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Vigorous, regular physical exercise may slow disease progression in Alzheimer's disease

Devanand, Davangere P; Masurkar, Arjun V; Wisniewski, Thomas
ISSN: 1552-5279
CID: 5407172

Intracranial artery stenosis is associated with cortical thinning in stroke-free individuals of two longitudinal cohorts

Yang, Dixon; Masurkar, Arjun V; Khasiyev, Farid; Rundek, Tatjana; Wright, Clinton B; Elkind, Mitchell SV; Sacco, Ralph L; Gutierrez, Jose
ISSN: 1878-5883
CID: 5387992

Clinical Implications of Internal Carotid Arterial Tortuosity in Patients with White Matter Hyperintensities

Sun, Zhe; Li, Chenyang; Muccio, Marco; Masurkar, Arjun V.; Wisniewski, Thomas; Ge, Yulin
Background: White matter hyperintensities (WMHs) are observed frequently on MRI in elderly and associated with cognitive dysfunction. Many studies focused on intracranial small vessel disease (SVD), however, few studies linked WMHs with changes of extracranial large feeding arteries. We aimed to investigate the effects of internal carotid artery (ICA) tortuosity changes through quantitative MR Angiography. Method: Fifty-seven patients (age: 72.98±5.62; 32 females/25 males) with WMHs were included. WMHs lesions were semi-automatically segmented on FLAIR images. ICAs were segmented on the TOF images to generate tortuosity quantitative metrics, including tortuosity index (TI), inflection count metric (ICM), and ICA angle (Figure 1). According to the Fazekas scores, patients were categorized into mild, moderate and severe groups as summarized in Table 1. One-way ANOVA analyses were applied to reveal the difference of averaged bilateral ICAs' tortuosity measurements. Pearson's correlation coefficients were calculated to quantitatively investigate the relationship between tortuosity and volumes of lesions that are apart from the ventricle in subcortical white matter, i.e., deep white matter lesions (DWMLs), as well as the lesions attached with the ventricular system, i.e., periventricular white matter lesions (PVWMLs). Result: Patients with higher Fazekas scores have higher TI and ICM, indicating higher tortuosity (Figure 2). The correlation results showed that TI and ICM were positively correlated with DWMLs volumes (r = 0.33, P< 0.05; r = 0.4, P< 0.01), however, they did not show associations with PVWMLs. While there's no correlation between averaged bilateral ICA angles and DWMLs or PVWMLs, we found significant correlations between left ICA angles and DWML volumes on left brain (r =0.56, P < 0.005) as well as between right ICA angles and DWML volumes on right brain (r = 0.49, P < 0.05) (Figure 3). Conclusion: Tortuosity measurements derived from TOF images showed that subjects with higher degree of ICA tortuosity had higher lesion volumes of DWMLs not PVWMLs, indicating DWMLs may have different etiologies such as ischemic origin. The findings also highlight the importance of ICA angle as a risk factor for WMHs development which might be associated with the local hemodynamic shear stress at the bulb, where the ICA plaques are often developed.
ISSN: 1552-5260
CID: 5393902

Cortical Myelin Profile Variations in Healthy Aging Brain: A T1w/T2w Ratio Study

Sui, Yu-Veronica; Masurkar, Arjun V; Rusinek, Henry; Reisberg, Barry; Lazar, Mariana
Demyelination is observed in both healthy aging and age-related neurodegenerative disorders. While the significance of myelin within the cortex is well acknowledged, studies focused on intracortical demyelination and depth-specific structural alterations in normal aging are lacking. Using the recently available Human Connectome Project Aging dataset, we investigated intracortical myelin in a normal aging population using the T1w/T2w ratio. To capture the fine changes across cortical depths, we employed a surface-based approach by constructing cortical profiles traveling perpendicularly through the cortical ribbon and sampling T1w/T2w values. The curvatures of T1w/T2w cortical profiles may be influenced by differences in local myeloarchitecture and other tissue properties, which are known to vary across cortical regions. To quantify the shape of these profiles, we parametrized the level of curvature using a nonlinearity index (NLI) that measures the deviation of the profile from a straight line. We showed that NLI exhibited a steep decline in aging that was independent of local cortical thinning. Further examination of the profiles revealed that lower T1w/T2w near the gray-white matter boundary and superficial cortical depths were major contributors to the apparent NLI variations with age. These findings suggest that demyelination and changes in other T1w/T2w related tissue properties in normal aging may be depth-specific and highlight the potential of NLI as a unique marker of microstructural alterations within the cerebral cortex.
PMID: 36368498
ISSN: 1095-9572
CID: 5357642

Generalizable deep learning model for early Alzheimer's disease detection from structural MRIs

