418 results on '"Kandimalla, Ramesh"'
Search Results
102. Corrigendum: Mitochondrial division inhibitor 1 reduces dynamin-related protein 1 and mitochondrial fission activity
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Manczak, Maria, primary, Kandimalla, Ramesh, additional, Yin, Xiangling, additional, and Hemachandra Reddy, P, additional
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- 2018
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103. Nigrostriatal neuronal death following chronic dichlorvos exposure: crosstalk between mitochondrial impairments, α synuclein aggregation, oxidative damage and behavioral changes
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BK Binukumar, Bal Amanjit, Kandimalla Ramesh JL, and Gill Kiran
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Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background In recent years, several lines of evidence have shown an increase in Parkinson's disease prevalence in rural environments where pesticides are heavily used. Although, the underlying mechanism for neuronal degeneration in sporadic PD remains unknown, mitochondrial dysfunction, oxidative stress and proteasomal dysfunction are proposed as contributing factors. In this study rats were chronically and continuously exposed to the pesticide, dichlorvos to identify the molecular mechanism of nigrostaital neuronal degeneration. Result Chronic dichlorvos exposure (2.50 mg/kg b.wt.s.c/daily for 12 weeks) caused nigrostriatal dopaminergic degeneration. The degenerative changes were accompanied by a loss of 60-80% of the nigral dopamine neurons and 60-70% reduction in striatal dopamine and tyrosine hydroxylase levels. Dichlorvos exposed animals also showed α -synuclein and ubiquitin positive inclusions along with swollen, dystrophic neurites and mitochondrial abnormalities like decreased complex I&IV activities, increased mitochondrial size, axonal degeneration and presence of electron dense perinuclear cytoplasmic inclusions in the substantia nigra of rats. These animals also showed evidence of oxidative stress, including increased mitochondrial ROS levels, decreased MnSOD activity and increased lipid peroxidation. Measurable impairments in neurobehavioral indices were also observed. Notable exacerbations in motor impairments, open field and catalepsy were also evident in dichlorvos exposed animals. Conclusion All these findings taken together indicate that chronic dichlorvos exposure may cause nigrostaital neurodegenaration and significant behavioral impairments.
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- 2010
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104. Prevalence of the apolipoprotein E epsilon 4 allele in amyloid beta positive subjects across the spectrum of Alzheimer's disease
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Mattsson, Niklas, Mattsson, Niklas, Groot, Colin, Jansen, Willemijn J., Landau, Susan M., Villemagne, Victor L., Engelborghs, Sebastiaan, Mintun, Mark M., Lleo, Alberto, Molinuevo, Jose Luis, Jagust, William J., Frisoni, Giovanni B., Ivanoiu, Adrian, Chetelat, Gael, Oliveira, Catarina Resende, Rodrigue, Karen M., Kornhuber, Johannes, Wallin, Anders, Klimkowicz-Mrowiec, Aleksandra, Kandimalla, Ramesh, Popp, Julius, Aalten, Pauline P., Aarsland, Dag, Alcolea, Daniel, Almdahl, Ina S., Baldeiras, Ines, Buchem, Mark A., Cavedo, Enrica, Chen, Kewei, Cohen, Ann D., Foerster, Stefan, Fortea, Juan, Frederiksen, Kristian S., Freund-Levi, Yvonne, Gill, Kiran Dip, Gkatzima, Olymbia, Grimmer, Timo, Hampel, Harald, Herukka, Sanna-Kaisa, Johannsen, Peter, Laere, Koen, Leon, Mony J., Maier, Wolfgang, Marcusson, Jan, Meulenbroek, Olga, Mollergard, Hanne M., Morris, John C., Mroczko, Barbara, Nordlund, Arto, Prabhakar, Sudesh, Peters, Oliver, Rami, Lorena, Rodriguez-Rodriguez, Eloy, Roe, Catherine M., Ruther, Eckart, Santana, Isabel, Schroder, Johannes, Seo, Sang W., Soininen, Hilkka, Spiru, Luiza, Stomrud, Erik, Struyfs, Hanne, Teunissen, Charlotte E., Verhey, Frans R. J., Vos, Stephanie J. B., Doorn, Linda J. C. van Waalwijk, Waldemar, Gunhild, Wallin, Asa K., Wiltfang, Jens, Vandenberghe, Rik, Brooks, David J., Fladby, Tormod, Rowe, Christopher C., Drzezga, Alexander, Verbeek, Marcel M., Sarazin, Marie, Wolk, David A., Fleisher, Adam S., Klunk, William E., Na, Duk L., Sanchez-Juan, Pascual, Lee, Dong Young, Nordberg, Agneta, Tsolaki, Magda, Camus, Vincent, Rinne, Juha O., Fagan, Anne M., Zetterberg, Henrik, Blennow, Kaj, Rabinovici, Gil D., Hansson, Oskar, Berckel, Bart N. M., Flier, Wiesje M., Scheltens, Philip, Visser, Pieter Jelle, Ossenkoppele, Rik, Mattsson, Niklas, Mattsson, Niklas, Groot, Colin, Jansen, Willemijn J., Landau, Susan M., Villemagne, Victor L., Engelborghs, Sebastiaan, Mintun, Mark M., Lleo, Alberto, Molinuevo, Jose Luis, Jagust, William J., Frisoni, Giovanni B., Ivanoiu, Adrian, Chetelat, Gael, Oliveira, Catarina Resende, Rodrigue, Karen M., Kornhuber, Johannes, Wallin, Anders, Klimkowicz-Mrowiec, Aleksandra, Kandimalla, Ramesh, Popp, Julius, Aalten, Pauline P., Aarsland, Dag, Alcolea, Daniel, Almdahl, Ina S., Baldeiras, Ines, Buchem, Mark A., Cavedo, Enrica, Chen, Kewei, Cohen, Ann D., Foerster, Stefan, Fortea, Juan, Frederiksen, Kristian S., Freund-Levi, Yvonne, Gill, Kiran Dip, Gkatzima, Olymbia, Grimmer, Timo, Hampel, Harald, Herukka, Sanna-Kaisa, Johannsen, Peter, Laere, Koen, Leon, Mony J., Maier, Wolfgang, Marcusson, Jan, Meulenbroek, Olga, Mollergard, Hanne M., Morris, John C., Mroczko, Barbara, Nordlund, Arto, Prabhakar, Sudesh, Peters, Oliver, Rami, Lorena, Rodriguez-Rodriguez, Eloy, Roe, Catherine M., Ruther, Eckart, Santana, Isabel, Schroder, Johannes, Seo, Sang W., Soininen, Hilkka, Spiru, Luiza, Stomrud, Erik, Struyfs, Hanne, Teunissen, Charlotte E., Verhey, Frans R. J., Vos, Stephanie J. B., Doorn, Linda J. C. van Waalwijk, Waldemar, Gunhild, Wallin, Asa K., Wiltfang, Jens, Vandenberghe, Rik, Brooks, David J., Fladby, Tormod, Rowe, Christopher C., Drzezga, Alexander, Verbeek, Marcel M., Sarazin, Marie, Wolk, David A., Fleisher, Adam S., Klunk, William E., Na, Duk L., Sanchez-Juan, Pascual, Lee, Dong Young, Nordberg, Agneta, Tsolaki, Magda, Camus, Vincent, Rinne, Juha O., Fagan, Anne M., Zetterberg, Henrik, Blennow, Kaj, Rabinovici, Gil D., Hansson, Oskar, Berckel, Bart N. M., Flier, Wiesje M., Scheltens, Philip, Visser, Pieter Jelle, and Ossenkoppele, Rik
- Abstract
Introduction: Apolipoprotein E (APOE) epsilon 4 is the major genetic risk factor for Alzheimer's disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid beta(A beta) pathology. Methods: We included 3451 A beta+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE epsilon 4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE epsilon 4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in A beta+ cognitively normal and A beta+ mild cognitive impairment (P <.05) but not in A beta+ AD dementia (P =.66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE E4 prevalence in AD was higher than that in previous studies, which did not require presence of A beta pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location. (C) 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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- 2018
105. Imaging and curcumin delivery in pancreatic cancer cell lines using PEGylated α-Gd2(MoO4)3mesoporous particles
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Jae Su Yu, Kandimalla Ramesh, G. Seeta Rama Raju, Ganji Purnachandra Nagaraju, Bassel F. El-Rayes, and Eluri Pavitra
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Curcumin ,Metal Nanoparticles ,Nanoparticle ,Gadolinium ,Polyethylene Glycols ,Inorganic Chemistry ,chemistry.chemical_compound ,Coordination Complexes ,Cell Line, Tumor ,Humans ,Particle Size ,Cell Proliferation ,Drug Carriers ,Microscopy, Confocal ,Nucleoplasm ,Chemistry ,In vitro ,Pancreatic Neoplasms ,Biochemistry ,Cytoplasm ,Drug delivery ,Biophysics ,Mesoporous material ,Porosity ,Intracellular - Abstract
Mesoporous particles are emerging as multifunctional biomaterials for imaging and drug delivery in several disease models, including cancer. We developed PEGylated α-Gd2(MoO4)3 marigold flower-like mesoporous particles for the purpose of drug delivery and, more specifically, evaluated their ability to deliver curcumin. The obtained mesoporous particles significantly conjugated the curcumin particles on their surfaces by inducing the formation of curcumin nanoparticles. In vitro studies of the PEGylated mesoporous particles filled with curcumin demonstrated that these particles could considerably facilitate the continuous and sustained release of curcumin into the cytoplasm and nucleus. As a result, the intracellular release of curcumin can inhibit proliferation in two human pancreatic cancer cell lines: MIA PaCa-2 and PANC-1. Additionally, the particles showed the increased inhibition of pIKKα, pIKKα/β and NF-κB-DNA binding activity as compared to pure curcumin. The curcumin conjugated mesoporous particles are concentrated in the cytoplasm and nucleus of the treated cancer cell lines. Consequently, these mesoporous particles are an effective method for drug delivery that can cross the biological barriers of the body targeting the cellular nucleoplasm.
