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1. Aerobic Exercise Training-Induced Changes on DNA Methylation in Mild Cognitively Impaired Elderly African Americans: Gene, Exercise, and Memory Study - GEMS-I

Author

Julius S. Ngwa, Evaristus Nwulia, Oyonumo Ntekim, Fikru B. Bedada, Bernard Kwabi-Addo, Sheeba Nadarajah, Steven Johnson, William M. Southerland, John Kwagyan, and Thomas O. Obisesan

Subjects
African Americans, Alzheimer’s disease, CPG Islands, DNA methylation, mild cognitive impairment, VO2max, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

BackgroundDNA methylation at CpG sites is a vital epigenetic modification of the human genome affecting gene expression, and potentially, health outcomes. However, evidence is just budding on the effects of aerobic exercise-induced adaptation on DNA methylation in older mild cognitively impaired (MCI) elderly African American (AAs). Therefore, we examined the effects of a 6-month aerobic exercise-intervention on genome-wide DNA methylation in elderly AA MCI volunteers.DesignElderly AA volunteers confirmed MCI assigned into a 6-month program of aerobic exercise (eleven participants) underwent a 40-min supervised-training 3-times/week and controls (eight participants) performed stretch training. Participants had maximal oxygen consumption (VO2max) test and Genome-wide methylation levels at CpG sites using the Infinium HumanMethylation450 BeadChip assay at baseline and after a 6-month exercise program. We computed false discovery rates (FDR) using Sidak to account for multiplicity of tests and performed quantitative real-time polymerase chain-reaction (qRT-PCR) to confirm the effects of DNA methylations on expression levels of the top 5 genes among the aerobic participants. CpG sites identified from aerobic-exercise participants were similarly analyzed by the stretch group to quantify the effects of exercise-induced methylation changes among the group of stretch participants.ResultsEleven MCI participants (aerobic: 73% females; mean age 72.3 ± 6.6 years) and eight MCI participants (stretch: 75% female; mean age 70.6 ± 6.7 years) completed the training. Aerobic exercise-training was associated with increases in VO2max and with global hypo- and hypermethylation changes. The most notable finding was CpG hypomethylation within the body of the VPS52 gene (P = 5.4 × 10–26), a Golgi-associated protein, involved in intracellular protein trafficking including amyloid precursor protein. qRT-PCR confirmed a nearly twofold increased expression of VPS52. Other top findings with FDR q-value < 10–5, include hypomethylations of SCARB1 (8.8 × 10–25), ARTN (6.1 × 10–25), NR1H2 (2.1 × 10–18) and PPP2R5D (9.8 × 10–18).ConclusionWe conclude that genome-wide DNA methylation patterns is associated with exercise training-induced methylation changes. Identification of methylation changes around genes previously shown to interact with amyloid biology, intracellular protein trafficking, and lipoprotein regulations provide further support to the likely protective effect of exercise in MCI. Future studies in larger samples are needed to confirm our findings.

Published
2022
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2. Exercise modulates APOE expression in brain cortex of female APOE3 and APOE4 targeted replacement mice

Author

Verona E. Mulgrave, Abdulrahman A. Alsayegh, Aida Jaldi, DianneMarie T. Omire-Mayor, Niaya James, Oyonumo Ntekim, Eric Walters, Emanuel O. Akala, and Joanne S. Allard

Subjects
Cellular and Molecular Neuroscience, Endocrinology, Neurology, Endocrine and Autonomic Systems, General Medicine
Abstract

Apolipoprotein E (ApoE) is the main cholesterol carrier of the brain and the ε4 gene variant (APOE4) is the most prevalent genetic risk factor for Alzheimer's disease (AD), increasing risk up to 15-fold. Several studies indicate that APOE4 modulates critical factors for neuronal function, including brain-derived neurotrophic factor (BDNF) and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α). Both proteins show exercise-induced upregulation, which is presumed to mediate many of the beneficial effects of physical activity including improved cognition; however, there is variability in results between individuals potentially in-part due to genetic variations including APOE isoform. This study aimed to determine if the two most prevalent human APOE isoforms influence adaptive responses to exercise-training. Targeted replacement mice, homozygous for either APOE3 or APOE4 were randomized into exercised and sedentary groups. Baseline locomotor function and voluntary wheel-running behavior was reduced in APOE4 mice. Exercised groups were subjected to daily treadmill running for 8 weeks. ApoE protein in brain cortex was significantly increased by exercise in both genotypes. PGC-1α mRNA levels in brain cortex were significantly lower in APOE4 mice, and only tended to increase with exercise in both genotypes. Hippocampal BDNF protein were similar between genotypes and was not significantly modulated by treadmill running. Behavioral and biochemical variations between APOE3 and APOE4 mice likely contribute to the differential risk for neurological and vascular diseases and the exercise-induced increase in ApoE levels suggests an added feature of the potential efficacy of physical activity as a preventative and therapeutic strategy for neurogenerative processes in both genotypes.

Published
2022

3. The Role of Transportation in the Enrollment of Elderly African Americans into Exercise and Memory Study: GEMS Study

Author

Lennox Graham, Julius Ngwa, Oyonumo Ntekim, Oludolapo Ogunlana, Steven Johnson, Sheeba Nadarajah, Thomas V. Fungwe, Jillian Turner, Mara Ramirez Ruiz, Javed Khan, and Thomas O. Obisesan

Subjects
Health (social science), Sociology and Political Science, Health Policy, Anthropology, Public Health, Environmental and Occupational Health
Abstract

Background Understanding the factors driving recruitment and enrollment of African Americans (AA)s in clinical translational research will assure that underrepresented populations benefit from scientific progress and new developments in the diagnosis and treatment of Alzheimer’s disease and related disorders. While transportation is pivotal to volunteers’ ability to participate in research, its contribution to enrollment in exercise studies on AD is yet to be elucidated. Thus, this research focuses on identifying factors that influence the recruitment and enrollment of African Americans in biomedical studies and determining whether the availability of transportation motivates participation in time-demanding exercise studies on AD. Methods We analyzed recruitment data collected from 567 volunteers ages 55 and older screened through various recruitment sources and considered for enrollment in our exercise and memory study. To determine whether transportation influenced the enrollment of African Americans (AA)s in biomedical studies, multiple logistic regression analysis was performed to identify significant factors that drive enrollment. Furthermore, the association of race and demographic factors on the availability of transportation was assessed. Results Demographic factors, age at screening, education, gender, and cognitive scores were not significantly different among those enrolled compared to control (not-enrolled). In the relationship of enrollment to transportation, enrolled participants were more likely to have access to transportation (79.12%) than not-enrolled participants who had less access to transportation (71.6%); however, the association was not statistically significant. However, race differentially influenced the likelihood of enrollment, with elderly AAs being significantly less likely to have transportation (p = 0.020) than the Whites but more likely than “others” to have transportation. Conclusion Our findings suggest that access to transportation may be a key factor motivating enrollment in an exercise and memory study in a predominantly AA sample. Notably, AAs in our sample were less likely to have transportation than Whites. Other demographic factors and cognitive scores did not significantly influence enrollment in our sample. A larger sample and more detailed assessment of transportation are needed to further discern the role of transportation in clinical trials.

Published
2022

4. Exercise Training Induced Changes In Nuclear Magnetic Resonance-Measured Lipid Particles In Mild Cognitively Impaired Elderly African American Volunteers: A Pilot Study

Author

Daniel Larbi, Oludolapo Ogunlana, Oyonumo Ntekim, Joanne S. Allard, Saba Wolday, Thomas O. Obisesan, Steven Johnson, Thomas V. Fungwe, Julius S. Ngwa, Kakra Hughes, Richard F. Gillum, and Sheeba R. Nadarajah

Subjects
Male, medicine.medical_specialty, Magnetic Resonance Spectroscopy, Blood lipids, Pilot Projects, elderly, Lipoprotein particle, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, cardiovascular disease, Internal medicine, medicine, Humans, Aerobic exercise, Cognitive Dysfunction, 030212 general & internal medicine, Cardiovascular fitness, Triglycerides, Original Research, Aged, cardiovascular fitness, exercise, Cholesterol, business.industry, Brain-Derived Neurotrophic Factor, lipoprotein, Cardiorespiratory fitness, General Medicine, Middle Aged, Magnetic Resonance Imaging, 3. Good health, Black or African American, Lipoproteins, LDL, Endocrinology, chemistry, Cardiovascular Diseases, Clinical Interventions in Aging, Female, Geriatrics and Gerontology, business, Alzheimer’s disease, human activities, 030217 neurology & neurosurgery, Chylomicron, Lipoprotein
Abstract