Liu, Sheng; Masurkar, Arjun V; Rusinek, Henry; Chen, Jingyun; Zhang, Ben; Zhu, Weicheng; Fernandez-Granda, Carlos; Razavian, Narges
Early diagnosis of Alzheimer's disease plays a pivotal role in patient care and clinical trials. In this study, we have developed a new approach based on 3D deep convolutional neural networks to accurately differentiate mild Alzheimer's disease dementia from mild cognitive impairment and cognitively normal individuals using structural MRIs. For comparison, we have built a reference model based on the volumes and thickness of previously reported brain regions that are known to be implicated in disease progression. We validate both models on an internal held-out cohort from The Alzheimer's Disease Neuroimaging Initiative (ADNI) and on an external independent cohort from The National Alzheimer's Coordinating Center (NACC). The deep-learning model is accurate, achieved an area-under-the-curve (AUC) of 85.12 when distinguishing between cognitive normal subjects and subjects with either MCI or mild Alzheimer's dementia. In the more challenging task of detecting MCI, it achieves an AUC of 62.45. It is also significantly faster than the volume/thickness model in which the volumes and thickness need to be extracted beforehand. The model can also be used to forecast progression: subjects with mild cognitive impairment misclassified as having mild Alzheimer's disease dementia by the model were faster to progress to dementia over time. An analysis of the features learned by the proposed model shows that it relies on a wide range of regions associated with Alzheimer's disease. These findings suggest that deep neural networks can automatically learn to identify imaging biomarkers that are predictive of Alzheimer's disease, and leverage them to achieve accurate early detection of the disease.
PMID: 36253382
ISSN: 2045-2322
CID: 5352422

Obstructive Sleep Apnea and Hypertension with Longitudinal β-Amyloid Burden and Cognitive Changes

Bubu, Omonigho M; Kaur, Sonya S; Mbah, Alfred K; Umasabor-Bubu, Ogie Q; Ramos-Cejudo, Jaime; Debure, Ludovic; Mullins, Anna E; Parekh, Ankit; Kam, Korey; Osakwe, Zainab T; Williams, Ellita T; Turner, Arlener D; Glodzik, Lidia; Rapoport, David M; Ogedegbe, Gbenga; Fieremans, Els; de Leon, Mony J; Ayappa, Indu; Jean-Louis, Girardin; Masurkar, Arjun V; Varga, Andrew W; Osorio, Ricardo S
PMID: 35550019
ISSN: 1535-4970
CID: 5213082

Comparison of serum neurodegenerative biomarkers among hospitalized COVID-19 patients versus non-COVID subjects with normal cognition, mild cognitive impairment, or Alzheimer's dementia

Frontera, Jennifer A; Boutajangout, Allal; Masurkar, Arjun V; Betensky, Rebecca A; Ge, Yulin; Vedvyas, Alok; Debure, Ludovic; Moreira, Andre; Lewis, Ariane; Huang, Joshua; Thawani, Sujata; Balcer, Laura; Galetta, Steven; Wisniewski, Thomas
INTRODUCTION/BACKGROUND:Neurological complications among hospitalized COVID-19 patients may be associated with elevated neurodegenerative biomarkers. METHODS:Among hospitalized COVID-19 patients without a history of dementia (N = 251), we compared serum total tau (t-tau), phosphorylated tau-181 (p-tau181), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCHL1), and amyloid beta (Aβ40,42) between patients with or without encephalopathy, in-hospital death versus survival, and discharge home versus other dispositions. COVID-19 patient biomarker levels were also compared to non-COVID cognitively normal, mild cognitive impairment (MCI), and Alzheimer's disease (AD) dementia controls (N = 161). RESULTS:Admission t-tau, p-tau181, GFAP, and NfL were significantly elevated in patients with encephalopathy and in those who died in-hospital, while t-tau, GFAP, and NfL were significantly lower in those discharged home. These markers correlated with severity of COVID illness. NfL, GFAP, and UCHL1 were higher in COVID patients than in non-COVID controls with MCI or AD. DISCUSSION/CONCLUSIONS:Neurodegenerative biomarkers were elevated to levels observed in AD dementia and associated with encephalopathy and worse outcomes among hospitalized COVID-19 patients.
PMID: 35023610
ISSN: 1552-5279
CID: 5116752

New insights into the genetic etiology of Alzheimer's disease and related dementias

