blumenschein, Holly Divine

Pharmacy Practice and Science Faculty Publications

This study sought to understand the medication adherence and quality of life (QOL) of recipients of a pharmacist-based medication management program among independently living older adults. Using a cross-sectional, quasi-experimental study design, we compared older adults enrolled in the program to older adults not enrolled in the program. Data were collected via face-to-face interviews in independent-living facilities and in participants’ homes. Independently living older adults who were enrolled in the medication management program (n = 38) were compared to older adults not enrolled in the program (control group (n = 41)). All participants were asked to complete questionnaires …

Pharmacy Interventions In Transitions Of Care From Hospital Discharge (Pitch) Pilot Program For Medicare Part D Patients At High-Risk For Readmission, Muirisha Nicole Lavender

Doctor of Pharmacy Honors Theses

Background: Pharmacist implemented transitions-of-care (TOC) programs focus on identifying adherence issues, developing care plans, investigating medication-related insurance problems, and instilling the value of medication treatment in patients frequently admitted to hospitals for manageable, chronic disease-states.

Study objective: The primary objective of this study is to determine the impact of pharmacist interventions during a TOC pilot on hospital readmission rates for patients with acute myocardial infarction (AMI), heart failure (HF), chronic obstructive pulmonary disease (COPD), or pneumonia.

Methods: This study is a retrospective review of patients receiving high intensity care to prevent readmission, including pharmacy intervention during a three-month pilot period …

Outcomes After Diagnosis Of Mild Cognitive Impairment In A Large Autopsy Series, Erin L. Abner, Richard J. Kryscio, Frederick A. Schmitt, David W. Fardo, Daniela C. Moga, Eseosa T. Ighodaro, Gregory A. Jicha, Lei Yu, Hiroko H. Dodge, Chengjie Xiong, Randall L. Woltjer, Julie A. Schneider, Nigel J. Cairns, David A. Bennett, Peter T. Nelson

Epidemiology and Environmental Health Faculty Publications

OBJECTIVE: To determine clinical and neuropathological outcomes following a clinical diagnosis of mild cognitive impairment (MCI).

METHODS: Data were drawn from a large autopsy series (N = 1,337) of individuals followed longitudinally from normal or MCI status to death, derived from 4 Alzheimer Disease (AD) Centers in the United States.

RESULTS: Mean follow‐up was 7.9 years. Of the 874 individuals ever diagnosed with MCI, final clinical diagnoses were varied: 39.2% died with an MCI diagnosis, 46.8% with a dementia diagnosis, and 13.9% with a diagnosis of intact cognition. The latter group had pathological features resembling those with a final clinical …