Thomas V Fungwe,1 Julius S Ngwa,2 Oyonumo E Ntekim,1 Joanne S Allard,3 Sheeba Nadarajah,4 Saba Wolday,5 Oludolapo O Ogunlana,5 Steven P Johnson,5 Kakra Hughes,6 Daniel Larbi,5 Richard F Gillum,7 Thomas O Obisesan5 1Department of Nutritional Sciences, School of Nursing and Allied Health Sciences, Howard University, Washington, DC, USA; 2Division of Cardiology, Department of Medicine, Howard University, Washington, DC, USA; 3Division of Cardiology, Department of Physiology and Biophysics, Howard University, Washington, DC, USA; 4Division of Nursing, College of Nursing and Allied Health Sciences, Howard University, Washington, DC, USA; 5Division of Geriatrics, Department of Medicine and Clinical, Howard University Hospital, Washington, DC, USA; 6Department of Surgery, Howard University College of Medicine, Washington, DC, USA; 7Department of Internal Medicine, Howard University Hospital, Washington, DC, USACorrespondence: Thomas O ObisesanDivision of Geriatrics, Department of Medicine and Clinical/Translational Science Program, Howard University Hospital, 2041 Georgia Ave NW, Washington, DC 20060, USATel +1 202 865 3397Fax +1 202 865 3777Email tobisesan@howard.eduPurpose: Poor cardiorespiratory fitness (CRF) is linked to cognitive deterioration, but its effects on lipid heterogeneity and functional properties in older African American (AA) subjects with mild cognitive impairment (MCI) need elucidation. This study determined whether exercise training-induced changes in blood lipid particle sizes (LPS) were associated with CRF determined by VO2Max in elderly AAs with MCI. Given the pivotal role of brain-derived neurotrophic factor (BDNF) on glucose metabolism, and therefore, “diabetic dyslipidemia”, we also determined whether changes in LPS were associated with the levels of serum BDNF.Methods: This analysis included 17 of the 29 randomized elderly AAs with MCI who had NMR data at baseline and after a 6-month training. We used Generalized Linear Regression (GLM) models to examine cardiorespiratory fitness (VO2Max) effects on training-induced change in LPS in the stretch and aerobic groups. Additionally, we determined whether the level of BDNF influenced change in LPS.Results: Collectively, mean VO2Max (23.81±6.17) did not differ significantly between aerobic and stretch groups (difference=3.17±3.56, P=0.495). Training-related changes in very low-density lipoprotein, chylomicrons, and total low-density lipoprotein (LDL) particle sizes correlated significantly with VO2Max, but not after adjustment for age and gender. However, increased VO2Max significantly associated with reduced total LDL particle size after similar adjustments (P = 0.046). While stretch exercise associated with increased protective large high-density lipoprotein particle size, the overall effect was not sustained following adjustments for gender and age. However, changes in serum BDNF were associated with changes in triglyceride and cholesterol transport particle sizes (P < 0.051).Conclusion: Promotion of stretch and aerobic exercise to increase CRF in elderly AA volunteers with MCI may also promote beneficial changes in lipoprotein particle profile. Because high BDNF concentration may reduce CVD risk, training-related improvements in BDNF levels are likely advantageous. Large randomized studies are needed to confirm our observations and to further elucidate the role for exercise therapy in reducing CVD risk in elderly AAs with MCI.Keywords: lipoprotein, elderly, exercise, cardiovascular disease, Alzheimer’s disease, brain-derived neurotrophic factor, cardiovascular fitness

Published
2019
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5. Exercise Training-Increased FBXO32 and FOXO1 in a Gender-Dependent Manner in Mild Cognitively Impaired African Americans: GEMS-1 Study

Author

Fikru B. Bedada, Sheeba R. Nadarajah, Thomas V. Fungwe, Evaristus O. Nwulia, Oyonumo Ntekim, and Thomas O. Obisesan

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Cognitive Neuroscience, ubiquitin proteasome system (UPS), FBXO32/atrogin-1, FOXO1, Disease, lcsh:RC321-571, 03 medical and health sciences, mild cognitive impairment, 0302 clinical medicine, Immune system, immune cells, Internal medicine, Medicine, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Original Research, FBXO32, biology, business.industry, Neurodegeneration, aging, neurodegeneration, medicine.disease, Gait, Ubiquitin ligase, 030104 developmental biology, Proteasome, biology.protein, FoxO transcription factor, cellular clearance system, business, 030217 neurology & neurosurgery, Neuroscience
Abstract

The ubiquitin proteasome system (UPS) and FOXOs transcription factors play a pivotal role in cellular clearance and minimizing the accumulation of Aβ in neurodegeneration (ND). In African Americans (AAs) with mild cognitive impairment (MCI), the role of components of UPS and FOXOs; and whether they are amenable to exercise effects is unknown. We hypothesized that exercise can enhance cellular clearance systems during aging and ND by increasing expressions of FBXO32 and FOXO1. To test this hypothesis, we used TaqMan gene expression analysis in peripheral blood (PB) to investigate the component of UPS and FOXOs; and provide mechanistic insight at baseline, during exercise, and in both genders. At baseline, levels of FBXO32 were higher in women than in men. In our attempt to discern gender-specific exercise-related changes, we observed that levels of FBXO32 increased in men but not in women. Similarly, levels of FOXO1 increased in men only. These data suggest that a graded dose of FBXO32 and FOXO1 may be beneficial when PB cells carrying FBXO32 and FOXO1 summon into the brain in response to Alzheimer’s disease (AD) perturbation (docking station PB cells). Our observation is consistent with emerging studies that exercise allows the trafficking of blood factors. Given the significance of FBXO32 and FOXO1 to ND and associated muscle integrity, our findings may explain, at least in part, the benefits of exercise on memory, associated gait, and balance perturbation acknowledged to herald the emergence of MCI.

Published
2021
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6. Exercise intervention differentially induces the expression of cystathionine beta synthase (CBS) in African American with MCI: Implication for endogenous H 2 S generation and component of aging pathway

Author

Julius S. Ngwa, Steven Johnson, Jillian Turner, Oyonumo Ntekim, Vernon Bond, Thomas O. Obisesan, John Kwagyan, Sheeba R. Nadarajah, and Fikru B. Bedada

Subjects
African american, medicine.medical_specialty, Amyloid, biology, Exercise intervention, Epidemiology, business.industry, Health Policy, Endogeny, Neuropathology, Cystathionine beta synthase, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Endocrinology, Developmental Neuroscience, Internal medicine, medicine, biology.protein, Neurology (clinical), Geriatrics and Gerontology, business
Published
2020
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7. The genetic architecture of the human cerebral cortex