Bellenguez, Céline; Küçükali, Fahri; Jansen, Iris E; Kleineidam, Luca; Moreno-Grau, Sonia; Amin, Najaf; Naj, Adam C; Campos-Martin, Rafael; Grenier-Boley, Benjamin; Andrade, Victor; Holmans, Peter A; Boland, Anne; Damotte, Vincent; van der Lee, Sven J; Costa, Marcos R; Kuulasmaa, Teemu; Yang, Qiong; de Rojas, Itziar; Bis, Joshua C; Yaqub, Amber; Prokic, Ivana; Chapuis, Julien; Ahmad, Shahzad; Giedraitis, Vilmantas; Aarsland, Dag; Garcia-Gonzalez, Pablo; Abdelnour, Carla; Alarcón-Martín, Emilio; Alcolea, Daniel; Alegret, Montserrat; Alvarez, Ignacio; Álvarez, Victoria; Armstrong, Nicola J; Tsolaki, Anthoula; Antúnez, Carmen; Appollonio, Ildebrando; Arcaro, Marina; Archetti, Silvana; Pastor, Alfonso Arias; Arosio, Beatrice; Athanasiu, Lavinia; Bailly, Henri; Banaj, Nerisa; Baquero, Miquel; Barral, Sandra; Beiser, Alexa; Pastor, Ana Belén; Below, Jennifer E; Benchek, Penelope; Benussi, Luisa; Berr, Claudine; Besse, Céline; Bessi, Valentina; Binetti, Giuliano; Bizarro, Alessandra; Blesa, Rafael; Boada, Mercè; Boerwinkle, Eric; Borroni, Barbara; Boschi, Silvia; Bossù, Paola; BrÃ¥then, Geir; Bressler, Jan; Bresner, Catherine; Brodaty, Henry; Brookes, Keeley J; Brusco, Luis Ignacio; Buiza-Rueda, Dolores; Bûrger, Katharina; Burholt, Vanessa; Bush, William S; Calero, Miguel; Cantwell, Laura B; Chene, Geneviève; Chung, Jaeyoon; Cuccaro, Michael L; Carracedo, Ángel; Cecchetti, Roberta; Cervera-Carles, Laura; Charbonnier, Camille; Chen, Hung-Hsin; Chillotti, Caterina; Ciccone, Simona; Claassen, Jurgen A H R; Clark, Christopher; Conti, Elisa; Corma-Gómez, Anaïs; Costantini, Emanuele; Custodero, Carlo; Daian, Delphine; Dalmasso, Maria Carolina; Daniele, Antonio; Dardiotis, Efthimios; Dartigues, Jean-François; de Deyn, Peter Paul; de Paiva Lopes, Katia; de Witte, Lot D; Debette, Stéphanie; Deckert, Jürgen; Del Ser, Teodoro; Denning, Nicola; DeStefano, Anita; Dichgans, Martin; Diehl-Schmid, Janine; Diez-Fairen, Mónica; Rossi, Paolo Dionigi; Djurovic, Srdjan; Duron, Emmanuelle; Düzel, Emrah; Dufouil, Carole; Eiriksdottir, Gudny; Engelborghs, Sebastiaan; Escott-Price, Valentina; Espinosa, Ana; Ewers, Michael; Faber, Kelley M; Fabrizio, Tagliavini; Nielsen, Sune Fallgaard; Fardo, David W; Farotti, Lucia; Fenoglio, Chiara; Fernández-Fuertes, Marta; Ferrari, Raffaele; Ferreira, Catarina B; Ferri, Evelyn; Fin, Bertrand; Fischer, Peter; Fladby, Tormod; Fließbach, Klaus; Fongang, Bernard; Fornage, Myriam; Fortea, Juan; Foroud, Tatiana M; Fostinelli, Silvia; Fox, Nick C; Franco-Macías, Emlio; Bullido, María J; Frank-García, Ana; Froelich, Lutz; Fulton-Howard, Brian; Galimberti, Daniela; García-Alberca, Jose Maria; García-González, Pablo; Garcia-Madrona, Sebastian; Garcia-Ribas, Guillermo; Ghidoni, Roberta; Giegling, Ina; Giorgio, Giaccone; Goate, Alison M; Goldhardt, Oliver; Gomez-Fonseca, Duber; González-Pérez, Antonio; Graff, Caroline; Grande, Giulia; Green, Emma; Grimmer, Timo; Grünblatt, Edna; Grunin, Michelle; Gudnason, Vilmundur; Guetta-Baranes, Tamar; Haapasalo, Annakaisa; Hadjigeorgiou, Georgios; Haines, Jonathan L; Hamilton-Nelson, Kara L; Hampel, Harald; Hanon, Olivier; Hardy, John; Hartmann, Annette M; Hausner, Lucrezia; Harwood, Janet; Heilmann-Heimbach, Stefanie; Helisalmi, Seppo; Heneka, Michael T; Hernández, Isabel; Herrmann, Martin J; Hoffmann, Per; Holmes, Clive; Holstege, Henne; Vilas, Raquel Huerto; Hulsman, Marc; Humphrey, Jack; Biessels, Geert Jan; Jian, Xueqiu; Johansson, Charlotte; Jun, Gyungah R; Kastumata, Yuriko; Kauwe, John; Kehoe, Patrick G; Kilander, Lena; StÃ¥hlbom, Anne Kinhult; Kivipelto, Miia; Koivisto, Anne; Kornhuber, Johannes; Kosmidis, Mary H; Kukull, Walter A; Kuksa, Pavel P; Kunkle, Brian W; Kuzma, Amanda B; Lage, Carmen; Laukka, Erika J; Launer, Lenore; Lauria, Alessandra; Lee, Chien-Yueh; Lehtisalo, Jenni; Lerch, Ondrej; Lleó, Alberto; Longstreth, William; Lopez, Oscar; de Munain, Adolfo Lopez; Love, Seth; Löwemark, Malin; Luckcuck, Lauren; Lunetta, Kathryn L; Ma, Yiyi; Macías, Juan; MacLeod, Catherine A; Maier, Wolfgang; Mangialasche, Francesca; Spallazzi, Marco; Marquié, Marta; Marshall, Rachel; Martin, Eden R; Montes, Angel Martín; Rodríguez, Carmen Martínez; Masullo, Carlo; Mayeux, Richard; Mead, Simon; Mecocci, Patrizia; Medina, Miguel; Meggy, Alun; Mehrabian, Shima; Mendoza, Silvia; Menéndez-González, Manuel; Mir, Pablo; Moebus, Susanne; Mol, Merel; Molina-Porcel, Laura; Montrreal, Laura; Morelli, Laura; Moreno, Fermin; Morgan, Kevin; Mosley, Thomas; Nöthen, Markus M; Muchnik, Carolina; Mukherjee, Shubhabrata; Nacmias, Benedetta; Ngandu, Tiia; Nicolas, Gael; Nordestgaard, Børge