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- 2014
106. Mitochondrial division inhibitor 1 reduces dynamin-related protein 1 and mitochondrial fission activity
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Manczak, Maria, primary, Kandimalla, Ramesh, additional, Yin, Xiangling, additional, and Reddy, P Hemachandra, additional
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- 2018
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107. Conformational transition pathway of R308K mutant glucokinase in the presence of the glucokinase activator YNKGKA 4
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Yellapu, Nanda Kumar, primary, Kandlapalli, Kalpana, additional, Kandimalla, Ramesh, additional, and Adi, Pradeepkiran Jangampalli, additional
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- 2018
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108. Hippocampal mutant APP and amyloid beta-induced cognitive decline, dendritic spine loss, defective autophagy, mitophagy and mitochondrial abnormalities in a mouse model of Alzheimer’s disease
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Manczak, Maria, primary, Kandimalla, Ramesh, additional, Yin, Xiangling, additional, and Reddy, P Hemachandra, additional
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- 2018
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109. Protective Effects of Indian Spice Curcumin Against Amyloid-β in Alzheimer’s Disease
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Reddy, P. Hemachandra, primary, Manczak, Maria, additional, Yin, Xiangling, additional, Grady, Mary Catherine, additional, Mitchell, Andrew, additional, Tonk, Sahil, additional, Kuruva, Chandra Sekhar, additional, Bhatti, Jasvinder Singh, additional, Kandimalla, Ramesh, additional, Vijayan, Murali, additional, Kumar, Subodh, additional, Wang, Rui, additional, Pradeepkiran, Jangampalli Adi, additional, Ogunmokun, Gilbert, additional, Thamarai, Kavya, additional, Quesada, Kandi, additional, Boles, Annette, additional, and Reddy, Arubala P., additional
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- 2018
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110. Hippocampal phosphorylated tau induced cognitive decline, dendritic spine loss and mitochondrial abnormalities in a mouse model of Alzheimer’s disease
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Kandimalla, Ramesh, primary, Manczak, Maria, additional, Yin, Xiangling, additional, Wang, Rui, additional, and Reddy, P Hemachandra, additional
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- 2017
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111. Cell cycle activation in p21 dependent pathway: An alternative mechanism of organophosphate induced dopaminergic neurodegeneration
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Wani, Willayat Yousuf, primary, Kandimalla, Ramesh J.L., additional, Sharma, Deep Raj, additional, Kaushal, Alka, additional, Ruban, Anand, additional, Sunkaria, Aditya, additional, Vallamkondu, Jayalakshmi, additional, Chiarugi, Alberto, additional, Reddy, P. Hemachandra, additional, and Gill, Kiran Dip, additional
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- 2017
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112. Is Alzheimer's disease a Type 3 Diabetes? A critical appraisal
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Kandimalla, Ramesh, primary, Thirumala, Vani, additional, and Reddy, P. Hemachandra, additional
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- 2017
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113. Dynamics of diabetes and obesity: Epidemiological perspective
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Boles, Annette, primary, Kandimalla, Ramesh, additional, and Reddy, P. Hemachandra, additional
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- 2017
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114. Therapeutics of Neurotransmitters in Alzheimer’s Disease
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Kandimalla, Ramesh, primary and Reddy, P. Hemachandra, additional
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- 2017
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115. Mitochondria-targeted small molecule SS31: a potential candidate for the treatment of Alzheimer’s disease
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Reddy, P. Hemachandra, primary, Manczak, Maria, additional, and Kandimalla, Ramesh, additional
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- 2017
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116. Novel 1, 4-dihydropyridines for L-type calcium channel as antagonists for cadmium toxicity
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Saddala, Madhu Sudhana, primary, Kandimalla, Ramesh, additional, Adi, Pradeepkiran Jangampalli, additional, Bhashyam, Sainath Sri, additional, and Asupatri, Usha Rani, additional
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- 2017
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117. A critical evaluation of neuroprotective and neurodegenerative MicroRNAs in Alzheimer's disease
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Reddy, P. Hemachandra, primary, Tonk, Sahil, additional, Kumar, Subodh, additional, Vijayan, Murali, additional, Kandimalla, Ramesh, additional, Kuruva, Chandra Sekhar, additional, and Reddy, Arubala P., additional
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- 2017
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118. Protective Effects of a Natural Product, Curcumin, against Amyloid β Induced Mitochondrial and Synaptic Toxicities in Alzheimer'S Disease
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Reddy, P Hemachandra, primary, Manczak, Maria, additional, Yin, Xiangling, additional, Grady, Mary Catharine, additional, Mitchell, Andrew, additional, Kandimalla, Ramesh, additional, and Kuruva, Chandra Sekhar, additional
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- 2016
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119. Prevalence of cerebral amyloid pathology in persons without dementia
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Jansen, Willemijn J., Ossenkoppele, Rik, Knol, Dirk L., Tijms, Betty M., Scheltens, Philip, Verhey, Frans R. J., Visser, Pieter Jelle, Aalten, Pauline, Aarsland, Dag, Alcolea, Daniel, Alexander, Myriam, Roe, Catherine M., Rot, Uros, Rowe, Christopher C., Rüther, Eckart, Sabri, Osama, Sanchez-Juan, Páscual, Santana, Isabel, Sarazin, Marie, Schröder, Johannes, Schütte, Christin, Almdahl, Ina S., Seo, Sang W., Soetewey, Femke, Soininen, Hilkka, Spiru, Luiza, Struyfs, Hanne, Teunissen, Charlotte E., Tsolaki, Magda, Vandenberghe, Rik, Verbeek, Marcel M., Villemagne, Victor L., Arnold, Steven E., Vos, Stephanie J. B., van Waalwijk van Doorn, Linda J. C., Waldemar, Gunhild, Wallin, Anders, Wallin, Åsa K., Wiltfang, Jens, Wolk, David A., Zboch, Marzena, Zetterberg, Henrik, Baldeiras, Inês, Barthel, Henryk, van Berckel, Bart N. M., Bibeau, Kristen, Blennow, Kaj, Brooks, David J., van Buchem, Mark A., Camus, Vincent, Cavedo, Enrica, Chen, Kewei, Chetelat, Gael, Cohen, Ann D., Drzezga, Alexander, Engelborghs, Sebastiaan, Fagan, Anne M., Fladby, Tormod, Fleisher, Adam S., van der Flier, Wiesje M., Ford, Lisa, Förster, Stefan, Fortea, Juan, Foskett, Nadia, Frederiksen, Kristian S., Freund-Levi, Yvonne, Frisoni, Giovanni B., Froelich, Lutz, Gabryelewicz, Tomasz, Gill, Kiran Dip, Gkatzima, Olymbia, Gómez-Tortosa, Estrella, Gordon, Mark Forrest, Grimmer, Timo, Hampel, Harald, Hausner, Lucrezia, Hellwig, Sabine, Herukka, Sanna-Kaisa, Hildebrandt, Helmut, Ishihara, Lianna, Ivanoiu, Adrian, Jagust, William J., Johannsen, Peter, Kandimalla, Ramesh, Kapaki, Elisabeth, Klimkowicz-Mrowiec, Aleksandra, Klunk, William E., Köhler, Sebastian, Koglin, Norman, Kornhuber, Johannes, Kramberger, Milica G., Van Laere, Koen, Landau, Susan M., Lee, Dong Young, de Leon, Mony, Lisetti, Viviana, Lleó, Alberto, Madsen, Karine, Maier, Wolfgang, Marcusson, Jan, Mattsson, Niklas, De Mendonça, Alexandre, Meulenbroek, Olga, Meyer, Philipp T., Mintun, Mark A., Mok, Vincent, Molinuevo, José Luis, Møllergård, Hanne M., Morris, John C., Mroczko, Barbara, Van der Mussele, Stefan, Na, Duk L., Newberg, Andrew, Nordberg, Agneta, Nordlund, Arto, Novak, Gerald P., Paraskevas, George P., Parnetti, Lucilla, Perera, Gayan, Peters, Oliver, Popp, Julius, Prabhakar, Sudesh, Rabinovici, Gil D., Ramakers, Inez H. G. B., Rami, Lorena, Resende de Oliveira, Catarina, Rinne, Juha O., Rodrigue, Karen M., Rodríguez-Rodríguez, Eloy, and Repositório da Universidade de Lisboa