Author

Grasby, Katrina L, Jahanshad, Neda, Shatokhina, Natalia, Mirza-Schreiber, Nazanin, Moreira, Jose C V, Mühleisen, Thomas W, Müller-Myhsok, Bertram, Najt, Pablo, Nakahara, Soichiro, Nho, Kwangsik, Olde Loohuis, Loes M, Orfanos, Dimitri Papadopoulos, Pearson, John F, Zsembik, Leo C P, Pitcher, Toni L, Pütz, Benno, Quidé, Yann, Ragothaman, Anjanibhargavi, Rashid, Faisal M, Reay, William R, Redlich, Ronny, Reinbold, Céline S, Repple, Jonathan, Richard, Geneviève, Thomopoulos, Sophia I, Riedel, Brandalyn C, Risacher, Shannon L, Rocha, Cristiane S, Mota, Nina Roth, Salminen, Lauren, Saremi, Arvin, Saykin, Andrew J, Schlag, Fenja, Schmaal, Lianne, Schofield, Peter R, Zhu, Alyssa H, Secolin, Rodrigo, Shapland, Chin Yang, Shen, Li, Shin, Jean, Shumskaya, Elena, Sønderby, Ida E, Sprooten, Emma, Tansey, Katherine E, Teumer, Alexander, Thalamuthu, Anbupalam, Strike, Lachlan T, Tordesillas-Gutiérrez, Diana, Turner, Jessica A, Uhlmann, Anne, Vallerga, Costanza Ludovica, van der Meer, Dennis, van Donkelaar, Marjolein M J, van Eijk, Liza, van Erp, Theo G M, van Haren, Neeltje E M, van Rooij, Daan, Agartz, Ingrid, van Tol, Marie-José, Veldink, Jan H, Verhoef, Ellen, Walton, Esther, Wang, Mingyuan, Wang, Yunpeng, Wardlaw, Joanna M, Wen, Wei, Westlye, Lars T, Whelan, Christopher D, Alhusaini, Saud, Witt, Stephanie H, Wittfeld, Katharina, Wolf, Christiane, Wolfers, Thomas, Wu, Jing Qin, Yasuda, Clarissa L, Zaremba, Dario, Zhang, Zuo, Zwiers, Marcel P, Artiges, Eric, Almeida, Marcio A A, Assareh, Amelia A, Ayesa-Arriola, Rosa, Belger, Aysenil, Brandt, Christine L, Brown, Gregory G, Cichon, Sven, Curran, Joanne E, Davies, Gareth E, Degenhardt, Franziska, Dennis, Michelle F, Alnæs, Dag, Dietsche, Bruno, Djurovic, Srdjan, Doherty, Colin P, Espiritu, Ryan, Garijo, Daniel, Gil, Yolanda, Gowland, Penny A, Green, Robert C, Häusler, Alexander N, Heindel, Walter, Amlien, Inge K, Ho, Beng-Choon, Hoffmann, Wolfgang U, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Jack, Clifford R, Jang, MiHyun, Jansen, Andreas, Kimbrel, Nathan A, Kolskår, Knut, Painter, Jodie N, Andersson, Micael, Koops, Sanne, Krug, Axel, Lim, Kelvin O, Luykx, Jurjen J, Mathalon, Daniel H, Mather, Karen A, Mattay, Venkata S, Matthews, Sarah, Mayoral Van Son, Jaqueline, McEwen, Sarah C, Ard, Tyler, Melle, Ingrid, Morris, Derek W, Mueller, Bryon A, Nauck, Matthias, Nordvik, Jan E, Nöthen, Markus M, O'Leary, Daniel S, Opel, Nils, Martinot, Marie-Laure Paillère, Pike, G Bruce, Armstrong, Nicola J, Preda, Adrian, Quinlan, Erin B, Rasser, Paul E, Ratnakar, Varun, Reppermund, Simone, Steen, Vidar M, Tooney, Paul A, Torres, Fábio R, Veltman, Dick J, Voyvodic, James T, Ashley-Koch, Allison, Whelan, Robert, White, Tonya, Yamamori, Hidenaga, Adams, Hieab H H, Bis, Joshua C, Debette, Stephanie, Decarli, Charles, Fornage, Myriam, Gudnason, Vilmundur, Hofer, Edith, Atkins, Joshua R, Ikram, M Arfan, Launer, Lenore, Longstreth, W. T., Lopez, Oscar L, Mazoyer, Bernard, Mosley, Thomas H, Roshchupkin, Gennady V, Satizabal, Claudia L, Schmidt, Reinhold, Seshadri, Sudha, Bernard, Manon, Yang, Qiong, Initiative, Alzheimer’s Disease Neuroimaging, Consortium, CHARGE, Consortium, EPIGEN, Consortium, IMAGEN, Consortium, SYS, Initiative, Parkinson’s Progression Markers, Alvim, Marina K M, Ames, David, Anderson, Tim J, Brouwer, Rachel M, Andreassen, Ole A, Arias-Vasquez, Alejandro, Bastin, Mark E, Baune, Bernhard T, Beckham, Jean C, Blangero, John, Boomsma, Dorret I, Brodaty, Henry, Brunner, Han G, Buckner, Randy L, Buimer, Elizabeth E L, Buitelaar, Jan K, Bustillo, Juan R, Cahn, Wiepke, Cairns, Murray J, Calhoun, Vince, Carr, Vaughan J, Caseras, Xavier, Caspers, Svenja, Cavalleri, Gianpiero L, Cendes, Fernando, Bülow, Robin, Corvin, Aiden, Crespo-Facorro, Benedicto, Dalrymple-Alford, John C, Dannlowski, Udo, de Geus, Eco J C, Deary, Ian J, Delanty, Norman, Depondt, Chantal, Desrivières, Sylvane, Donohoe, Gary, Bürger, Christian, Espeseth, Thomas, Fernández, Guillén, Fisher, Simon E, Flor, Herta, Forstner, Andreas J, Francks, Clyde, Franke, Barbara, Glahn, David C, Gollub, Randy L, Grabe, Hans J, Colodro-Conde, Lucía, Cannon, Dara M, Gruber, Oliver, Håberg, Asta K, Hariri, Ahmad R, Hartman, Catharina A, Hashimoto, Ryota, Heinz, Andreas, Henskens, Frans A, Hillegers, Manon H J, Hoekstra, Pieter J, Holmes, Avram J, Chakravarty, Mallar, Hong, L Elliot, Hopkins, William D, Hulshoff Pol, Hilleke E, Jernigan, Terry L, Jönsson, Erik G, Kahn, René S, Kennedy, Martin A, Kircher, Tilo T J, Kochunov, Peter, Kwok, John B J, Chen, Qiang, Le Hellard, Stephanie, Loughland, Carmel M, Martin, Nicholas G, Martinot, Jean-Luc, McDonald, Colm, McMahon, Katie L, Meyer-Lindenberg, Andreas, Michie, Patricia T, Morey, Rajendra A, Mowry, Bryan, Cheung, Joshua W, Nyberg, Lars, Oosterlaan, Jaap, Ophoff, Roel A, Pantelis, Christos, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W J H, Polderman, Tinca J C, Posthuma, Danielle, Rietschel, Marcella, Couvy-Duchesne, Baptiste, Roffman, Joshua L, Rowland, Laura M, Sachdev, Perminder S, Sämann, Philipp G, Schall, Ulrich, Schumann, Gunter, Scott, Rodney J, Sim, Kang, Sisodiya, Sanjay M, Smoller, Jordan W, Dale, Anders M, Sommer, Iris E, St Pourcain, Beate, Stein, Dan J, Toga, Arthur W, Trollor, Julian N, Van der Wee, Nic J A, van 't Ent, Dennis, Völzke, Henry, Walter, Henrik, Weber, Bernd, Dalvie, Shareefa, Weinberger, Daniel R, Wright, Margaret J, Zhou, Juan, Stein, Jason L, Thompson, Paul M, Medland, Sarah E, Consortium, Enhancing NeuroImaging Genetics through Meta-Analysis, Witte, A Veronica, Darin, Abigail, Fleisher, Adam, de Araujo, Tânia K, Pierce, Aimee, Mintz, Akiva, Lerner, Alan, Reith, Alastair D, Hofman, Albert, Espay, Alberto, Ihlenfeld, Albrecht, Ing, Alex, Iranzo, Alex, Beiser, Alexa S, de Zubicaray, Greig I, Norbash, Alexander, Barbot, Alexis, Rudolph, Alice, Portillo, Alicia, Chalker, Alison, Levey, Allan I, Rosen, Allyson, Smith, Amanda, Catafau, Ana, de Zwarte, Sonja M C, Ulysse, Anaztasia, Uitterlinden, André G, Becker, Andreas, Budson, Andrew E, Kertesz, Andrew, Siderowf, Andrew, Bralten, Janita, den Braber, Anouk, Singleton, Andrew, James, Angela, Oliver, Angela, Mishra, Aniket, Hake, Ann Marie, Burke, Anna, Sarrael, Antero, Porsteinsson, Anton P, Stringaris, Argyris, McCoy, Arita, Doan, Nhat Trung, Villringer, Arno, Lenahan, Art, Toga, Arthur, Bokde, Arun, Rawlins, Ashlee, Lamb, Ashley, Lee, Athena, Raj, Balebail Ashok, Tran, Baochan, Dohm, Katharina, Ruggeri, Barbara, Saba, Barbara, Lane, Barton, Yanez, Beatriz, Ances, Beau, Dunlop, Becky, Mudge, Benita, Ravina, Bernard, Ittermann, Bernd, Ehrlich, Stefan, van Noort, Betteke, Lind, Betty, Shah, Bina, Stefanovic, Bojana, Goldstein, Bonnie S, Bonakdarpour, Borna, Matthews, Brandy R, Borowski, Bret, Ott, Brian R, Reynolds, Brigid, Engelbrecht, Hannah-Ruth, Mollenhauer, Brit, Miller, Bruce L, Psaty, Bruce M, Spann, Bryan M, Sadowsky, Carl, Linder, Carly, Franz, Carol E, Tanner, Caroline, Kopil, Catherine, Thomas, Cathi-Ann, Erk, Susanne, Ward, Chad, Bernick, Charles, Smith, Charles D, DeCarli, Charles, Caspell, Chelsea, Deeley, Cheryl, Riordan, Cheryl, Mathis, Chet, Onyike, Chiadi, Heyn, Chris Chinthaka, Fan, Chun Chieh, Hosein, Chris, Leach, Christi, Bÿchel, Christian, Gigliotti, Christina, Hunter, Christine, Belden, Christine M, Tzourio, Christophe, Coffey, Christopher, van Dyck, Christopher H, Clark, Christopher M, Fedko, Iryna O, Wu, Chuang-Kuo, Albers, Colleen S, Chu, Congying, Brand, Connie, Isensee, Corinna, van Duijn, Cornelia M, Bishop, Courtney, Bodge, Courtney, Foley, Sonya F, Tatsuoka, Curtis, Casaceli, Cynthia, Carlsson, Cynthia M, Mathews, Dana, D'Agostino, Daniel, Silverman, Daniel H S, Marson, Daniel, Berg, Daniela, Harvey, Danielle, Jennings, Danna, Ford, Judith M, Wolk, David A, Goldstein, David B, Bachman, David, Brooks, David, Clark, David, Geldmacher, David, Hart, David, Holtzman, David, Jones, David, Hibar, Derrek P, Fukunaga, Masaki, Knopman, David, Hewitt, David L, Perry, David, Russell, David, Standaert, David, Winkfield, David, Green, Davis Robert C, Fontaine, Deborah, Miller, Delwyn D, Gessert, Devon, Garrett, Melanie E, Kerwin, Diana, Willeke, Diana, Drost, Dick, Papadopoulos, Dimitri, Rowe, Dominic, Simpson, Donna M, Muni, Donna, Galasko, Douglas, Scharre, Douglas W, Fillmer, Ariane, Ge, Tian, Bartha, Rob, Celmins, Dzintra, Zimmerman, Earl A, Teng, Edmond, Tolosa, Eduardo, Coleman, Edward, Zamrini, Edward, Mitsis, Effie, Finger, Elizabeth, Giddaluru, Sudheer, Oates, Elizabeth, Sosa, Elizabeth, Woo, Ellen, Rogalski, Emily, Lethbridge, Emma, Dooley, Eoin, Foster, Eric, Reiman, Eric M, Quinlan, Erin Burke, Goldman, Aaron L, Franklin, Erin, Heinzen, Erin