G; Olaso, Robert; Orellana, Adelina; Orsini, Michela; Ortega, Gemma; Padovani, Alessandro; Paolo, Caffarra; Papenberg, Goran; Parnetti, Lucilla; Pasquier, Florence; Pastor, Pau; Peloso, Gina; Pérez-Cordón, Alba; Pérez-Tur, Jordi; Pericard, Pierre; Peters, Oliver; Pijnenburg, Yolande A L; Pineda, Juan A; Piñol-Ripoll, Gerard; Pisanu, Claudia; Polak, Thomas; Popp, Julius; Posthuma, Danielle; Priller, Josef; Puerta, Raquel; Quenez, Olivier; Quintela, Inés; Thomassen, Jesper Qvist; Rábano, Alberto; Rainero, Innocenzo; Rajabli, Farid; Ramakers, Inez; Real, Luis M; Reinders, Marcel J T; Reitz, Christiane; Reyes-Dumeyer, Dolly; Ridge, Perry; Riedel-Heller, Steffi; Riederer, Peter; Roberto, Natalia; Rodriguez-Rodriguez, Eloy; Rongve, Arvid; Allende, Irene Rosas; Rosende-Roca, Maitée; Royo, Jose Luis; Rubino, Elisa; Rujescu, Dan; Sáez, María Eugenia; Sakka, Paraskevi; Saltvedt, Ingvild; Sanabria, Ángela; Sánchez-Arjona, María Bernal; Sanchez-Garcia, Florentino; Juan, Pascual Sánchez; Sánchez-Valle, Raquel; Sando, Sigrid B; Sarnowski, Chloé; Satizabal, Claudia L; Scamosci, Michela; Scarmeas, Nikolaos; Scarpini, Elio; Scheltens, Philip; Scherbaum, Norbert; Scherer, Martin; Schmid, Matthias; Schneider, Anja; Schott, Jonathan M; Selbæk, Geir; Seripa, Davide; Serrano, Manuel; Sha, Jin; Shadrin, Alexey A; Skrobot, Olivia; Slifer, Susan; Snijders, Gijsje J L; Soininen, Hilkka; Solfrizzi, Vincenzo; Solomon, Alina; Song, Yeunjoo; Sorbi, Sandro; Sotolongo-Grau, Oscar; Spalletta, Gianfranco; Spottke, Annika; Squassina, Alessio; Stordal, Eystein; Tartan, Juan Pablo; Tárraga, Lluís; Tesí, Niccolo; Thalamuthu, Anbupalam; Thomas, Tegos; Tosto, Giuseppe; Traykov, Latchezar; Tremolizzo, Lucio; Tybjærg-Hansen, Anne; Uitterlinden, Andre; Ullgren, Abbe; Ulstein, Ingun; Valero, Sergi; Valladares, Otto; Broeckhoven, Christine Van; Vance, Jeffery; Vardarajan, Badri N; van der Lugt, Aad; Dongen, Jasper Van; van Rooij, Jeroen; van Swieten, John; Vandenberghe, Rik; Verhey, Frans; Vidal, Jean-Sébastien; Vogelgsang, Jonathan; Vyhnalek, Martin; Wagner, Michael; Wallon, David; Wang, Li-San; Wang, Ruiqi; Weinhold, Leonie; Wiltfang, Jens; Windle, Gill; Woods, Bob; Yannakoulia, Mary; Zare, Habil; Zhao, Yi; Zhang, Xiaoling; Zhu, Congcong; Zulaica, Miren; Farrer, Lindsay A; Psaty, Bruce M; Ghanbari, Mohsen; Raj, Towfique; Sachdev, Perminder; Mather, Karen; Jessen, Frank; Ikram, M Arfan; de Mendonça, Alexandre; Hort, Jakub; Tsolaki, Magda; Pericak-Vance, Margaret A; Amouyel, Philippe; Williams, Julie; Frikke-Schmidt, Ruth; Clarimon, Jordi; Deleuze, Jean-François; Rossi, Giacomina; Seshadri, Sudha; Andreassen, Ole A; Ingelsson, Martin; Hiltunen, Mikko; Sleegers, Kristel; Schellenberg, Gerard D; van Duijn, Cornelia M; Sims, Rebecca; van der Flier, Wiesje M; Ruiz, Agustín; Ramirez, Alfredo; Lambert, Jean-Charles; Laczo, Jan; Matoska, Vaclav; Serpente, Maria; Assogna, Francesca; Piras, Fabrizio; Piras, Federica; Ciullo, Valentina; Shofany, Jacob; Ferrarese, Carlo; Andreoni, Simona; Sala, Gessica; Zoia, Chiara Paola; Zompo, Maria Del; Benussi, Alberto; Bastiani, Patrizia; Takalo, Mari; Natunen, Teemu; Laatikainen, Tiina; Tuomilehto, Jaakko; Antikainen, Riitta; Strandberg, Timo; Lindström, Jaana; Peltonen, Markku; Abraham, Richard; Al-Chalabi, Ammar; Bass, Nicholas J; Brayne, Carol; Brown, Kristelle S; Collinge, John; Craig, David; Deloukas, Pangiotis; Fox, Nick; Gerrish, Amy; Gill, Michael; Gwilliam, Rhian; Harold, Denise; Hollingworth, Paul; Johnston, Jarret A; Jones, Lesley; Lawlor, Brian; Livingston, Gill; Lovestone, Simon; Lupton, Michelle; Lynch, Aoibhinn; Mann, David; McGuinness, Bernadette; McQuillin, Andrew; O'Donovan, Michael C; Owen, Michael J; Passmore, Peter; Powell, John F; Proitsi, Petra; Rossor, Martin; Shaw, Christopher E; Smith, A David; Gurling, Hugh; Todd, Stephen; Mummery, Catherine; Ryan, Nathalie; Lacidogna, Giordano; Adarmes-Gómez, Ad; Mauleón, Ana; Pancho, Ana; Gailhajenet, Anna; Lafuente, Asunción; Macias-García, D; Martín, Elvira; Pelejà, Esther; Carrillo, F; Merlín, Isabel Sastre; Garrote-Espina, L; Vargas, Liliana; Carrion-Claro, M; Marín, M; Labrador, Ma; Buendia, Mar; Alonso, María Dolores; Guitart, Marina; Moreno, Mariona; Ibarria, Marta; Periñán, Mt; Aguilera, Nuria; Gómez-Garre, P; Cañabate, Pilar; Escuela, R; Pineda-Sánchez, R; Vigo-Ortega, R; Jesús, S; Preckler, Silvia; Rodrigo-Herrero, Silvia; Diego, Susana; Vacca, Alessandro; Roveta, Fausto; Salvadori, Nicola; Chipi, Elena; Boecker, Henning; Laske, Christoph; Perneczky, Robert; Anastasiou, Costas; Janowitz, Daniel; Malik, Rainer; Anastasiou, Anna; Parveen, Kayenat; Lage, Carmen; López-García, Sara; Antonell, Anna; Mihova, Kalina