- Abstract
Copyright © 2015 American Medical Association. All rights reserved., Importance: Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies. Objective: To use individual participant data meta-analysis to estimate the prevalence of amyloid pathology as measured with biomarkers in participants with normal cognition, subjective cognitive impairment (SCI), or mild cognitive impairment (MCI). Data sources: Relevant biomarker studies identified by searching studies published before April 2015 using the MEDLINE and Web of Science databases and through personal communication with investigators. Study selection: Studies were included if they provided individual participant data for participants without dementia and used an a priori defined cutoff for amyloid positivity. Data extraction and synthesis: Individual records were provided for 2914 participants with normal cognition, 697 with SCI, and 3972 with MCI aged 18 to 100 years from 55 studies. Main outcomes and measures: Prevalence of amyloid pathology on positron emission tomography or in cerebrospinal fluid according to AD risk factors (age, apolipoprotein E [APOE] genotype, sex, and education) estimated by generalized estimating equations. Results: The prevalence of amyloid pathology increased from age 50 to 90 years from 10% (95% CI, 8%-13%) to 44% (95% CI, 37%-51%) among participants with normal cognition; from 12% (95% CI, 8%-18%) to 43% (95% CI, 32%-55%) among patients with SCI; and from 27% (95% CI, 23%-32%) to 71% (95% CI, 66%-76%) among patients with MCI. APOE-ε4 carriers had 2 to 3 times higher prevalence estimates than noncarriers. The age at which 15% of the participants with normal cognition were amyloid positive was approximately 40 years for APOE ε4ε4 carriers, 50 years for ε2ε4 carriers, 55 years for ε3ε4 carriers, 65 years for ε3ε3 carriers, and 95 years for ε2ε3 carriers. Amyloid positivity was more common in highly educated participants but not associated with sex or biomarker modality. Conclusions and relevance: Among persons without dementia, the prevalence of cerebral amyloid pathology as determined by positron emission tomography or cerebrospinal fluid findings was associated with age, APOE genotype, and presence of cognitive impairment. These findings suggest a 20- to 30-year interval between first development of amyloid positivity and onset of dementia., The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement No. 115372, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in-kind contribution. BIOMARKAPD is an EU Joint Programme–Neurodegenerative Disease Research (JPND) project. The project is supported through national funding organizations under the aegis of JPND (http://www.jpnd.eu). In the Netherlands, this is ZonMw. The DESCRIPA study was funded by the European Commission within the 5th framework program (QLRT-2001-2455). The EDAR study was funded by the European Commission as part of the 6th framework programme (contract No. 37670). This research was performed within the framework of the Center for Translational Molecular Medicine (CTTM) (http://www.ctmm.nl), project LeARN (grant 02N-101). The AIBL study was funded in part by the study partners (Australian Commonwealth Scientific Industrial and Research Organization [CSIRO], Edith Cowan University [ECU], Mental Health Research Institute [MHRI], Alzheimer’s Australia [AA], National Ageing Research Institute [NARI], Austin Health, CogState, Hollywood Private Hospital, Sir Charles Gardner Hospital). The study also received support from the National Health and Medical Research Council (NHMRC) and the Dementia Collaborative Research Centres program (DCRC2), as well as ongoing funding from the Science and Industry Endowment Fund (SIEF). Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health grant U01 AG024904) and the US Department of Defense ADNI (W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging and the National Institute of Biomedical Imaging and Bioengineering and through generous contributions from the following: Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; BioClinica; Biogen Idec; Bristol-Myers Squibb Company; Eisai; Elan Pharmaceuticals; Eli Lilly; F. Hoffmann-La Roche and its affiliated company Genentech; GE Healthcare; Innogenetics; IXICO; Janssen Alzheimer Immunotherapy Research & Development; Johnson & Johnson Pharmaceutical Research & Development; Medpace; Merck; Meso Scale Diagnostics; NeuroRx Research; Novartis Pharmaceuticals; Pfizer; Piramal Imaging; Servier; Synarc; and Takeda Pharmaceutical. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (http://www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. The Dementia Competence Network (DCN) has been supported by a grant from the German Federal Ministry of Education and Research (BMBF): Kompetenznetz Demenzen (01GI0420). Additional funding related to the randomized clinical trials came from Janssen-Cilag and Merz Pharmaceuticals. The latter funds were exclusively used for personnel, pharmaceuticals, blistering and shipment of medication, and monitoring and as capitation fees for recruiting centers. Funding source for the Chandigarh study is the Indian Council of Medical Research (ICMR), India. Funding for the St Louis contribution was provided by the National Institute on Aging (P50 AG005681, P01 AG003991, and P01 AG026276); Fred Simmons and Olga Mohan, and the Charles and Joanne Knight Alzheimer’s Research Initiative of the Washington University Knight Alzheimer’s Disease Research Center. The Tours study received financial support of the French Ministry of Health grant PHRC-N 2008 1004 and the EC-FP6-project DiMI, LSHB-CT-2005-512146. The Caen study was funded by Agence Nationale de la Recherche, Programme Hospitalier de Recherche Clinique, Région Basse Normandie, and Institut National de la Santé et de la Recherche Médicale (Inserm). The research leading to the Munich contribution to the Mattsson multicenter study has received funding from the program “Investissements d’avenir” (ANR-10-IAIHU-06). The study from Pittsburgh was supported by National Institutes of Health grants (P50 AG005133, R37 AG025516, P01 AG025204). The New York contributions to the Mattsson multicenter study were in part supported by P30 AG008051, R01 AG13616, R01 AG022374, and R01 AG12101. Data from Brescia in this article were collected by Translational Outpatient Memory Clinic (TOMC) working group at IRCCS Fatebenefratelli in Brescia, Italy. Contributors to the TOMC are G. Amicucci, S. Archetti, L. Benussi, G. Binetti, L. Bocchio-Chiavetto, C. Bonvicini, E. Canu, F. Caobelli, E. Cavedo, E. Chittò, M. Cotelli, M. Gennarelli, S. Galluzzi, C. Geroldi, R. Ghidoni, R. Giubbini, U. P. Guerra, G. Kuffenschin, G. Lussignoli, D. Moretti, B. Paghera, M. Parapini, C. Porteri, M. Romano, S. Rosini, I. Villa, R. Zanardini, and O. Zanetti. The JPND Project is supported in Italy by the Italian Ministry of Health. The assembling of the TU Munich data set was supported in part by the German research foundation (Deutsche Forschungsgemeinschaft) (HE 4560/1-2, DR 445/3-1 and DR 445/4-1 to A.D.), and by a KKF grant for clinical research of the Technische Universität München (to A.D. and T.G.). The Florbetaben phase 2 study from which data were derived for this multicenter evaluation was sponsored by Bayer Healthcare/Piramal Imaging (Berlin, Germany). This work was supported by the University of Antwerp Research Fund; the Alzheimer Research Foundation (SAO-FRA); the Research Foundation Flanders (FWO); the Agency for Innovation by Science and Technology (IWT); the Belgian Science Policy Office Interuniversity Attraction Poles (IAP) program; and the Flemish Government–initiated Methusalem excellence grant.