L, Fletcher, Evan, Sprenger, Fabienne, Crivello, Fabrice, Biondo, Francesca, Parfitt, Francine, Hefti, Franz, Beyer, Frauke, Nees, Frauke, Green, Melissa J, Leonard, Gabriel, Robert, Gabriel, Thai, Gaby, Marshall, Gad A, Barker, Gareth, Conrad, Gary, Tremont, Geoffrey, Bartzokis, George, Groenewold, Nynke A, Hsiung, Ging-Yuek Robin, Malferrari, Giulia, Chiang, Gloria, Pearlson, Godfrey D, Liang, Grace, Jicha, Greg, Sorensen, Greg, Todd, Gretchen, Jimenez, Gustavo, Grotegerd, Dominik, Zare, Habil, Grabe, Hans Jörgen, Vanderswag, Helen, Schmidt, Helena, Venkov, Heli, Lemaitre, Hervé, Gurholt, Tiril P, Grossman, Hillel, Shill, Holly, Soares, Holly, Lin, Honghuang, Capote, Horacio, Bergman, Howard, Chertkow, Howard, Feldman, Howard, Fillit, Howard, Rosen, Howard J, Gutman, Boris A, Koleva, Hristina, Fernandez, Hubert, Garavan, Hugh, Shim, Hyungsub, Grachev, Igor D, Richard, Irene, Filippi, Irina, Rachinsky, Irina, Wurster, Isabel, Lind, Penelope A, Hansell, Narelle K, Mintzer, Jacobo, Ziolkowski, Jaimie, Brewer, James, Lah, James J, Leverenz, James, Becker, James T, Tetrud, James, Singleton-Garvin, Jamika, Egebjerg, Jan, Cellar, Janet S, Harris, Mathew A, Pentilla, Jani, Brosch, Jared R, Tinklenberg, Jared, Karlawish, Jason H, Meyer, Javier Villanueva, Himali, Jayandra J, Poline, Jean-Baptiste, Gunter, Jeff, Kaye, Jeffrey A, Harrison, Marc B, Dalley, Jeffrey, Burns, Jeffrey M, Petrella, Jeffrey R, Mule, Jennifer, Salazar, Jennifer, Rotter, Jerome I, Yesavage, Jerome, Cedarbaum, Jesse, Jiang, Jiyang, Haswell, Courtney C, Allard, Joanne, Lord, Joanne L, Hetelle, Joel, Kwok, John B, Brockington, John, Morris, John C, Hsiao, John, Morris, John, Olichney, John, Trojanowki, John Q, Hauser, Michael, Rogers, John, Seibyl, John, Yankey, Jon, Dubow, Jordan S, Jankovic, Joseph, Quinn, Joseph, Kass, Joseph S, Taylor, Joy L, Heidebrink, Judith L, Herms, Stefan, Trollor, Julian, Fröhner, Juliane, Anderson, Karen, Blank, Karen, Crawford, Karen, Smith, Karen Ekstam, Bell, Karen L, Williams, Karen, Kieburtz, Karl, Heslenfeld, Dirk J, Gauss, Katharina, Gloer, Katherine, Johnson, Kathleen, Tingus, Kathleen, DeMarco, Kathryn, Sink, Kaycee M, Hawkins, Keith A, Johnson, Keith A, Kantarci, Kejal, Ho, New Fei, Faber, Kelley, Harless, Kelly, Makino, Kelly M, Marek, Kenneth, Spicer, Kenneth, Shianna, Kevin, Chen, Kewei, Nam, Ki Won, Martin, Kim, Poki-Walker, Kim, Hoehn, David, Seppi, Klaus, Johnson, Kris, Fargher, Kristin, Lipowski, Kristine, Espay, Kristy, Womack, Kyle, Chahine, Lama, Flashman, Laura A, Daedelow, Laura, Hoffmann, Per, Leary, Laura, Beckett, Laurel, Honig, Lawrence S, Thal, Leon, Shaw, Leslie M, Kuller, Lew, Apostolova, Liana, Teodoro, Liberty, Rees, Linda, Pizzagalli, Fabrizio, Holleran, Laurena, Lewis, Lindsay, Hergesheimer, Lindsey, Silbert, Lisa C, Ravdin, Lisa, Taylor-Reinwald, Lisa, Uribe, Liz, Schneider, Lon S, Daiello, Lori A, Richer, Louis, Poustka, Luise, Hoogman, Martine, Pirpamer, Lukas, Mesulam, M Marcel, Ismail, M Saleem, Ranola, Madelaine, Korecka, Magdalena, Raichle, Marc, Seltzer, Marc, van der Brug, Marcel, Hottenga, Jouke-Jan, Mesulam, Marek-Marsel, Carrillo, Maria, Carroll, Maria, Knol, Maria J, Kataki, Maria, Greig-Custo, Maria T, Paillere, Marie-Laure, Albert, Marilyn, Love, Marissa Natelson, Ikeda, Masashi, Mintun, Mark A, Frasier, Mark, Logue, Mark, Minton, Mark, Loeffler, Markus, Scholz, Markus, Baca, Marne, Farlow, Martin R, Sadowski, Martin, Janowitz, Deborah, Creech, Mary L, Hynes, Mary L, Quiceno, Mary, Oakley, MaryAnn, Harris, Mat, Senjem, Matt, Bernstein, Matthew, Panizzon, Matthew S, Stern, Matthew, Becerra, Mauricio, Jansen, Iris E, Witbracht, Megan, Vernooij, Meike W, Brandabur, Melanie, Keltz, Melanie, Lamar, Melissa, Yang, Mia, Ahlijanian, Michael, Borrie, Michael, Neale, Michael C, Donohue, Michael, Jia, Tianye, Lyons, Michael J, Lin, Michael, Rapp, Michael, Smolka, Michael, Weiner, Michael W, Weiner, Michael, Figurski, Michal, Perron, Michel, Assaly, Michele, Luciano, Michelle, Jockwitz, Christiane, Rainka, Michelle, Dang, Mimi, Sheikh, Mohammed O, Ghanbari, Mohsen, Gaikwad, Mrunalini, Chowdhury, Munir, Trncic, Nadira, Amin, Najaf, Johnson, Nancy, Kanai, Ryota, Kowalksi, Nancy, Monahan, Nancy, Gillespie, Nathan A, Pacini, Nathaniel, Buckholtz, Neil, Kowall, Neil, Graff-Radford, Neill R, Fox, Nick, Pavese, Nicola, Karama, Sherif, Cairns, Nigel J, Schuff, Norbert, Foster, Norm, Relkin, Norman, Oyonumo, Ntekim E, Pomara, Nunzio, James, Olga, Ogunlana, Olu, Ching, Christopher R K, Kasperaviciute, Dalia, Carmichael, Owen, Doraiswamy, P Murali, Casalin, Paola, Barone, Paolo, Fatica, Parianne, Conrod, Patricia, Johnson, Patricia Lynn, Samuels, Patricia, Aisen, Paul, Malloy, Paul, Kaufmann, Tobias, Thompson, Paul, Ogrocki, Paula, Bezivin-Frere, Pauline, Maillard, Pauline, Fontoura, Paulo, Taylor, Peggy, Hogarth, Penelope, Gowland, Penny, Davies, Peter, Kelly, Sinead, Hardy, Peter, Snyder, Peter J, Snyder, Peter, Amouyel, Philippe, Muglia, Pierandrea, Tariot, Pierre, Lu, Po H, Varma, Pradeep, Vemuri, Prashanthi, Kikuchi, Masataka, Doody, Rachelle S, Carter, Raina, Shah, Raj C, Griffith, Randall, Yeh, Randy, Duara, Ranjan, Tarawneh, Rawan, James, Raymond, Turner, Raymond Scott, Klein, Marieke, Hernando, Raymundo, Silverstein, Rebecca, Sperling, Reisa A, Wilson, Renee, Carson, Richard E, Frank, Richard, El Khouli, Riham, Koeppe, Robert A, Santulli, Robert B, Knapp, Michael, Hauser, Robert, Umek, Robert, Radtke, Rodney, Killiany, Ronald, Petersen, Ronald, Rodriguez, Rosemarie, Miranda, Ruben, Knodt, Annchen R, Bruehl, Ruediger, Xia, Rui, Swerdlow, Russell H, Ottmann, Ruth, Millenet, Sabina, Borges-Neto, Salvador, Frank, Samuel, Black, Sandra, Weintraub, Sandra, Obradov, Sanja, Krämer, Bernd, Asthana, Sanjay, Vaishnavi, Sanjeev, Dolen, Sara, Mason, Sara S, Hohmann, Sarah, Kremen, Sarah, Miller, Sarah, Walter, Sarah, Herring, Scott, Neu, Scott, Lam, Max, Aydin, Semiha, Ahmad, Shahzad, Harlan, Sherry, Sirrel, Sherye A, Lasch, Shirley, Hu, Shu-Ching, Li, Shuo, Kittur, Smita, Chowdhury, Sohini, Lancaster, Thomas M, Pawluczyk, Sonia, Maingault, Sophie, Schneider, Stacy, Seiler, Stephan, Guthrie, Stephanie, Kielb, Stephanie, Reeder, Stephanie, Correia, Stephen, Pasternak, Stephen, McMahon, Mary Agnes B, Lee, Phil H, Salloway, Stephen, Johnson, Sterling, Williams, Steve, Chao, Steven, Arnold, Steven E, Paul, Steven, Potkin, Steven, Factor, Stewart, Isaacson, Stuart, Lett, Tristram A, Kim, Sungeun, Ainscough, Susan, Schultz, Susan K, Landau, Susan, Mendick, Susan, Rountree, Susan, Ostrowizki, Suzanne, Veillette, Suzanne, van der Lee, Sven J, Desrivieres, Sylvane, Lewis, Lindsay B, Lee, T-Y, Simuni, Tanya, Foroud, Tatiana, Foroud, Tatiana M, Wong, Terence Z, Villena, Teresa, Comery, Thomas, Obisesan, Thomas O, Lopes-Cendes, Iscia, Banaschewski, Tobias, Sherer, Todd, Montine, Tom, Paus, Tomáš, Robbins, Trevor, Bromberg, Uli, Völker, Uwe, Pavlik, Valory, Arnedo, Vanessa, Kiyasova, Vera, Bates, Vernice, Logovinsky, Veronika, Sossi, Vesna, Shibley, Victoria, Frouin, Vincent, Lee, Virginia, Poewe, Werner, Jagust, William, Brooks, William M, Macciardi, Fabio, Pavlosky, William, Potter, William, Kremen, William S, Longstreth, William T, Niessen, Wiro J, Jian, Xueqiu, Stern, Yaakov, Saba, Yasaman, Cabrera, Yuliana, Grimmer, Yvonne, Marquand, Andre F, Khachaturian, Zaven, Mari, Zoltan, Mathias, Samuel R, Melzer, Tracy R, Milaneschi, Yuri, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Movement Disorder (MD), Alzheimer’s Disease Neuroimaging Initiative, CHARGE Consortium, EPIGEN Consortium, IMAGEN Consortium, SYS Consortium, Parkinson’s Progression Markers Initiative, Stochastics, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, Science and Society, Cognitive Psychology, IBBA, APH - Personalized Medicine, Complex Trait Genetics, APH - Methodology, Clinical Neuropsychology, Sociology and Social Gerontology, Amsterdam Neuroscience - Complex Trait Genetics, RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, Klinische Genetica, RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA Klinische Genetica (5), Neurology, Psychiatry, Pediatric surgery, Amsterdam Reproduction & Development (AR&D), Human genetics, APH - Digital Health, Psychology, Precision Medicine Institute of Psychiatry, Child and Adolescent Psychiatry / Psychology, Radiology & Nuclear Medicine, Clinical Genetics, Epidemiology, Medical Informatics, Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Neurodegeneratives Diseases Institute (IMN-UMR CNRS 5293), Centre National de la Recherche Scientifique (CNRS), General Paediatrics, ARD - Amsterdam Reproduction and Development, Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay

Subjects
0301 basic medicine, Netherlands Twin Register (NTR), [SDV]Life Sciences [q-bio], LOCI, Genome-wide association study, Brain mapping, 0302 clinical medicine, Cognition, Cortex (anatomy), ComputingMilieux_MISCELLANEOUS, Cerebral Cortex, 0303 health sciences, Brain Mapping, Multidisciplinary, COMMON VARIANTS, Parkinson Disease, Organ Size, Central sulcus, Magnetic Resonance Imaging, medicine.anatomical_structure, Cerebral cortex, Neuroinformatics, EXPRESSION, endocrine system, central sulcus, SURFACE-AREA, Biology, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Genetic variation, medicine, Attention deficit hyperactivity disorder, Humans, General, Gene, METAANALYSIS, 030304 developmental biology, Progenitor, CORTICAL SULCI, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Genetic variants, Genetic Variation, Attention Deficit Disorder with Hyperactivity, Genetic Loci, Genome-Wide Association Study, functional annotation, medicine.disease, Genetic architecture, 030104 developmental biology, Evolutionary biology, OBSERVER-INDEPENDENT CHARACTERIZATION, Multiple comparisons problem, ddc:320, genome-wide association, Neuroscience, 030217 neurology & neurosurgery
Abstract

Enhancing NeuroImaging Genetics through Meta-Analysis Consortium (ENIGMA)—Genetics working group., The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.

Published
2020
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8. Associations of Pulse and Blood Pressure with Hippocampal Volume by APOE and Cognitive Phenotype: The Alzheimer’s Disease Neuroimaging Initiative (ADNI)

Author

Julius S. Ngwa, Thomas O. Obisesan, Alzheimer’s Disease Neuroimaging Initiative, Sheeba R. Nadarajah, Joanne S. Allard, Richard F. Gillum, Sheree M. Johnson, Lennox A. Graham, Thomas V. Fungwe, Oyonumo Ntekim, and Chimene Castor

Subjects
Male, Apolipoprotein E, medicine.medical_specialty, Genotype, Cognitive Neuroscience, Diastole, Prodromal Symptoms, Blood Pressure, Neuroimaging, Neuropsychological Tests, 030204 cardiovascular system & hematology, Hippocampal formation, Hippocampus, Article, 03 medical and health sciences, Apolipoproteins E, Cognition, 0302 clinical medicine, Alzheimer Disease, Heart Rate, Internal medicine, medicine, Humans, Hippocampus (mythology), Cognitive Dysfunction, Aged, Aged, 80 and over, business.industry, medicine.disease, Magnetic Resonance Imaging, Pulse pressure, Psychiatry and Mental health, Endocrinology, Blood pressure, Female, Geriatrics and Gerontology, Alzheimer's disease, business, 030217 neurology & neurosurgery, Alzheimer's Disease Neuroimaging Initiative
Abstract

Background: It is increasingly evident that high blood pressure can promote reduction in global and regional brain volumes. While these effects may preferentially affect the hippocampus, reports are inconsistent. Methods: Using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), we examined the relationships of hippocampal volume to pulse pressure (PPR) and systolic (SBP) and diastolic (DBP) blood pressure according to apolipoprotein (APOE) ɛ4 positivity and cognitive status. The ADNI data included 1,308 participants: Alzheimer disease (AD = 237), late mild cognitive impairment (LMCI = 454), early mild cognitive impairment (EMCI = 254), and cognitively normal (CN = 365), with up to 24 months of follow-up. Results: Higher quartiles of PPR were significantly associated with lower hippocampal volumes (Q1 vs. Q4, p = 0.034) in the CN and AD groups, but with increasing hippocampal volume (Q1, p = 0.008; Q2, p = 0.020; Q3, p = 0.017; Q4 = reference) in the MCI groups. In adjusted stratified analyses among non-APOE ɛ4 carriers, the effects in the CN (Q1 vs. Q4, p = 0.006) and EMCI groups (Q1, p = 0.002; Q2, p = 0.013; Q3, p = 0.002; Q4 = reference) remained statistically significant. Also, higher DBP was significantly associated with higher hippocampal volume (p = 0.002) while higher SBP was significantly associated with decreasing hippocampal volume in the EMCI group (p = 0.015). Conclusion: Changes in PPR, SBP, and DBP differentially influenced hippocampal volumes depending on the cognitive and APOE genotypic categories.

Published
2018
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9. Dual-Model Radiomic Biomarkers Predict Development of Mild Cognitive Impairment Progression to Alzheimer's Disease