Yonkova; Belezhanska, Diyana; Weber, Heike; Kochen, Silvia; Solis, Patricia; Medel, Nancy; Lisso, Julieta; Sevillano, Zulma; Politis, Daniel G; Cores, Valeria; Cuesta, Carolina; Ortiz, Cecilia; Bacha, Juan Ignacio; Rios, Mario; Saenz, Aldo; Abalos, Mariana Sanchez; Kohler, Eduardo; Palacio, Dana Lis; Etchepareborda, Ignacio; Kohler, Matias; Novack, Gisela; Prestia, Federico Ariel; Galeano, Pablo; Castaño, Eduardo M; Germani, Sandra; Toso, Carlos Reyes; Rojo, Matias; Ingino, Carlos; Mangone, Carlos; Rubinsztein, David C; Teipel, Stefan; Fievet, Nathalie; Deramerourt, Vincent; Forsell, Charlotte; Thonberg, HÃ¥kan; Bjerke, Maria; Roeck, Ellen De; Martínez-Larrad, María Teresa; Olivar, Natividad; Aguilera, Nuria; Cano, Amanda; Cañabate, Pilar; Macias, Juan; Maroñas, Olalla; Nuñez-Llaves, Raúl; Olivé, Clàudia; Pelejá, Ester; Adarmes-Gómez, Astrid D; Alonso, María Dolores; Amer-Ferrer, Guillermo; Antequera, Martirio; Burguera, Juan Andrés; Carrillo, Fátima; Carrión-Claro, Mario; Casajeros, María José; Martinez de Pancorbo, Marian; Escuela, Rocío; Garrote-Espina, Lorena; Gómez-Garre, Pilar; Hevilla, Saray; Jesús, Silvia; Espinosa, Miguel Angel Labrador; Legaz, Agustina; López-García, Sara; Macias-García, Daniel; Manzanares, Salvadora; Marín, Marta; Marín-Muñoz, Juan; Marín, Tamara; Martínez, Begoña; Martínez, Victoriana; Martínez-Lage Álvarez, Pablo; Iriarte, Maite Mendioroz; Periñán-Tocino, María Teresa; Pineda-Sánchez, Rocío; Real de Asúa, Diego; Rodrigo, Silvia; Sastre, Isabel; Vicente, Maria Pilar; Vigo-Ortega, Rosario; Vivancos, Liliana; Epelbaum, Jacques; Hannequin, Didier; Campion, Dominique; Deramecourt, Vincent; Tzourio, Christophe; Brice, Alexis; Dubois, Bruno; Williams, Amy; Thomas, Charlene; Davies, Chloe; Nash, William; Dowzell, Kimberley; Morales, Atahualpa Castillo; Bernardo-Harrington, Mateus; Turton, James; Lord, Jenny; Brown, Kristelle; Vardy, Emma; Fisher, Elizabeth; Warren, Jason D; Rossor, Martin; Ryan, Natalie S; Guerreiro, Rita; Uphill, James; Bass, Nick; Heun, Reinhard; Kölsch, Heike; Schürmann, Britta; Lacour, André; Herold, Christine; Johnston, Janet A; Passmore, Peter; Powell, John; Patel, Yogen; Hodges, Angela; Becker, Tim; Warden, Donald; Wilcock, Gordon; Clarke, Robert; Deloukas, Panagiotis; Ben-Shlomo, Yoav; Hooper, Nigel M; Pickering-Brown, Stuart; Sussams, Rebecca; Warner, Nick; Bayer, Anthony; Heuser, Isabella; Drichel, Dmitriy; Klopp, Norman; Mayhaus, Manuel; Riemenschneider, Matthias; Pinchler, Sabrina; Feulner, Thomas; Gu, Wei; van den Bussche, Hendrik; Hüll, Michael; Frölich, Lutz; Wichmann, H-Erich; Jöckel, Karl-Heinz; O'Donovan, Michael; Owen, Michael; Bahrami, Shahram; Bosnes, Ingunn; Selnes, Per; Bergh, Sverre; Palotie, Aarno; Daly, Mark; Jacob, Howard; Matakidou, Athena; Runz, Heiko; John, Sally; Plenge, Robert; McCarthy, Mark; Hunkapiller, Julie; Ehm, Meg; Waterworth, Dawn; Fox, Caroline; Malarstig, Anders; Klinger, Kathy; Call, Kathy; Behrens, Tim; Loerch, Patrick; Mäkelä, Tomi; Kaprio, Jaakko; Virolainen, Petri; Pulkki, Kari; Kilpi, Terhi; Perola, Markus; Partanen, Jukka; Pitkäranta, Anne; Kaarteenaho, Riitta; Vainio, Seppo; Turpeinen, Miia; Serpi, Raisa; Laitinen, Tarja; Mäkelä, Johanna; Kosma, Veli-Matti; Kujala, Urho; Tuovila, Outi; Hendolin, Minna; Pakkanen, Raimo; Waring, Jeff; Riley-Gillis, Bridget; Liu, Jimmy; Biswas, Shameek; Diogo, Dorothee; Marshall, Catherine; Hu, Xinli; Gossel, Matthias; Graham, Robert; Cummings, Beryl; Ripatti, Samuli; Schleutker, Johanna; Arvas, Mikko; Carpén, Olli; Hinttala, Reetta; Kettunen, Johannes; Mannermaa, Arto; Laukkanen, Jari; Julkunen, Valtteri; Remes, Anne; Kälviäinen, Reetta; Peltola, Jukka; Tienari, Pentti; Rinne, Juha; Ziemann, Adam; Waring, Jeffrey; Esmaeeli, Sahar; Smaoui, Nizar; Lehtonen, Anne; Eaton, Susan; Lahdenperä, Sanni; van Adelsberg, Janet; Michon, John; Kerchner, Geoff; Bowers, Natalie; Teng, Edmond; Eicher, John; Mehta, Vinay; Gormley, Padhraig; Linden, Kari; Whelan, Christopher; Xu, Fanli; Pulford, David; Färkkilä, Martti; Pikkarainen, Sampsa; Jussila, Airi; Blomster, Timo; Kiviniemi, Mikko; Voutilainen, Markku; Georgantas, Bob; Heap, Graham; Rahimov, Fedik; Usiskin, Keith; Lu, Tim; Oh, Danny; Kalpala, Kirsi; Miller, Melissa; McCarthy, Linda; Eklund, Kari; Palomäki, Antti; Isomäki, Pia; Pirilä, Laura; Kaipiainen-Seppänen, Oili; Huhtakangas, Johanna; Lertratanakul, Apinya; Hochfeld, Marla; Bing, Nan; Gordillo, Jorge