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- 2015
120. Mitochondrial division inhibitor 1 reduces dynamin-related protein 1 and mitochondrial fission activity.
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Manczak, Maria, Kandimalla, Ramesh, Yin, Xiangling, and Reddy, P Hemachandra
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- 2019
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121. Questions concerning the proximal origin of SARS‐CoV‐2.
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Seyran, Murat, Pizzol, Damiano, Adadi, Parise, El‐Aziz, Tarek M. A., Hassan, Sk. Sarif, Soares, Antonio, Kandimalla, Ramesh, Lundstrom, Kenneth, Tambuwala, Murtaza, Aljabali, Alaa A. A., Lal, Amos, Azad, Gajendra K., Choudhury, Pabitra P., Uversky, Vladimir N., Sherchan, Samendra P., Uhal, Bruce D., Rezaei, Nima, and Brufsky, Adam M.
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SARS-CoV-2 - Abstract
Keywords: coronavirus; fusion protein; genetic variability; mutation EN coronavirus fusion protein genetic variability mutation 1204 1206 3 01/30/21 20210301 NES 210301 SUMMARY There is a consensus that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated naturally from bat coronaviruses (CoVs), in particular RaTG13. However, the SARS-CoV-2 host tropism/adaptation pattern has significant discrepancies compared with other CoVs, raising questions concerning the proximal origin of SARS-CoV-2. Similarly, the S protein receptor-binding domain (RBD) of SARS-CoV-2 has not accumulated high-frequency nonsynonymous substitutions, differentiating SARS-CoV-2 from other CoVs that have positive selection/adaptation mutations in their RBDs. [Extracted from the article]
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- 2021
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122. Protective effects of reduced dynamin-related protein 1 against amyloid beta-induced mitochondrial dysfunction and synaptic damage in Alzheimer’s disease
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Manczak, Maria, primary, Kandimalla, Ramesh, additional, Fry, David, additional, Sesaki, Hiromi, additional, and Reddy, P. Hemachandra, additional
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- 2016
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123. Reduced dynamin-related protein 1 protects against phosphorylated Tau-induced mitochondrial dysfunction and synaptic damage in Alzheimer’s disease
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Kandimalla, Ramesh, primary, Manczak, Maria, additional, Fry, David, additional, Suneetha, Yeguvapalli, additional, Sesaki, Hiromi, additional, and Reddy, P. Hemachandra, additional
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- 2016
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124. Multiple faces of dynamin-related protein 1 and its role in Alzheimer's disease pathogenesis
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Kandimalla, Ramesh, primary and Reddy, P. Hemachandra, additional
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- 2016
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125. The Y2 receptor antagonist BIIE0246 reverses corticosterone-induced anxiogenic-related behavior and neuronal hypertrophy
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Morales-Medina, Julio César, primary, Juarez, Ismael, additional, Dominguez-Lopez, Sergio, additional, Kandimalla, Ramesh, additional, Gobbi, Gabriella, additional, Flores, Gonzalo, additional, and Quirion, Rémi, additional
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- 2016
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126. Understanding Aspects of Aluminum Exposure in Alzheimer's Disease Development
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Kandimalla, Ramesh, primary, Vallamkondu, Jayalakshmi, additional, Corgiat, Edwin B, additional, and Gill, Kiran Dip, additional
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- 2015
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127. Hippocampal phosphorylated tau induced cognitive decline, dendritic spine loss and mitochondrial abnormalities in a mouse model of Alzheimer's disease.
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Kandimalla, Ramesh, Manczak, Maria, Xiangling Yin, Rui Wang, and Reddy, P. Hemachandra
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- 2018
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128. Garrison Institute on Aging: A New Hope for Elderly Individuals and Patients with Alzheimer’s Disease
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Reddy, P. Hemachandra, primary, Blackmon, Joan, additional, Molinar-Lopez, Veronica, additional, Ament, Clay, additional, Manczak, Maria, additional, Kandimalla, Ramesh, additional, Yin, Xianglin, additional, Pandey, Akhilesh, additional, Kuruva, Chandra Sekhar, additional, Wang, Rui, additional, Fry, David, additional, Osborn, Carrah, additional, Stonum, Kathleen, additional, Quesada, Kandi, additional, Gonzales, Ruben, additional, and Boles, Annette, additional
- Published
- 2015
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129. MRI-Based Classification Models in Prediction of Mild Cognitive Impairment and Dementia in Late-Life Depression.
- Author
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Lebedeva, Aleksandra K., Westman, Eric, Borza, Tom, Beyer, Mona K., Engedal, Knut, Aarsland, Dag, Selbaek, Geir, Haberg, Asta K., Watt, Douglas, and Kandimalla, Ramesh
- Subjects
DEPRESSION in old age ,DEMENTIA ,MAGNETIC resonance imaging ,MILD cognitive impairment ,HYPOTHALAMUS - Abstract
Objective: Late-life depression (LLD) is associated with development of different types of dementia. Identification of LLD patients, who will develop cognitive decline, i.e., the early stage of dementia would help to implement interventions earlier. The purpose of this study was to assess whether structural brain magnetic resonance imaging (MRI) in LLD patients can predict mild cognitive impairment (MCI) or dementia 1 year prior to the diagnosis. Methods: LLD patients underwent brain MRI at baseline and repeated clinical assessment after 1-year. Structural brain measurements were obtained using Freesurfer software (v. 5.1) from the T1W brain MRI images. MRI-based Random Forest classifier was used to discriminate between LLD who developed MCI or dementia after 1-year follow-up and cognitively stable LLD. Additionally, a previously established Random Forest model trained on 185 patients with Alzheimer's disease (AD) vs. 225 cognitively normal elderly from the Alzheimer's disease Neuroimaging Initiative was tested on the LLD data set (ADNI model). Results: MCI and dementia diagnoses were predicted in LLD patients with 76%/68%/84% accuracy/sensitivity/specificity. Adding the baseline Mini-Mental State Examination (MMSE) scores to the models improved accuracy/sensitivity/specificity to 81%/75%/86%. The best model predicted MCI status alone using MRI and baseline MMSE scores with accuracy/sensitivity/specificity of 89%/85%/90%. The most important region for all the models was right ventral diencephalon, including hypothalamus. Its volume correlated negatively with the number of depressive episodes. ADNI model trained on AD vs. Controls using SV could predict MCI-DEM patients with 67% accuracy. Conclusion: LDD patients developing MCI and dementia can be discriminated from LLD patients remaining cognitively stable with good accuracy based on baseline structural MRI alone. Baseline MMSE score improves prediction accuracy. Ventral diencephalon, including the hypothalamus might play an important role in preservation of cognitive functions in LLD. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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130. Effort Not Speed Characterizes Comprehension of Spoken Sentences by Older Adults with Mild Hearing Impairment.
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Ayasse, Nicole D., Lash, Amanda, Wingfield, Arthur, Kandimalla, Ramesh, and Jingwen Niu
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COMPREHENSION ,HEARING disorders ,ORAL communication ,SENTENCES (Grammar) ,COGNITIVE ability ,HEALTH of older people - Abstract
In spite of the rapidity of everyday speech, older adults tend to keep up relatively well in day-to-day listening. In laboratory settings older adults do not respond as quickly as younger adults in off-line tests of sentence comprehension, but the question is whether comprehension itself is actually slower. Two unique features of the human eye were used to address this question. First, we tracked eye-movements as 20 young adults and 20 healthy older adults listened to sentences that referred to one of four objects pictured on a computer screen. Although the older adults took longer to indicate the referenced object with a cursor-pointing response, their gaze moved to the correct object as rapidly as that of the younger adults. Second, we concurrently measured dilation of the pupil of the eye as a physiological index of effort. This measure revealed that although poorer hearing acuity did not slow processing, success came at the cost of greater processing effort. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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131. Changes in Neural Activity Underlying Working Memory after Computerized Cognitive Training in Older Adults.