Author

Zhou, Hucheng, Jiang, Jiehui, Lu, Jiaying, Wang, Min, Zhang, Huiwei, Zuo, Chuantao, Weiner, Michael W, Aisen, Paul, Petersen, Ronald, Jr, Jack Clifford R, Jagust, William, Trojanowki, John Q, Toga, Arthur W, Beckett, Laurel, Green, Robert C, Saykin, Andrew J, Morris, John, Shaw, Leslie M, Khachaturian, Zaven, Sorensen, Greg, Carrillo, Maria, Kuller, Lew, Raichle, Marc, Paul, Steven, Davies, Peter, Fillit, Howard, Hefti, Franz, Holtzman, David, Mesulam, M Marcel, Potter, William, Snyder, Peter, Lilly, Eli, Montine, Tom, Jimenez, Gustavo, Donohue, Michael, Gessert, Devon, Harless, Kelly, Salazar, Jennifer, Cabrera, Yuliana, Walter, Sarah, Hergesheimer, Lindsey, Harvey, Danielle, Bernstein, Matthew, Fox, Nick, Thompson, Paul, Schuff, Norbert, DeCArli, Charles, Borowski, Bret, Gunter, Jeff, Senjem, Matt, Vemuri, Prashanthi, Jones, David, Kantarci, Kejal, Ward, Chad, Koeppe, Robert A, Foster, Norm, Reiman, Eric M, Chen, Kewei, Mathis, Chet, Logovinsky, Veronika, Morris, John C, Cairns, Nigel J, Franklin, Erin, Taylor-Reinwald, Lisa, Lee, Virginia, Korecka, Magdalena, Figurski, Michal, Crawford, Karen, Neu, Scott, Foroud, Tatiana M, Potkin, Steven, Shen, Li, Faber, Kelley, Kim, Sungeun, Nho, Kwangsik, Thal, Lean, Thal, Leon, Buckholtz, Neil, Snyder, Peter J, Albert, Marilyn, Frank, Richard, Hsiao, John, Landau, Susan, Quinn, Joseph, Silbert, Lisa C, Lind, Betty, Kaye, Jeffrey A, Carter, Raina, Dolen, Sara, Schneider, Lon S, Pawluczyk, Sonia, Becerra, Mauricio, Teodoro, Liberty, Spann, Bryan M, Brewer, James, Vanderswag, Helen, Fleisher, Adam, Ziolkowski, Jaimie, Heidebrink, Judith L, Lord, Joanne L, Mason, Sara S, Albers, Colleen S, Knopman, David, Johnson, Kris, Villanueva-Meyer, Javier, Pavlik, Valory, Pacini, Nathaniel, Lamb, Ashley, Kass, Joseph S, Doody, Rachelle S, Shibley, Victoria, Chowdhury, Munir, Rountree, Susan, Dang, Mimi, Stem, Yaakov, Honig, Lawrence S, Bell, Karen L, Yeh, Randy, Ances, Beau, Winkfield, David, Carroll, Maria, Oliver, Angela, Creech, Mary L, Mintun, Mark A, Schneider, Stacy, Marson, Daniel, Geldmacher, David, Love, Marissa Natelson, Griffith, Randall, Clark, David, Brockington, John, Grossman, Hillel, Mitsis, Effie, Shah, Raj C, Lamar, Melissa, Samuels, Patricia, Duara, Ranjan, Greig-Custo, Maria T, Rodriguez, Rosemarie, Onyike, Chiadi, II, D'Agostino Daniel, Kielb, Stephanie, Sadowski, Martin, Sheikh, Mohammed O, Singleton-Garvin, Jamika, Ulysse, Anaztasia, Gaikwad, Mrunalini, Doraiswamy, P Murali, Petrella, Jeffrey R, James, Olga, Borges-Neto, Salvador, Wong, Terence Z, Coleman, Edward, Karlawish, Jason H, Wolk, David A, Vaishnavi, Sanjeev, Clark, Christopher M, Arnold, Steven E, Smith, Charles D, Jicha, Greg, Hardy, Peter, El Khouli, Riham, Oates, Elizabeth, Conrad, Gary, Lopez, Oscar L, Oakley, MaryAnn, Simpson, Donna M, Porsteinsson, Anton P, Martin, Kim, Kowalksi, Nancy, Keltz, Melanie, Goldstein, Bonnie S, Makino, Kelly M, Ismail, M Saleem, Brand, Connie, Thai, Gaby, Pierce, Aimee, Yanez, Beatriz, Sosa, Elizabeth, Witbracht, Megan, Womack, Kyle, Mathews, Dana, Quiceno, Mary, Levey, Allan I, Lah, James J, Cellar, Janet S, Burns, Jeffrey M, Swerdlow, Russell H, Brooks, William M, Woo, Ellen, Silverman, Daniel HS, Teng, Edmond, Kremen, Sarah, Apostolova, Liana, Tingus, Kathleen, Lu, Po H, Bartzokis, George, Graff-Radford, Neill R, Parfitt, Francine, Poki-Walker, Kim, Farlow, Martin R, Hake, Ann Marie, Matthews, Brandy R, Brosch, Jared R, Herring, Scott, van Dyck, Christopher H, Carson, Richard E, Varma, Pradeep, Chertkow, Howard, Bergman, Howard, Hosein, Chris, Black, Sandra, Stefanovic, Bojana, Heyn, Chris Chinthaka, Hsiung, Ging-Yuek Robin, Mudge, Benita, Sossi, Vesna, Feldman, Howard, Assaly, Michele, Finger, Elizabeth, Pasternack, Stephen, Pavlosky, William, Rachinsky, Irina, Drost, Dick, Kertesz, Andrew, Bernick, Charles, Munic, Donna, Mesulam, Marek-Marsel, Rogalski, Emily, Lipowski, Kristine, Weintraub, Sandra, Bonakdarpour, Borna, Kerwin, Diana, Wu, Chuang-Kuo, Johnson, Nancy, Sadowsky, Carl, Villena, Teresa, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, Sperling, Reisa A, Johnson, Keith A, Marshall, Gad A, Yesavage, Jerome, Taylor, Joy L, Chao, Steven, Lane, Barton, Rosen, Allyson, Tinklenberg, Jared, Zamrini, Edward, Belden, Christine M, Sirrel, Sherye A, Kowall, Neil, Killiany, Ronald, Budson, Andrew E, Norbash, Alexander, Johnson, Patricia Lynn, Obisesan, Thomas O, Oyonumo, Ntekim E, Allard, Joanne, Nlana, Olu Ogu, Lerner, Alan, Ogrocki, Paula, Tatsuoka, Curtis, Fatica, Parianne, Fletcher, Evan, Maillard, Pauline, Olichney, John, Carmichael, Owen, Kittur, Smita, Borrie, Michael, Lee, T-Y, Bartha, Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M, Tariot, Pierre, Burke, Anna, Hetelle, Joel, DeMarco, Kathryn, Trncic, Nadira, Reeder, Stephanie, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Scharre, Douglas W, Kataki, Maria, Tarawneh, Rawan, Zimmerman, Earl A, Celmins, Dzintra, Hart, David, Pearlson, Godfrey D, Blank, Karen, Anderson, Karen, Flashman, Laura A, Seltzer, Marc, Hynes, Mary L, Santulli, Robert B, Sink, Kaycee M, Yang, Mia, Mintz, Akiva, Ott, Brian R, Tremont, Geoffrey, Daiello, Lori A, Bodge, Courtney, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Lee, Athena, Rosen, Howard J, Miller, Bruce L, Perry, David, Mintzer, Jacobo, Spicer, Kenneth, Bachman, David, Pasternak, Stephen, Rogers, John, Pomara, Nunzio, Hernando, Raymundo, Sarrael, Antero, Miller, Delwyn D, Smith, Karen Ekstam, Koleva, Hristina, Nam, Ki Won, Shim, Hyungsub, Schultz, Susan K, Relkin, Norman, Chiang, Gloria, Lin, Michael, Ravdin, Lisa, Smith, Amanda, Leach, Christi, Raj, Balebail Ashok, Fargher, Kristin, Neylan, Thomas, Grafman, Jordan, Hergesheimen, Lindsey, Hayes, Jacqueline, Finley, Shannon, Householder, Erin, Fleischman, Debra, Arfanakis, Konstantinos, Varon, Daniel, Greig, Maria T, Goldstein, Bonnie, Martin, Kimberly S, Potkin, Steven G, Preda, Adrian, Nguyen, Dana, Massoglia, Dino, Brawman-Mintzer, Olga, Martinez, Walte R, Rosen, Howard, Behan, Kelly, Marshall, Gad, Sabbagh, Marwan N, Jacobson, Sandra A, Wolday, Saba, Johnson, Sterling C, Fruehling, J Jay, Harding, Sandra, Peskind, Elaine R, Petrie, Eric C, Li, Gail, Yesavage, Jerome A, Furst, Ansgar J, Mackin, Scott, Raman, Rema, Drake, Erin, Donohue, Mike, Shaffe, Elizabeth, Nelson, Craig, Bickford, David, Butters, Meryl, Zmuda, Michelle, Reyes, Denise, Nudelman, Kelly N, Au, Yiu Ho, Scherer, Kelly, Catalinotto, Daniel, Stark, Samuel, Ong, Elise, Fernandez, Dariella, and Initia, Alzheimers Dis Neuroimaging

Subjects
mild cognitive impairment, radiomics, Cox model, Neurosciences, Cognitive Science, Alzheimer’s Disease Neuroimaging Initiative, Alzheimer's disease, image fusion, Alzheimer’s disease
Abstract

Predicting progression of mild cognitive impairment (MCI) to Alzheimer's disease (AD) is clinically important. In this study, we propose a dual-model radiomic analysis with multivariate Cox proportional hazards regression models to investigate promising risk factors associated with MCI conversion to AD. T1 structural magnetic resonance imaging (MRI) and 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) data, from the AD Neuroimaging Initiative database, were collected from 131 patients with MCI who converted to AD within 3 years and 132 patients with MCI without conversion within 3 years. These subjects were randomly partition into 70% training dataset and 30% test dataset with multiple times. We fused MRI and PET images by wavelet method. In a subset of subjects, a group comparison was performed using a two-sample t-test to determine regions of interest (ROIs) associated with MCI conversion. 172 radiomic features from ROIs for each individual were established using a published radiomics tool. Finally, L1-penalized Cox model was constructed and Harrell's C index (C-index) was used to evaluate prediction accuracy of the model. To evaluate the efficacy of our proposed method, we used a same analysis framework to evaluate MRI and PET data separately. We constructed prognostic Cox models with: clinical data, MRI images, PET images, fused MRI/PET images, and clinical variables and fused MRI/PET images in combination. The experimental results showed that captured ROIs significantly associated with conversion to AD, such as gray matter atrophy in the bilateral hippocampus and hypometabolism in the temporoparietal cortex. Imaging model (MRI/PET/fused) provided significant enhancement in prediction of conversion compared to clinical models, especially the fused-modality Cox model. Moreover, the combination of fused-modality imaging and clinical variables resulted in the greatest accuracy of prediction. The average C-index for the clinical/MRI/PET/fused/combined model in the test dataset was 0.69, 0.73, 0.73 and 0.75, and 0.78, respectively. These results suggested that a combination of radiomic analysis and Cox model analyses could be used successfully in survival analysis and may be powerful tools for personalized precision medicine patients with potential to undergo conversion from MCI to AD.

Published
2019
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10. Additive effects of Capsaicin Oleoresin, Irbesartan and Amlodipine Besylate on the blood pressure of spontaneously hypertensive rats

Author

Thomas O. Obisesan, Allan A. Johnson, Thomas V. Fungwe, Julius S. Ngwa, Chimene Castor, Oyonumo Ntekim, Osi Iyalomhe, Joanne S. Allard, and Chinwe C. Ntekim

Subjects
medicine.medical_specialty, Vasopressin, Arginine, Pharmaceutical Science, Plant Science, 030204 cardiovascular system & hematology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Irbesartan, Internal medicine, Drug Discovery, Renin–angiotensin system, Medicine, 030212 general & internal medicine, Amlodipine, Pharmacology, Aldosterone, business.industry, Endocrinology, Blood pressure, Complementary and alternative medicine, chemistry, Capsaicin, lipids (amino acids, peptides, and proteins), business, medicine.drug
Abstract

The effects of oral intake of capsaicin oleoresin (CO) on arterial blood pressure was examined in male spontaneously hypertensive (SHR) rats. Animals were randomized into control (C), capsaicin oleoresin (CO), capsaicin oleoresin-irbesartan (COI) and capsaicin oleoresin-amlodipine besylate (COAB) fed groups. The experimental groups received 50 mg of Capsaicin Oleoresin only, CO with 25 mg of Irbesartan, and CO with 2.5 mg of Amlodipine per kilogram of body weight every other day for 4 weeks. Blood pressure was measured weekly by tail-cuff for 4 weeks. Biological samples were obtained at baseline, day 18, and day 34 (terminal) for aldosterone, arginine vasopressin (AVP), renin, 6-Keto-PGF-1α, Prostaglandin E2, catecholamines, adrenocorticotropic hormone (ACTH) levels, and serum minerals. Statistical significance was set at p≤0.05. The results trended towards decreasing (p=0.190) systolic blood pressure (SBP) in the COAB and CO compared to the COI and control groups. However, significance among group differences were observed for urine aldosterone and AVP, and serum sodium, calcium, magnesium, potassium, and catecholamine (p≤0.05), but not for ACTH, renin, and 6-Keto-PGF-1α levels. Capsaicin treatment was non-significantly associated with decreased SBP in SHR. These findings suggested that the effects of Capsaicin on SPB may involve aldosterone and arteriolar vascular tone. Key words: Capsaicin oleoresin, amlodipine besylate, irbesartan, arginine vasopressin, spontaneously hypertensive rats.