Esparza; Mars, Nina; Pelkonen, Margit; Kauppi, Paula; Kankaanranta, Hannu; Harju, Terttu; Close, David; Greenberg, Steven; Chen, Hubert; Betts, Jo; Ghosh, Soumitra; Salomaa, Veikko; Niiranen, Teemu; Juonala, Markus; Metsärinne, Kaj; Kähönen, Mika; Junttila, Juhani; Laakso, Markku; Pihlajamäki, Jussi; Sinisalo, Juha; Taskinen, Marja-Riitta; Tuomi, Tiinamaija; Challis, Ben; Peterson, Andrew; Chu, Audrey; Parkkinen, Jaakko; Muslin, Anthony; Joensuu, Heikki; Meretoja, Tuomo; Aaltonen, Lauri; Mattson, Johanna; Auranen, Annika; Karihtala, Peeter; Kauppila, Saila; Auvinen, Päivi; Elenius, Klaus; Popovic, Relja; Schutzman, Jennifer; Loboda, Andrey; Chhibber, Aparna; Lehtonen, Heli; McDonough, Stefan; Crohns, Marika; Kulkarni, Diptee; Kaarniranta, Kai; Turunen, Joni A; Ollila, Terhi; Seitsonen, Sanna; Uusitalo, Hannu; Aaltonen, Vesa; Uusitalo-Järvinen, Hannele; Luodonpää, Marja; Hautala, Nina; Loomis, Stephanie; Strauss, Erich; Chen, Hao; Podgornaia, Anna; Hoffman, Joshua; Tasanen, Kaisa; Huilaja, Laura; Hannula-Jouppi, Katariina; Salmi, Teea; Peltonen, Sirkku; Koulu, Leena; Harvima, Ilkka; Wu, Ying; Choy, David; Pussinen, Pirkko; Salminen, Aino; Salo, Tuula; Rice, David; Nieminen, Pekka; Palotie, Ulla; Siponen, Maria; Suominen, Liisa; Mäntylä, Päivi; Gursoy, Ulvi; Anttonen, Vuokko; Sipilä, Kirsi; Davis, Justin Wade; Quarless, Danjuma; Petrovski, Slavé; Wigmore, Eleonor; Chen, Chia-Yen; Bronson, Paola; Tsai, Ellen; Huang, Yunfeng; Maranville, Joseph; Shaikho, Elmutaz; Mohammed, Elhaj; Wadhawan, Samir; Kvikstad, Erika; Caliskan, Minal; Chang, Diana; Bhangale, Tushar; Pendergrass, Sarah; Holzinger, Emily; Chen, Xing; Hedman, Ã…sa; King, Karen S; Wang, Clarence; Xu, Ethan; Auge, Franck; Chatelain, Clement; Rajpal, Deepak; Liu, Dongyu; Call, Katherine; Xia, Tai-He; Brauer, Matt; Kurki, Mitja; Karjalainen, Juha; Havulinna, Aki; Jalanko, Anu; Palta, Priit; Della Briotta Parolo, Pietro; Zhou, Wei; Lemmelä, Susanna; Rivas, Manuel; Harju, Jarmo; Lehisto, Arto; Ganna, Andrea; Llorens, Vincent; Laivuori, Hannele; Rüeger, Sina; Niemi, Mari E; Tukiainen, Taru; Reeve, Mary Pat; Heyne, Henrike; Palin, Kimmo; Garcia-Tabuenca, Javier; Siirtola, Harri; Kiiskinen, Tuomo; Lee, Jiwoo; Tsuo, Kristin; Elliott, Amanda; Kristiansson, Kati; Hyvärinen, Kati; Ritari, Jarmo; Koskinen, Miika; Pylkäs, Katri; Kalaoja, Marita; Karjalainen, Minna; Mantere, Tuomo; Kangasniemi, Eeva; Heikkinen, Sami; Laakkonen, Eija; Sipeky, Csilla; Heron, Samuel; Karlsson, Antti; Jambulingam, Dhanaprakash; Rathinakannan, Venkat Subramaniam; Kajanne, Risto; Aavikko, Mervi; Jiménez, Manuel González; Della Briotta Parola, Pietro; Lehistö, Arto; Kanai, Masahiro; Kaunisto, Mari; Kilpeläinen, Elina; Sipilä, Timo P; Brein, Georg; Awaisa, Ghazal; Shcherban, Anastasia; Donner, Kati; Loukola, Anu; Laiho, Päivi; Sistonen, Tuuli; Kaiharju, Essi; Laukkanen, Markku; Järvensivu, Elina; Lähteenmäki, Sini; Männikkö, Lotta; Wong, Regis; Mattsson, Hannele; Hiekkalinna, Tero; Paajanen, Teemu; Pärn, Kalle; Gracia-Tabuenca, Javier; Abner, Erin; Adams, Perrie M; Aguirre, Alyssa; Albert, Marilyn S; Albin, Roger L; Allen, Mariet; Alvarez, Lisa; Apostolova, Liana G; Arnold, Steven E; Asthana, Sanjay; Atwood, Craig S; Ayres, Gayle; Baldwin, Clinton T; Barber, Robert C; Barnes, Lisa L; Barral, Sandra; Beach, Thomas G; Becker, James T; Beecham, Gary W; Beekly, Duane; Below, Jennifer E; Benchek, Penelope; Benitez, Bruno A; Bennett, David; Bertelson, John; Margaret, Flanagan E; Bird, Thomas D; Blacker, Deborah; Boeve, Bradley F; Bowen, James D; Boxer, Adam; Brewer, James; Burke, James R; Burns, Jeffrey M; Bush, Will S; Buxbaum, Joseph D; Cairns, Nigel J; Cao, Chuanhai; Carlson, Christopher S; Carlsson, Cynthia M; Carney, Regina M; Carrasquillo, Minerva M; Chasse, Scott; Chesselet, Marie-Francoise; Chesi, Alessandra; Chin, Nathaniel A; Chui, Helena C; Chung, Jaeyoon; Craft, Suzanne; Crane, Paul K; Cribbs, David H; Crocco, Elizabeth A; Cruchaga, Carlos; Cuccaro, Michael L; Cullum, Munro; Darby, Eveleen; Davis, Barbara; De Jager, Philip L; DeCarli, Charles; DeToledo, John; Dick, Malcolm; Dickson, Dennis W; Dombroski, Beth A; Doody, Rachelle S; Duara, Ranjan; Ertekin-Taner, Nilüfer; Evans, Denis A; Fairchild, Thomas J; Fallon, Kenneth B; Farlow, Martin R; Farrell, John J; Fernandez-Hernandez, Victoria; Ferris, Steven; Frosch, Matthew P; Fulton-Howard, Brian; Galasko, Douglas R; Gamboa, Adriana; Gearing, Marla; Geschwind, Daniel H; Ghetti, Bernardino; Gilbert, John R; 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Wang, Yanbing; Weinstein, Galit; Williams, Dylan; Wittfeld, Katharina; Yanek, Lisa; Yang, Yunju
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
PMID: 35379992
ISSN: 1546-1718
CID: 5213092