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Tusch, Erich S., Alperin, Brittany R., Ryan, Eliza, Holcomb, Phillip J., Mohammed, Abdul H., Daffner, d. Kirk R., Kandimalla, Ramesh, and Lorenzo-López, Laura
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COGNITIVE training ,COGNITIVE ability ,COGNITIVE learning ,SHORT-term memory ,AGING - Abstract
Computerized cognitive training (CCT) may counter the impact of aging on cognition, but both the efficacy and neurocognitive mechanisms underlying CCT remain controversial. In this study, 35 older individuals were randomly assigned to Cogmed adaptive working memory (WM) CCT or an active control CCT, featuring five weeks of five 40 min sessions per week. Before and after the 5-week intervention, event-related potentials were measured while subjects completed a visual n-back task with three levels of demand (0-back, 1-back, 2-back). The anterior P3a served as an index of directing attention and the posterior P3b as an index of categorization/WM updating. We hypothesized that adaptive CCT would be associated with decreased P3 amplitude at low WM demand and increased P3 amplitude at high WM demand. The adaptive CCT group exhibited a training-related increase in the amplitude of the anterior P3a and posterior P3b in response to target stimuli across n-back tasks, while subjects in the active control CCT group demonstrated a post-training decrease in the anterior P3a. Performance did not differ between groups or sessions. Larger overall P3 amplitudes were strongly associated with better task performance. Increased post- CCT P3 amplitude correlated with improved task performance; this relationship was especially robust at high task load. Our findings suggest that adaptive WM training was associated with increased orienting of attention, as indexed by the P3a, and the enhancement of categorization/WM updating processes, as indexed by the P3b. Increased P3 amplitude was linked to improved performance; however. there was no direct association between adaptive training and improved performance. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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132. CSF p-Tau levels in the prediction of Alzheimer's disease
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Kandimalla, Ramesh J. L., primary, Prabhakar, Sudesh, additional, Wani, Willayat Yousuf, additional, Kaushal, Alka, additional, Gupta, Nidhi, additional, Sharma, Deep Raj, additional, Grover, V. K., additional, Bhardwaj, Neerja, additional, Jain, Kajal, additional, and Gill, Kiran Dip, additional
- Published
- 2013
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133. PEGylated α-Gd2(MoO4)3 Mesoporous Flowers: Synthesis, Characterization, and Biological Application
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Seeta Rama Raju, G., primary, Pavitra, E., additional, Nagaraju, Ganji Purnachandra, additional, Kandimalla, Ramesh, additional, El-Rayes, Bassel F., additional, and Yu, Jae Su, additional
- Published
- 2013
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134. Apolipoprotein E Levels in the Cerebrospinal Fluid of North Indian Patients With Alzheimer’s Disease
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Kandimalla, Ramesh J. L., primary, Wani, Willayat Yousuf, additional, Anand, R., additional, Kaushal, Alka, additional, Prabhakar, Sudesh, additional, Grover, Vinod K., additional, Bharadwaj, Neerja, additional, Jain, Kajal, additional, and Gill, Kiran Dip, additional
- Published
- 2013
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135. Effect of Resveratrol and Nicotine on PON1 Gene Expression: In Vitro Study
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Gupta, Nidhi, primary, Kandimalla, Ramesh, additional, Priyanka, Kumari, additional, Singh, Gagandip, additional, Gill, Kiran Dip, additional, and Singh, Surjit, additional
- Published
- 2013
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136. Dual Tasking for the Differentiation between Depression and Mild Cognitive Impairment.
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Metzger, Florian G., Hobert, Markus A., Ehlis, Ann-Christine, Hasmann, Sandra E., Tim Hahn, Eschweiler, Gerhard W., Berg, Daniela, Fallgatter, Andreas J., Maetzler, Walter, Morganti, Francesca, and Kandimalla, Ramesh
- Subjects
MENTAL depression ,MILD cognitive impairment ,ALZHEIMER'S disease ,NEURODEGENERATION ,AGE factors in disease - Abstract
Differentiation of mild cognitive impairment from depression in elderly adults is a clinically relevant issue which is not sufficiently solved. Gait and dual task (DT) parameters may have the potential to complement current diagnostic work-up, as both dementia and depression are associated with changes of gait and DT parameters. Methods: Seven hundred and four participants of the TREND study (Tübinger evaluation of Risk factors for Early detection of NeuroDegeneration) aged 50-80 years were assessed using the Consortium to Establish a Registry for Alzheimer's Disease Plus test battery for testing cognition and Beck's Depression Inventory for evaluation of depression. Based on these results, four groups were defined: acute depressed (N = 53), cognitively mildly impaired (N = 97), acute depressed, and cognitively mildly impaired (N = 15), and controls (N = 536). Participants underwent a 20m walk and checking boxes task under single (ST) and DT conditions. ST and DT performance and dual task costs (DTC) were calculated. Due to the typical age of increasing incidence of depressive and also cognitive symptoms, the 7th decade was calculated separately. Results: ST speeds of gait and checking boxes, DT walking speed, and walking DTC were significantly different between groups. Healthy controls were the fastest in all paradigms and cognitively mildly impaired had higher DTC than depressed individuals. Additionally, we constructed a multivariate predictive model differentiating the groups on a single-subject level. Conclusion: DT parameters are simply and comfortably measureable, and DTC can easily be determined. The combination of these parameters allows a differentiation of depressed and cognitively mildly impaired elderly adults. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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137. Association of Cerebral Amyloidosis, Blood Pressure, and Neuronal Injury with Late-Life Onset Depression.
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Min Soo Byun, Young Min Choe, Bo Kyung Sohn, Dahyun Yi, Ji Young Han, Jinsick Park, Hyo Jung Choi, Hyewon Baek, Jun Ho Lee, Hyun Jung Kim, Yu Kyeong Kim, Eun Jin Yoon, Chul-Ho Sohn, Jong Inn Woo, Dong Young Lee, Yu-Min Kuo, and Kandimalla, Ramesh
- Subjects
AMYLOIDOSIS ,BLOOD pressure ,NERVOUS system injuries ,ALZHEIMER'S disease ,MENTAL depression ,MILD cognitive impairment - Abstract
Previous literature suggests that Alzheimer's disease (AD) process may contribute to late-life onset depression (LLOD). Therefore, we investigated the association of LLOD with cerebral amyloidosis and neuronal injury, the two key brain changes in AD, along with vascular risks. Twenty nine non-demented individuals who first experienced major depressive disorder (MDD) after age of 60 years were included as LLOD subjects, and 27 non-demented elderly individuals without lifetime experience of MDD were included as normal controls (NC). Comorbid mild cognitive impairment (MCI) was diagnosed in 48% of LLOD subjects and in 0% of NC. LLOD, irrespective of comorbid MCI diagnosis, was associated with prominent prefrontal cortical atrophy. Compared to NC, LLOD subjects with comorbid MCI (LLOD
MCI ) showed increased cerebral11 C-Pittsburg compound B (PiB) retention and plasma beta-amyloid 1-40 and 1-42 peptides, as measures of cerebral amyloidosis; and, such relationship was not observed in overall LLOD or LLOD without MCI (LLODwoMCI ). LLOD subjects, particularly the LLODwoMCI, had higher systolic blood pressure (SBP) than NC. When analyzed in the same multiple logistic regression model that included prefrontal gray matter (GM) density, cerebral amyloidosis, and SBP as independent variables, only prefrontal GM density showed a significant independent association with LLOD regardless of MCI comorbidity status. Our findings suggest AD process might be related to LLOD via prefrontal neuronal injury in the MCI stage, whereas vascular processes--SBP elevation, in particular--are associated with LLOD via prefrontal neuronal injury even in cognitively intact or less impaired individuals. [ABSTRACT FROM AUTHOR]- Published
- 2016
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138. A Triple Network Connectivity Study of Large-Scale Brain Systems in Cognitively Normal APOE4 Carriers.