Published
2016
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11. Plasma Lipid Profiles of Transgenic mice expressing the Human ApoB100XCETP are altered differentially by Diets enriched with defined Fatty Acids

Author

Oyonumo Ntekim, Wael Hatahet, Abdul Soofi, and Thomas V. Fungwe

Subjects
Apolipoprotein B, biology, Cholesterol, Medicine (miscellaneous), Metabolism, Carbohydrate, chemistry.chemical_compound, chemistry, Biochemistry, Acyltransferase, biology.protein, Cholesteryl ester, lipids (amino acids, peptides, and proteins), Triolein, Scavenger receptor, Food Science
Abstract

Dietary fat is known to modulate plasma lipid profiles. Synthesis of high density lipoproteins (HDL), which has protective effects on vascular disease is also influenced by dietary fats, but the mechanisms are unclear. The hapoB100XCETP transgenic mouse was used to investigate the effects of fatty acids on the metabolism of plasma lipoproteins, including the pathway leading to synthesis HDL. Male transgenic mice were fed with diets formulated to provide TG (33% energy) as tripalmitin (TP), triolein (TO), tristearin (TS) or equicaloric substitution of fat with carbohydrate (sucrose) for 4 weeks. Analysis of plasma profile showed that HDL-cholesterol were 53.7+14; 64.6+8.6; 50.2+3.3; 47.0+9.2 and 45.2+4.9 mg/dL for control, oleate, palmitate, stearate and sucrose based diets, respectively. LDL-cholesterol levels were 51.7+7.0; 23.1+7.0; 38.9+2.2; 75.1+1.8 and 46.8.1.0 mg/dl, for control, TO, TP, TS and sucrose, respectively. Hepatic Lecithin-cholesterol acyltransferase (LCAT) protein levels increased by 2-fold in mice fed TS or TO diets, compared to TP, while sucrose had no effect. The scavenger receptor class B type I (SR-B1) which plays an important role in meditating the uptake of HDL-derived cholesterol and cholesteryl ester in the liver and steroidogenic tissues increased in livers of animals fed TP and TO, while TS and sucrose did not have a similar effects. These results suggests that fatty acids can uniquely impact HDL, in addition, the ApoB100XCETP mouse is a useful model for the evaluation of how dietary components affect the risk of developing atherosclerosis and heart disease. key words: ApoB100, CETP, TC, HDL-C, LDL-C & TG, Transgenic.

Published
2015
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12. P2-589: ASSOCIATION OF DIFFERENT TYPES OF PHYSICAL ACTIVITY WITH PERFORMANCE ON COGNITIVE TASKS IN A PREDOMINANTLY AFRICAN AMERICAN SAMPLE

Author

Oyonumo Ntekim, Oludolapo Ogunlana, Thomas O. Obisesan, Thomas V. Fungwe, Javed Khan, Julius S. Ngwa, Saba Wolday, Lennox A. Graham, Steven Johnson, Richard F. Gillum, Chimene Castor, Sheeba R. Nadarajah, Mara Ramirezruiz, and Jillian Turner

Subjects
African american, Elementary cognitive task, Epidemiology, Health Policy, Physical activity, Sample (statistics), Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Neurology (clinical), Geriatrics and Gerontology, Psychology, Association (psychology), Clinical psychology
Published
2019
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13. P3-453: NORMATIVE DATA ON THE MONTREAL COGNITIVE ASSESSMENT FOR AN OLDER AMERICAN POPULATION

Author

Mara Ramirez, Steven Johnson, Oyonumo Ntekim, Saba Wolday, Sharlene L. Jeffers, Oludolapo Ogunlana, Chimene Castor, Jillian Turner, Richard F. Gillum, Joanne S. Allard, Thomas V. Fungwe, and Thomas O. Obisesan

Subjects
Gerontology, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, American population, Montreal Cognitive Assessment, Normative, Neurology (clinical), Geriatrics and Gerontology, Psychology
Published
2019
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14. A standardized randomized 6-month aerobic exercise-training down-regulated pro-inflammatory genes, but up-regulated anti-inflammatory, neuron survival and axon growth-related genes

Author

Osigbemhe Iyalomhe, Thomas O. Obisesan, Sheree M. Johnson, Oyonumo Ntekim, Yuanxiu Chen, Vernon Bond, Joanne S. Allard, James Li, and David Goerlitz

Subjects
Male, Aging, Pathology, medicine.medical_specialty, Microarray, Statistics as Topic, Down-Regulation, Inflammation, Biology, Biochemistry, Article, Oxygen Consumption, Endocrinology, Downregulation and upregulation, Internal medicine, Muscle Stretching Exercises, Gene expression, medicine, Genetics, Aerobic exercise, Humans, Cognitive Dysfunction, Nervous System Physiological Phenomena, Exercise, Molecular Biology, Aged, Gene Expression Profiling, VO2 max, Mild cognitive impairment, Cell Biology, Phenotype, Up-Regulation, Gene expression profiling, Ageing, Treatment Outcome, Female, medicine.symptom, Genome-Wide Association Study
Abstract

There is considerable support for the view that aerobic exercise may confer cognitive benefits to mild cognitively impaired elderly persons. However, the biological mechanisms mediating these effects are not entirely clear. As a preliminary step towards informing this gap in knowledge, we enrolled older adults confirmed to have mild cognitive impairment (MCI) in a 6-month exercise program. Male and female subjects were randomized into a 6-month program of either aerobic or stretch (control) exercise. Data collected from the first 10 completers, aerobic exercise (n=5) or stretch (control) exercise (n=5), were used to determine intervention-induced changes in the global gene expression profiles of the aerobic and stretch groups. Using microarray, we identified genes with altered expression (relative to baseline values) in response to the 6-month exercise intervention. Genes whose expression were altered by at least two-fold, and met the p-value cutoff of 0.01 were inputted into the Ingenuity Pathway Knowledge Base Library to generate gene-interaction networks. After a 6-month aerobic exercise-training, genes promoting inflammation became down-regulated, whereas genes having anti-inflammatory properties and those modulating immune function or promoting neuron survival and axon growth, became up-regulated (all fold change≥±2.0, p

Published
2015
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15. [P4–422]: EXERCISE TRAINING‐INDUCED CHANGES ON DNA METHYLATION IN MILD COGNITIVELY IMPAIRED OLDER AFRICAN AMERICANS: GEMS STUDY

Author

Steven Johnson, Chimene Castor, Oyonumo Ntekim, Oludolapo Ogunlana, Joanne S. Allard, Thomas V. Fungwe, Julius S. Ngwa, Thomas O. Obisesan, Lennox A. Graham, and Saba Wolday

Subjects
Gerontology, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, business.industry, Health Policy, DNA methylation, Medicine, Neurology (clinical), Cognitively impaired, Geriatrics and Gerontology, business
Published
2017
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16. [P4–559]: EXERCISE TRAINING‐INDUCED CHANGES ON POSITRON EMISSION TOMOGRAPHY (PET) WITH 2‐DEOXY‐2‐[ 18 F]FLUORO‐D‐GLUCOSE ([ 18 F]FDG) IN MILD COGNITIVELY IMPAIRED OLDER AFRICAN AMERICANS: GEMS STUDY

Author

Thomas V. Fungwe, Julius S. Ngwa, James B. Brewer, Oyonumo Ntekim, Joanne S. Allard, and Thomas O. Obisesan

Subjects
medicine.diagnostic_test, Epidemiology, business.industry, Health Policy, 03 medical and health sciences, Psychiatry and Mental health, Cellular and Molecular Neuroscience, 0302 clinical medicine, Developmental Neuroscience, Positron emission tomography, medicine, 030212 general & internal medicine, Neurology (clinical), Cognitively impaired, Geriatrics and Gerontology, Nuclear medicine, business
Published
2017
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17. [P3–187]: EFFECTS OF EXERCISE ON PLASMA NITRITE/NITRATE LEVELS, AND NITRIC OXIDE SYNTHASE ACTIVITY IN ELDERLY AFRICAN AMERICANS WITH MILD COGNITIVE IMPAIRMENT

Author

Thomas V. Fungwe, Richard F. Gillum, Graham A. Lennox, Joanne S. Allard, Thomas O. Obisesan, Oyonumo Ntekim, Chimene Castor, and Julius S. Ngwa

Subjects
medicine.medical_specialty, biology, Epidemiology, Health Policy, Nitric oxide synthase, Psychiatry and Mental health, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Endocrinology, Developmental Neuroscience, Nitrate, chemistry, Internal medicine, biology.protein, medicine, Neurology (clinical), Geriatrics and Gerontology, Nitrite, Cognitive impairment
Published
2017
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18. [P2–527]: NORMATIVE ANALYSIS OF MINI MENTAL STATE EXAMINATION: A CROSS SECTIONAL STUDY IN A PREDOMINANTLY AFRICAN AMERICAN SAMPLE

Author

Chimene Castor, Saba Wolday, Thomas O. Obisesan, Lennox A. Graham, Julius S. Ngwa, Oludolapo Ogunlana, Joanne S. Allard, Steven Johnson, Thomas V. Fungwe, Sharlene Leong, and Oyonumo Ntekim