Cognitive Function among World Trade Center-Exposed Community Members with Mental Health Symptoms

Rosen, Rebecca; Shao, Yongzhao; Zhang, Qiao; Bao, Jia; Zhang, Yian; Masurkar, Arjun; Wisniewski, Thomas; Urban, Nina; Reibman, Joan
The World Trade Center Environmental Health Center (WTC EHC), is a federally designated clinical center of excellence for surveillance and treatment of WTC disaster exposed community members (WTC Survivors). Cognitive impairment (CI) has been extensively described in WTC responders and a concern for progressive impairment in all WTC disaster exposed groups has been raised. Cognitive status, however, has not been systematically characterized in the WTC Survivor population. We describe cognitive status in a subgroup of the Survivor population referred for mental health evaluation (N = 480) in the WTC EHC as measured by scores on the Montreal Cognitive Assessment (MoCA) instrument, and examine their association with WTC exposures and individual-level covariates including PTSD and depression screening inventory scores. In regression analyses, probable cognitive impairment (MoCA score &lt; 26) was found in 59% of the study subjects and was significantly associated with age, race/ethnicity, education, income, depression and PTSD scores. Being caught in the dust cloud on 11 September 2011 was significantly associated with cognitive impairment even after controlling for the above. These data suggest an association with cognitive dysfunction in WTC Survivors with exposure to the toxic dust/fumes and psychological stress from the 9/11 terrorist attack and warrant further systematic study.
PMID: 35329128
ISSN: 1660-4601
CID: 5184832