- Author
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Xia Wu, Qing Li, Xinyu Yu, Kewei Chen, Fleisher, Adam S., Xiaojuan Guo, Jiacai Zhang, Reiman, Eric M., Li Yao, Rui Li, Kandimalla, Ramesh, and Sehgal, Neha
- Subjects
NEURAL circuitry ,APOLIPOPROTEIN E ,BRAIN diseases ,INDEPENDENT component analysis ,PATHOLOGICAL psychology ,DISEASE risk factors - Abstract
The triple network model, consisting of the central executive network (CEN), salience network (SN) and default mode network (DMN), has been recently employed to understand dysfunction in core networks across various disorders. Here we used the triple network model to investigate the large-scale brain networks in cognitively normal apolipoprotein e4 (APOE4) carriers who are at risk of Alzheimer's disease (AD). To explore the functional connectivity for each of the three networks and the effective connectivity among them, we evaluated 17 cognitively normal individuals with a family history of AD and at least one copy of the APOE4 allele and compared the findings to those of 12 individuals who did not carry the APOE4 gene or have a family history of AD, using independent component analysis (ICA) and Bayesian network (BN) approach. Our findings indicated altered within-network connectivity that suggests future cognitive decline risk, and preserved between-network connectivity that may support their current preserved cognition in the cognitively normal APOE4 allele carriers. The study provides novel sights into our understanding of the risk factors for AD and their influence on the triple network model of major psychopathology. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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139. Plasma Clusterin and the CLU Gene rs11136000 Variant Are Associated with Mild Cognitive Impairment in Type 2 Diabetic Patients.
- Author
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Rongrong Cai, Jing Han, Jie Sun, Rong Huang, Sai Tian, Yanjue Shen, Xue Dong, Wenqing Xia, Shaohua Wang, Kandimalla, Ramesh, and Vijayan, Murali
- Subjects
MILD cognitive impairment ,CLUSTERIN ,TYPE 2 diabetes ,NEUROPSYCHOLOGY ,SINGLE nucleotide polymorphisms - Abstract
Objective: Type 2 diabetes mellitus (T2DM) is related to an elevated risk of mild cognitive impairment (MCI). Plasma clusterin is reported associated with the early pathology of Alzheimer's disease (AD) and longitudinal brain atrophy in subjects with MCI. The rs11136000 single nucleotide polymorphism within the clusterin (CLU) gene is also associated with the risk of AD. We aimed to investigate the associations among plasma clusterin, rs11136000 genotype and T2DM-associated MCI. Methods: A total of 231 T2DM patients, including 126 MCI and 105 cognitively healthy controls were enrolled in this study. Demographic parameters were collected and neuropsychological tests were conducted. Plasma clusterin and CLU rs11136000 genotype were examined. Results: Plasma clusterin was significantly higher in MCI patients than in control group p = 0.007). In subjects with MCI, plasma clusterin level was negatively correlated with Montreal cognitive assessment and auditory verbal learning test_delayed recall scores (p = 0.027 and p = 0.020, respectively). After adjustment for age, educational attainment, and gender, carriers of rs11136000 TT genotype demonstrated reduced risk for MCI compared with the CC genotype carriers (OR = 0.158, χ² = 4.113, p = 0.043). Multivariable regression model showed that educational attainment, duration of diabetes, high-density lipoprotein cholesterol (HDL-c), and plasma clusterin levels are associated with MCI in T2DM patients. Conclusions: Plasma clusterin was associated with MCI and may reflect a protective response in T2DM patients. TT genotype exhibited a reduced risk of MCI compared to CC genotype. Further investigations should be conducted to determine the role of clusterin in cognitive decline. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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140. Mechanisms of Aβ Clearance and Degradation by Glial Cells.
- Author
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Ries, Miriam, Sastre, Magdalena, Wandosell, Francisco G., and Kandimalla, Ramesh
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NEUROGLIA ,HOMEOSTASIS ,NEURODEGENERATION ,ASTROCYTES ,APOLIPOPROTEINS - Abstract
Glial cells have a variety of functions in the brain, ranging from immune defense against external and endogenous hazardous stimuli, regulation of synaptic formation, calcium homeostasis, and metabolic support for neurons. Their dysregulation can contribute to the development of neurodegenerative disorders, including Alzheimer's disease (AD). One of the most important functions of glial cells in AD is the regulation of Amyloid-b (Aβ) levels in the brain. Microglia and astrocytes have been reported to play a central role as moderators of Aβ clearance and degradation. The mechanisms of Aβ degradation by glial cells include the production of proteases, including neprilysin, the insulin degrading enzyme, and the endothelin-converting enzymes, able to hydrolyse Aβ at different cleavage sites. Besides these enzymes, other proteases have been described to have some role in Aβ elimination, such as plasminogen activators, angiotensinconverting enzyme, and matrix metalloproteinases. Other relevant mediators that are released by glial cells are extracellular chaperones, involved in the clearance of Aβ alone or in association with receptors/transporters that facilitate their exit to the blood circulation. These include apolipoproteins, α2macroglobulin, and α1-antichymotrypsin. Finally, astrocytes and microglia have an essential role in phagocytosing Aβ, in many cases via a number of receptors that are expressed on their surface. In this review, we examine all of these mechanisms, providing an update on the latest research in this field. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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141. Melodic Contour Identification Reflects the Cognitive Threshold of Aging.
- Author
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Eunju Jeong, Hokyoung Ryu, Kandimalla, Ramesh, and Jingwen Niu
- Subjects
COGNITION disorders ,HEMODYNAMICS ,AGING ,PREFRONTAL cortex ,COGNITIVE ability - Abstract
Cognitive decline is a natural phenomenon of aging. Although there exists a consensus that sensitivity to acoustic features of music is associated with such decline, no solid evidence has yet shown that structural elements and contexts of music explain this loss of cognitive performance. This study examined the extent and the type of cognitive decline that is related to the contour identification task (CIT) using tones with different pitches (i.e., melodic contours). Both younger and older adult groups participated in the CIT given in three listening conditions (i.e., focused, selective, and alternating). Behavioral data (accuracy and response times) and hemodynamic reactions were measured using functional near-infrared spectroscopy (fNIRS). Our findings showed cognitive declines in the older adult group but with a subtle difference from the younger adult group. The accuracy of the melodic CITs given in the target-like distraction task (CIT2) was significantly lower than that in the environmental noise (CIT1) condition in the older adult group, indicating that CIT2 may be a benchmark test for age-specific cognitive decline. The fNIRS findings also agreed with this interpretation, revealing significant increases in oxygenated hemoglobin (oxyHb) concentration in the younger (p < 0.05 for Δpre - on task; p < 0.01 for Δon - post task) rather than the older adult group (n.s for Δpre - on task; n.s for Δon - post task). We further concluded that the oxyHb difference was present in the brain regions near the right dorsolateral prefrontal cortex. Taken together, these findings suggest that CIT2 (i.e., the melodic contour task in the target-like distraction) is an optimized task that could indicate the degree and type of age-related cognitive decline. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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142. Underrepresentation of African-Americans in Alzheimer's Trials: A Call for Affirmative Action.
- Author
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Shin, Jaewook, Doraiswamy, P. Murali, Kandimalla, Ramesh, and Reddy, Tejaswini Parlapalle
- Subjects
ALZHEIMER'S disease research ,CLINICAL trials ,SEGREGATION of African Americans ,PATHOLOGICAL physiology ,HEALTH of African Americans - Abstract
The author reflects on the underrepresentation of African-Americans in Alzheimer's disease (AD) trials in the U.S. It mentions that involving a greater proportion of African-Americans in AD clinical trials will allow researchers to produce more generalizable results and a better understanding of race and ethnicity-specific differences in AD pathophysiology. It states that the Alzheimer's Disease Neuroimaging Initiative (ADNI) has made major contributions in understanding of the disease.
- Published
- 2016
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143. Glycines from the APP GXXXG/GXXXA Transmembrane Motifs Promote Formation of Pathogenic Aβ Oligomers in Cells.