Subjects
African american, Gerontology, Mini–Mental State Examination, medicine.diagnostic_test, Epidemiology, Cross-sectional study, Health Policy, Sample (statistics), Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, medicine, Neurology (clinical), Normative analysis, Geriatrics and Gerontology, Psychology
Published
2017
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19. P3-190: FBXO32 AND FOXO1 ARE COORDINATELY EXPRESSED IN A ONE-TO-ONE STOICHIOMETRIC PATTERN AT BASELINE, DURING EXERCISE AND IN BOTH GENDERS IN ELDERLY AFRICAN AMERICANS WITH MCI

Author

Thomas V. Fungwe, Fikru B. Bedada, Julius S. Ngwa, Oyonumo Ntekim, and Thomas O. Obisesan

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, medicine.medical_specialty, Developmental Neuroscience, Epidemiology, business.industry, Health Policy, Internal medicine, medicine, Neurology (clinical), Geriatrics and Gerontology, Baseline (configuration management), business
Published
2019
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20. A 'Food as Medicine' Program and It’s Effects on Healthy Eating and Cooking Confidence (P04-021-19)

Author

Julius S. Ngwa, DeAnna Nara, Linda Thompson, Chimene Castor, Allan A. Johnson, and Oyonumo Ntekim

Subjects
Gerontology, Nutrition and Dietetics, Mindfulness, business.industry, Nutrition Education, Medicine (miscellaneous), Type 2 Diabetes Mellitus, Health literacy, medicine.disease, Obesity, Community and Public Health Nutrition, Intervention (counseling), Food choice, Medicine, Prediabetes, business, Food Science
Abstract

OBJECTIVES: The aims of this study were to develop and implement a “Food as Medicine” intervention using quantitative methods supported by health literacy and food choice and behavioral models to target chronic diseases under free-living conditions in adults diagnosed with chronic diseases. The hypothesis of this study is that “Food as Medicine” nutrition and lifestyle intervention sessions will result in significant improvements in food choices, as well as shopping and cooking behaviors. METHODS: The Food as Medicine (FAM) study is a community-based pilot study that measured the effectiveness of a nutrition intervention to improve chronic disease risk factors and outcomes among African Americans with either pre-diabetes, type 2 diabetes mellitus, hypertension, elevated total blood cholesterol levels, obesity or a combination of these disorders. The study enrolled patients who were attending both Howard University Family Medicine and Internal Medicine Practices, and were residents of wards seven or eight in the District of Columbia. Fifty-four participants were enrolled and assigned to five cohorts, which consisted of five group sessions over three months, and focused on improving diet and health literacy through nutritionist-led, culturally-tailored, nutrition education classes that included health literacy, mindfulness exercises, and cooking demonstrations. RESULTS: After program completion, FAM participants demonstrated significant improvements in all outcome measures of interest: healthy dietary patterns (P

Published
2019
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22. The Role of Hypoxia-Inducible Factor 1 in Mild Cognitive Impairment

Author

Oyonumo Ntekim, Osigbemhe Iyalomhe, Sabina Swierczek, Yuanxiu Chen, Philip Kurian, Kakra Hughes, Monica O. Adedeji, Ngozi Enwerem, Joanne S. Allard, Sheree M. Johnson, and Thomas O. Obisesan

Subjects
0301 basic medicine, Apoptosis, Oxidative phosphorylation, medicine.disease_cause, Neuroprotection, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Alzheimer Disease, Memory, medicine, Dementia, Animals, Humans, Cognitive Dysfunction, Cognitive decline, Transcription factor, Neuroinflammation, Cell Biology, General Medicine, Hypoxia (medical), medicine.disease, Hypoxia-Inducible Factor 1, alpha Subunit, 030104 developmental biology, Cerebrovascular Circulation, medicine.symptom, Psychology, Neuroscience, 030217 neurology & neurosurgery, Oxidative stress
Abstract

Neuroinflammation and reactive oxygen species are thought to mediate the pathogenesis of Alzheimer’s disease (AD), suggesting that mild cognitive impairment (MCI), a prodromal stage of AD, may be driven by similar insults. Several studies document that hypoxia-inducible factor 1 (HIF-1) is neuroprotective in the setting of neuronal insults, since this transcription factor drives the expression of critical genes that diminish neuronal cell death. HIF-1 facilitates glycolysis and glucose metabolism, thus helping to generate reductive equivalents of NADH/NADPH that counter oxidative stress. HIF-1 also improves cerebral blood flow which opposes the toxicity of hypoxia. Increased HIF-1 activity and/or expression of HIF-1 target genes, such as those involved in glycolysis or vascular flow, may be an early adaptation to the oxidative stressors that characterize MCI pathology. The molecular events that constitute this early adaptation are likely neuroprotective, and might mitigate cognitive decline or the onset of full-blown AD. On the other hand, prolonged or overwhelming stressors can convert HIF-1 into an activator of cell death through agents such as Bnip3, an event that is more likely to occur in late MCI or advanced Alzheimer’s dementia.

Published
2016

23. APOEε4 Impacts Up-Regulation of Brain-Derived Neurotrophic Factor After a Six-Month Stretch and Aerobic Exercise Intervention in Mild Cognitively Impaired Elderly African Americans: A Pilot Study

Author

Thomas V. Fungwe, Richard F. Gillum, Dynell Pinder, Oyonumo Ntekim, Vernon Bond, John Kwagyan, Joanne S. Allard, Steven Johnson, Julius S. Ngwa, and Thomas O. Obisesan

Subjects
0301 basic medicine, Gerontology, Oncology, Apolipoprotein E, Male, Aging, medicine.medical_specialty, Heterozygote, Population, Apolipoprotein E4, Physical exercise, Pilot Projects, Disease, Biochemistry, Article, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Cognition, Neurotrophic factors, Internal medicine, Neuroplasticity, medicine, Genetics, Aerobic exercise, Humans, Cognitive Dysfunction, Genetic Predisposition to Disease, 10. No inequality, education, Molecular Biology, Exercise, Alleles, Aged, Brain-derived neurotrophic factor, Aged, 80 and over, education.field_of_study, business.industry, Brain-Derived Neurotrophic Factor, Cell Biology, 3. Good health, Exercise Therapy, Black or African American, Ageing, 030104 developmental biology, Female, business, 030217 neurology & neurosurgery
Abstract

Possession of the Apolipoprotein E (APOE) gene ε4 allele is the most prevalent genetic risk factor for late onset Alzheimer’s disease (AD). Recent evidence suggests that APOE genotype differentially affects the expression of brain-derived neurotrophic factor (BDNF). Notably, aerobic exercise-induced upregulation of BDNF is well documented; and exercise has been shown to improve cognitive function. As BDNF is known for its role in neuroplasticity and survival, its upregulation is a proposed mechanism for the neuroprotective effects of physical exercise. In this pilot study designed to analyze exercise-induced BDNF upregulation in an understudied population, we examined the effects of ApoEε4 (ε4) carrier status on changes in BDNF expression after a standardized exercise program. African Americans, age 55 years and older, diagnosed with mild cognitive impairment participated in a six-month, supervised program of either stretch (control treatment) or aerobic (experimental treatment) exercise. An exercise-induced increase in VO2Max was detected only in male participants. BDNF levels in serum were measured using ELISA. Age, screening MMSE scores and baseline measures of BMI, VO2Max, and BDNF did not differ between ε4 carriers and non-ε4 carriers. A significant association between ε4 status and serum BDNF levels was detected. Non-ε4 carriers showed a significant increase in BDNF levels at the 6 month time point while ε4 carriers did not. We believe we have identified a relationship between the ε4 allele and BDNF response to physiologic adaptation which likely impacts the extent of neuroprotective benefit gained from engagement in physical exercise. Replication of our results with inclusion of diverse racial cohorts, and a no-exercise control group will be necessary to determine the scope of this association in the general population.

Published
2016

24. P3‐258: Pulse pressure and systolic blood pressure associated with hippocampal volume by apolipoprotein (APO) carriers and Alzheimer disease status: Alzheimer's disease neuroimaging initiative (ADNI) study

Author

Julius S. Ngwa, Oyonumo Ntekim, Sheree M. Johnson, Thomas V. Fungwe, Chimene Castor, Thomas O. Obisesan, Joanne S. Allard, and Richard F. Gillum

Subjects
medicine.medical_specialty, Pathology, Apolipoprotein B, biology, Epidemiology, business.industry, Health Policy, medicine.disease, Pulse pressure, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Blood pressure, Developmental Neuroscience, Internal medicine, biology.protein, Hippocampal volume, Cardiology, Medicine, Neurology (clinical), Geriatrics and Gerontology, Alzheimer's disease, business, Alzheimer's Disease Neuroimaging Initiative
Published
2015
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25. P2‐216: Best strategies to recruit and enroll african americans into clinical and biomedical research

Author

Oyonumo Ntekim, Julius S. Ngwa, Steven Johnson, Thomas O. Obisesan, Saba Wolday, Megan Johson, Oludolapo Ogunlana, and Lennox A. Graham

Subjects
Gerontology, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, business.industry, Health Policy, Medicine, Neurology (clinical), Geriatrics and Gerontology, business
Published
2015
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26. P3‐234: Exercise‐induced effects on serum and CSF BDNF levels in elderly african americans with mild cognitive impairment: Gene, exercise, and memory study (GEMS)

Author

Sheree M. Johnson, Joanne S. Allard, Julius S. Ngwa, Oyonumo Ntekim, Thomas V. Fungwe, Richard F. Gillum, and Thomas O. Obisesan

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, medicine.medical_specialty, Developmental Neuroscience, Epidemiology, Health Policy, medicine, Neurology (clinical), Geriatrics and Gerontology, Cognitive impairment, Psychiatry, Psychology
Published
2015
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