Exploration of Rapid Automatized Naming and Standard Visual Tests in Prodromal Alzheimer Disease Detection

Wu, Shirley Z; Nolan-Kenney, Rachel; Moehringer, Nicholas J; Hasanaj, Lisena F; Joseph, Binu M; Clayton, Ashley M; Rucker, Janet C; Galetta, Steven L; Wisniewski, Thomas M; Masurkar, Arjun V; Balcer, Laura J
BACKGROUND:Visual tests in Alzheimer disease (AD) have been examined over the last several decades to identify a sensitive and noninvasive marker of the disease. Rapid automatized naming (RAN) tasks have shown promise for detecting prodromal AD or mild cognitive impairment (MCI). The purpose of this investigation was to determine the capacity for new rapid image and number naming tests and other measures of visual pathway structure and function to distinguish individuals with MCI due to AD from those with normal aging and cognition. The relation of these tests to vision-specific quality of life scores was also examined in this pilot study. METHODS:Participants with MCI due to AD and controls from well-characterized NYU research and clinical cohorts performed high and low-contrast letter acuity (LCLA) testing, as well as RAN using the Mobile Universal Lexicon Evaluation System (MULES) and Staggered Uneven Number test, and vision-specific quality of life scales, including the 25-Item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and 10-Item Neuro-Ophthalmic Supplement. Individuals also underwent optical coherence tomography scans to assess peripapillary retinal nerve fiber layer and ganglion cell/inner plexiform layer thicknesses. Hippocampal atrophy on brain MRI was also determined from the participants' Alzheimer disease research center or clinical data. RESULTS:Participants with MCI (n = 14) had worse binocular LCLA at 1.25% contrast compared with controls (P = 0.009) and longer (worse) MULES test times (P = 0.006) with more errors in naming images (P = 0.009) compared with controls (n = 16). These were the only significantly different visual tests between groups. MULES test times (area under the receiver operating characteristic curve [AUC] = 0.79), MULES errors (AUC = 0.78), and binocular 1.25% LCLA (AUC = 0.78) showed good diagnostic accuracy for distinguishing MCI from controls. A combination of the MULES score and 1.25% LCLA demonstrated the greatest capacity to distinguish (AUC = 0.87). These visual measures were better predictors of MCI vs control status than the presence of hippocampal atrophy on brain MRI in this cohort. A greater number of MULES test errors (rs = -0.50, P = 0.005) and worse 1.25% LCLA scores (rs = 0.39, P = 0.03) were associated with lower (worse) NEI-VFQ-25 scores. CONCLUSIONS:Rapid image naming (MULES) and LCLA are able to distinguish MCI due to AD from normal aging and reflect vision-specific quality of life. Larger studies will determine how these easily administered tests may identify patients at risk for AD and serve as measures in disease-modifying therapy clinical trials.
PMID: 34029274
ISSN: 1536-5166
CID: 4878882