- Author
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Decock, Marie, Stanga, Serena, Octave, Jean-Noël, Dewachter, Ilse, Smith, Steven O., Constantinescu, Stefan N., Kienlen-Campard, Pascal, Da Cruz E. Silva, Odete A. B., and Kandimalla, Ramesh
- Subjects
GLYCINE ,AMYLOID beta-protein precursor ,OLIGOMERS ,ALZHEIMER'S disease ,NEURODEGENERATION ,DEMENTIA ,COGNITION disorders - Abstract
Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by progressive cognitive decline leading to dementia. The amyloid precursor protein (APP) is a ubiquitous type I transmembrane (TM) protein sequentially processed to generate the β-amyloid peptide (Aβ), the major constituent of senile plaques that are typical AD lesions. There is a growing body of evidence that soluble Aβ oligomers correlate with clinical symptoms associated with the disease. The Aβ sequence begins in the extracellular juxtamembrane region of APP and includes roughly half of the TM domain. This region contains GXXXG and GXXXA motifs, which are critical for both TM protein interactions and fibrillogenic properties of peptides derived from TM a-helices. Glycine-to-leucine mutations of these motifs were previously shown to affect APP processing and Aβ production in cells. However, the detailed contribution of these motifs to APP dimerization, their relation to processing, and the conformational changes they can induce within Aβ species remains undefined. Here, we describe highly resistant Aβ42 oligomers that are produced in cellular membrane compartments. They are formed in cells by processing of the APP amyloidogenic C-terminal fragment (C99), or by direct expression of a peptide corresponding to Aβ42, but not to Aβ40. By a point-mutation approach, we demonstrate that glycine-to-leucine mutations in the G
29 XXXG33 and G38 XXXA42 motifs dramatically affect the Aβ oligomerization process. G33 and G38 in these motifs are specifically involved in Aβ oligomerization; the G33L mutation strongly promotes oligomerization, while G38L blocks it with a dominant effect on G33 residue modification. Finally, we report that the secreted Aβ42 oligomers display pathological properties consistent with their suggested role in AD, but do not induce toxicity in survival assays with neuronal cells. Exposure of neurons to these Aβ42 oligomers dramatically affects neuronal differentiation and, consequently, neuronal network maturation. [ABSTRACT FROM AUTHOR]- Published
- 2016
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144. Needs in Nursing Homes and Their Relation with Cognitive and Functional Decline, Behavioral and Psychological Symptoms.
- Author
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Rita Ferreira, Ana, Camila Dias, Cláudia, Fernandes, Lia, Kandimalla, Ramesh, and Lorenzo-López, Laura
- Subjects
NURSING home care ,COGNITIVE ability ,BEHAVIOR disorders ,PATHOLOGICAL psychology ,MENTAL depression - Abstract
Unmet needs are becoming acknowledged as better predictors of the worst prognostic outcomes than common measures of functional or cognitive decline. Their accurate assessment is a pivotal component of effective care delivery, particularly in institutionalized care where little is known about the needs of its residents, many of whom suffer from dementia and show complex needs. The aims of this study were to describe the needs of an institutionalized sample and to analyze its relationship with demographic and clinical characteristics. A cross-sectional study was conducted with a sample from three nursing homes. All residents were assessed with a comprehensive protocol that included Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS-15), Neuropsychiatric Inventory (NPI) and Adults and Older Adults Functional Inventory (IAFAI). To identify needs, the Camberwell Assessment of Need for the Elderly (CANE) was used. The final sample included 175 residents with a mean age of 81 standard deviation (SD = 10) years. From these, 58.7% presented cognitive deficit (MMSE) and 45.2% depressive symptoms (GDS). Statistically significant negative correlations were found between MMSE score and met (r
s = -0.425), unmet (rs = -0.369) and global needs (rs = -0.565). Data also showed significant correlations between depressive symptoms and unmet (rs = 0.683) and global needs (rs = 0.407), and between behavioral and psychological symptoms (BPSD) and unmet (rs = 0.181) and global needs (rs = 0.254). Finally, significant correlations between functional impairment and met (rs = 0.642), unmet (rs = 0.505) and global needs (rs = 0.796) were also found. These results suggest that in this sample, more unmet needs are associated with the worst outcomes measured. This is consistent with previous findings and seems to demonstrate that the needs of those institutionalized elderly remain under-diagnosed and untreated. [ABSTRACT FROM AUTHOR]- Published
- 2016
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145. The Differentiation of Amnestic Type MCI from the Non-Amnestic Types by Structural MRI.
- Author
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Csukly, Gábor, Sirály, Enikö, Fodor, Zsuzsanna, Horváth, András, Salacz, Pál, Hidasi, Zoltán, Csibri, Éva, Rudas, Gábor, Szabó, Ádám, Rogers, Baxter P., and Kandimalla, Ramesh
- Subjects
AMNESTIC mild cognitive impairment ,MILD cognitive impairment ,MAGNETIC resonance imaging of the brain ,SIZE of brain ,MEMORY research ,EFFECT sizes (Statistics) - Abstract
Introduction: While amnestic mild cognitive impairment (aMCI) and non-amnestic mild cognitive impairment (naMCI) are theoretically different entities, only a few investigations studied the structural brain differences between these subtypes of mild cognitive impairment. The aim of the study was to find the structural differences between aMCI and naMCI, and to replicate previous findings on the differentiation between aMCI and healthy controls. Methods: Altogether 62 aMCI, naMCI, and healthy control subjects were included into the study based on the Petersen criteria. All patients underwent a routine brain MR examination, and a detailed neuropsychological examination. Results: The sizes of the hippocampus, the entorhinal cortex and the amygdala were decreased in aMCI relative to naMCI and to controls. Furthermore the cortical thickness of the entorhinal cortex, the fusiform gyrus, the precuneus and the isthmus of the cingulate gyrus were significantly decreased in aMCI relative to naMCI and healthy controls. The largest differences relative to controls were detected for the volume of the hippocampus (18% decrease vs. controls) and the cortical thickness (20% decrease vs. controls) of the entorhinal cortex: 1.6 and 1.4 in terms of Cohen's d. Only the volume of the precuneus were decreased in the naMCI group (5% decrease) compared to the control subjects: 0.9 in terms of Cohen's d. Significant between group differences were also found in the neuropsychological test results: a decreased anterograde, retrograde memory, and category fluency performance was detected in the aMCI group relative to controls and naMCI subjects. Subjects with naMCI showed decreased letter fluency relative to controls, while both MCI groups showed decreased executive functioning relative to controls as measured by the Trail Making test part B. Memory performance in the aMCI group and in the entire sample correlated with the thickness of the entorhinal cortex and with the volume of the amygdala. Conclusion: The amnestic mild cognitive impairment/non-amnestic mild cognitive impairment separation is not only theoretical but backed by structural imaging methods and neuropsychological tests. A better knowledge of the MCI subtypes can help to predict the direction of progression and create targeted prevention. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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146. Frequency-Dependent Brain Regional Homogeneity Alterations in Patients with Mild Cognitive Impairment during Working Memory State Relative to Resting State.
- Author
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Pengyun Wang, Rui Li, Jing Yu, Zirui Huang, Juan Li, Matthäus, Franziska, and Kandimalla, Ramesh
- Subjects
BRAIN abnormalities ,MILD cognitive impairment ,SHORT-term memory ,PREFRONTAL cortex ,CEREBELLUM - Abstract
Several studies have reported working memory deficits in patients with mild cognitive impairment (MCI). However, previous studies investigating the neural mechanisms of MCI have primarily focused on brain activity alterations during working memory tasks. No study to date has compared brain network alterations in the working memory state between MCI patients and normal control (NC) subjects. Therefore, using the index of regional homogeneity (ReHo), we explored brain network impairments in MCI patients during a working memory task relative to the resting state, and identified frequency-dependent effects in separate frequency bands. Our results indicate that, in MCI patients, ReHo is altered in the posterior cingulate cortex (PCC) in the slow-3 band (0.073-0.198 Hz), and in the bottom of the right occipital lobe and part of the right cerebellum, the right thalamus, a diffusing region in the bilateral prefrontal cortex (PFC), the left and right parietal-occipital regions, and the right angular gyrus in the slow-5 band (0.01-0.027 Hz). Furthermore, in NCs, the value of ReHo in clusters belonging to the default mode network (DMN) decreased, while the value of ReHo in clusters belonging to the attentional network increased during the task state. However, this pattern was reversed in MCI patients, and was associated with decreased working memory performance. In addition, we identified altered functional connectivity of the abovementioned regions with other parts of the brain in MCI patients. This is the first study to compare frequency-dependent alterations of ReHo in MCI patients between resting and working memory states. The results provide a new perspective regarding the neural mechanisms of working memory deficits in MCI patients, and extend our knowledge of altered brain patterns in resting and task-evoked states. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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147. Dynamic Progression of White Matter Hyperintensities in Alzheimer's Disease and Normal Aging: Results from the Sunnybrook Dementia Study.
- Author
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Ramirez, Joel, McNeely, Alicia A., Berezuk, Courtney, Gao, Fuqiang, Black, Sandra E., Popescu, Bogdan O., and Kandimalla, Ramesh
- Subjects
ALZHEIMER'S disease ,AGING ,DEMENTIA research ,BRAIN diseases ,MAGNETIC resonance imaging ,DISEASE progression - Abstract
Although white matter hyperintensities (WMH), markers of cerebral small vessel disease (SVD), are believed to generally increase over time, some studies have shown sharp decreases after therapeutic intervention, suggesting that WMH progression may be more dynamic than previously thought. Our primary goal was to examine dynamic progression of WMH in a real-world sample of Alzheimer's disease (AD) patients and normal elderly (NC), with varying degrees of SVD. WMH volumes from serial magnetic resonance imaging (MRI; mean = 1.8 years) were measured from NC (n = 44) and AD patients (n = 113) with high and low SVD burden. Dynamic progression for each individual was measured using spatial overlap images to assess shrinkage, growth, and stable WMH volumes. Significant group differences were found for shrinkage (p < 0.001), growth (p < 0.001) and stable (p < 0.001) WMH, where the AD high SVD group showed the largest changes relative to low SVD and NC. Our results suggest spatial progression measured at the individual patient level may be more sensitive to the dynamic nature of WMH. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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148. Differences in F-Wave Characteristics between Spinobulbar Muscular Atrophy and Amyotrophic Lateral Sclerosis.
- Author
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Jia Fang, Liying Cui, Mingsheng Liu, Yuzhou Guan, Xiaoguang Li, Dawei Li, Bo Cui, Dongchao Shen, Qingyun Ding, Hiroshi Morita, and Kandimalla, Ramesh
- Subjects
MUSCULAR atrophy ,MOTOR neuron diseases ,AMYOTROPHIC lateral sclerosis ,NEURAL conduction ,AMPLITUDE modulation detectors - Abstract
There is limited data on the differences in F-wave characteristics between spinobulbar muscular atrophy (SBMA) and lower motor neuron dominant (LMND) amyotrophic lateral sclerosis (ALS). We compared the parameters of F-waves recorded bilaterally from the median, ulnar, tibial, and deep peroneal nerves in 32 SBMA patients, 37 patients with LMND ALS, and 30 normal controls. The maximum F-wave amplitudes, frequencies of giant F-waves, and frequencies of patients with giant F-waves in all nerves examined were significantly higher in the SBMA patients than in the ALS patients and the normal controls. The mean F-wave amplitude, maximum F-wave amplitude, frequency of giant F-waves, and frequency of patients with giant F-waves in the median and deep peroneal nerves were comparable between the ALS patients and normal controls. Giant F-waves were detected in multiple nerves and were often symmetrical in the SBMA patients compared with the ALS patients. The number of nerves with giant F-waves seems to be the most robust variable for differentiation of SBMA from ALS, with an area under the curve of 0.908 (95% CI: 0.835-0.982). A cut-off value of the number of nerves with giant F-waves (≥3) for diagnosing SBMA showed high sensitivity and specificity: 85% sensitivity and 81% specificity vs. ALS patients. No significant correlations were found between the pooled frequency of giant F-waves and disease duration in the SBMA (r = 0.162, P = 0.418) or ALS groups (r = 0.107, P = 0.529). Our findings suggested that F-waves might be used to discriminate SBMA from ALS, even at early stages of disease. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
149. Cross-View Neuroimage Pattern Analysis in Alzheimer's Disease Staging.
- Author
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Sidong Liu, Weidong Cai, Sonia Pujo, Ron Kikinis, Feng, Dagan D., D'Souza, Maria Mathew, and Kandimalla, Ramesh
- Subjects
BRAIN imaging ,PATTERN recognition systems ,ALZHEIMER'S disease diagnosis ,DISEASE progression ,DEMENTIA prevention - Abstract
The research on staging of pre-symptomatic and prodromal phase of neurological disorders, e.g., Alzheimer's disease (AD), is essential for prevention of dementia. New strategies for AD staging with a focus on early detection, are demanded to optimize potential efficacy of disease-modifying therapies that can halt or slow the disease progression. Recently, neuroimaging are increasingly used as additional research-based markers to detect AD onset and predict conversion of MCI and normal control (NC) to AD. Researchers have proposed a variety of neuroimaging biomarkers to characterize the patterns of the pathology of AD and MCI, and suggested that multi-view neuroimaging biomarkers could lead to better performance than single-view biomarkers in AD staging. However, it is still unclear what leads to such synergy and how to preserve or maximize. In an attempt to answer these questions, we proposed a cross-view pattern analysis framework for investigating the synergy between different neuroimaging biomarkers. We quantitatively analyzed nine types of biomarkers derived from FDG-PET and T1-MRI, and evaluated their performance in a task of classifying AD, MCI, and NC subjects obtained from the ADNI baseline cohort. The experiment results showed that these biomarkers could depict the pathology of AD from different perspectives, and output distinct patterns that are significantly associated with the disease progression. Most importantly, we found that these features could be separated into clusters, each depicting a particular aspect; and the inter-cluster features could always achieve better performance than the intra-cluster features in AD staging. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
150. Magnetic Resonance Q Mapping Reveals a Decrease in Microvessel Density in the arcAβ Mouse Model of Cerebral Amyloidosis.
- Author
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Ielacqua, Giovanna D., Schlegel, Felix, Füchtemeier, Martina, Xandry, Jael, Rudin, Markus, Klohs, Jan, Charriaut-Marlangue, Christiane, and Kandimalla, Ramesh
- Subjects
AMYLOIDOSIS diagnosis ,BRAIN mapping ,MAGNETIC resonance imaging of the brain ,CEREBROVASCULAR disease diagnosis ,LABORATORY mice ,ALZHEIMER'S patients - Abstract
Alterations in density and morphology of the cerebral microvasculature have been reported to occur in Alzheimer's disease patients and animal models of the disease. In this study we compared magnetic resonance imaging (MRI) techniques for their utility to detect age-dependent changes of the cerebral vasculature in the arcAβ mouse model of cerebral amyloidosis. Dynamic susceptibility contrast (DSC)-MRI was performed by tracking the passage of a superparamagnetic iron oxide nanoparticle in the brain with dynamic gradient echo planar imaging (EPI). From this measurements relative cerebral blood volume [rCBV(DSC)] and relative cerebral blood flow (rCBF) were estimated. For the same animal maps of the relaxation shift index Q were computed from high resolution gradient echo and spin echo data that were acquired before and after superparamagnetic iron oxide (SPIO) nanoparticle injection. Q-values were used to derive estimates of microvessel density. The change in the relaxation rates ΔR
2 * obtained from pre- and post-contrast gradient echo data was used for the alternative determination of rCBV [rCBV(ΔR2 *)]. Linear mixed effects modeling found no significant association between rCBV(DSC), rCBV(ΔR2 *), rCBF, and Q with genotype in 13-month old mice [compared to age-matched non-transgenic littermates (NTLs)] for any of the evaluated brain regions. In 24-month old mice there was a significant association for rCBV(DSC) with genotype in the cerebral cortex, and for rCBV(ΔR2 *) in the cerebral cortex and cerebellum. For rCBF there was a significant association in the cerebellum but not in other brain regions. Q-values in the olfactory bulb, cerebral cortex, striatum, hippocampus, and cerebellum in 24-month old mice were significantly associated with genotype. In those regions Q-values were reduced between 11 and 26% in arcAβ mice compared to age-matched NTLs. Vessel staining with CD31 immunohistochemistry confirmed a reduction of microvessel density in the old arcAβ mice. We further demonstrated a region-specific association between parenchymal and vascular deposition of β-amyloid and decreased vascular density, without a correlation with the amount of Aβ deposition. We found that Q mapping was more suitable than the hemodynamic read-outs to detect amyloid-related degeneration of the cerebral microvasculature. [ABSTRACT FROM AUTHOR]- Published
- 2016
- Full Text
- View/download PDF
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