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Background: Increasing research suggests that gait abnormalities can be a risk factor for Alzheimer's Disease (AD). Notably, there is growing evidence highlighting this risk factor in individuals with amnestic Mild Cognitive Impairment (aMCI), however further studies are needed. The aim of this study is to analyze cognitive tests results and brain-related measures over time in aMCI and examine how the presence of gait abnormalities (neurological or orthopedic) or normal gait affects these trends. Additionally, we sought to assess the significance of gait and gait-related measures as prognostic indicators for the progression from aMCI to AD dementia, comparing those who converted to AD with those who remained with a stable aMCI diagnosis during the follow-up. Methods: Four hundred two individuals with aMCI from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were included. Robust linear mixed-effects models were used to study the impact of gait abnormalities on a comprehensive neuropsychological battery over 36 months while controlling for relevant medical variables at baseline. The impact of gait on brain measures was also investigated. Lastly, the Cox proportional-hazards model was used to explore the prognostic relevance of abnormal gait and neuropsychological associated tests. Results: While controlling for relevant covariates, we found that gait abnormalities led to a greater decline over time in attention (DSST) and global cognition (MMSE). Intriguingly, psychomotor speed (TMT-A) and divided attention (TMT-B) declined uniquely in the abnormal gait group. Conversely, specific AD global cognition tests (ADAS-13) and auditory-verbal memory (RAVLT immediate recall) declined over time independently of gait profile. All the other cognitive tests were not significantly affected by time or by gait profile. In addition, we found that ventricles size increased faster in the abnormal gait group compared to the normal gait group. In terms of prognosis, abnormal gait (HR = 1.7), MMSE (HR = 1.09), and DSST (HR = 1.03) covariates showed a higher impact on AD dementia conversion. Conclusions: The importance of the link between gait and related cognitive functions in terms of diagnosis, prognosis, and rehabilitation in aMCI is critical. We showed that in aMCI gait abnormalities lead to executive functions/attention deterioration and conversion to AD dementia.
Prognostic relevance of gait-related cognitive functions for dementia conversion in amnestic mild cognitive impairment
Tuena, Cosimo;Maestri, Sara;Serino, Silvia;Pedroli, Elisa;Stramba-Badiale, Marco;Riva, Giuseppe;Silbert, Lisa C.;Lind, Betty;Crissey, Rachel;Kaye, Jeffrey A.;Carter, Raina;Dolen, Sara;Quinn, Joseph;Schneider, Lon S.;Pawluczyk, Sonia;Becerra, Mauricio;Teodoro, Liberty;Dagerman, Karen;Spann, Bryan M.;Brewer, James;Fleisher, Adam;Vanderswag, Helen;Ziolkowski, Jaimie;Heidebrink, Judith L.;Zbizek-Nulph, Lisa;Lord, Joanne L.;Albers, Colleen S.;Petersen, Ronald;Mason, Sara S.;Knopman, David;Johnson, Kris;Villanueva-Meyer, Javier;Pavlik, Valory;Pacini, Nathaniel;Lamb, Ashley;Kass, Joseph S.;Doody, Rachelle S.;Shibley, Victoria;Chowdhury, Munir;Rountree, Susan;Dang, Mimi;Stern, Yaakov;Honig, Lawrence S.;Mintz, Akiva;Ances, Beau;Morris, John C.;Winkfield, David;Carroll, Maria;Stobbs-Cucchi, Georgia;Oliver, Angela;Creech, Mary L.;Mintun, Mark A.;Schneider, Stacy;Geldmacher, David;Love, Marissa Natelson;Griffith, Randall;Clark, David;Brockington, John;Marson, Daniel;Grossman, Hillel;Goldstein, Martin A.;Greenberg, Jonathan;Mitsis, Effie;Shah, Raj C.;Lamar, Melissa;Samuels, Patricia;Duara, Ranjan;Greig-Custo, Maria T.;Rodriguez, Rosemarie;Albert, Marilyn;Onyike, Chiadi;Farrington, Leonie;Rudow, Scott;Brichko, Rottislav;Kielb, Stephanie;Smith, Amanda;Raj, Balebail Ashok;Fargher, Kristin;Sadowski, Martin;Wisniewski, Thomas;Shulman, Melanie;Faustin, Arline;Rao, Julia;Castro, Karen M.;Ulysse, Anaztasia;Chen, Shannon;Doraiswamy, P. Murali;Petrella, Jeffrey R.;James, Olga;Wong, Terence Z.;Borges-Neto, Salvador;Karlawish, Jason H.;Wolk, David A.;Vaishnavi, Sanjeev;Clark, Christopher M.;Arnold, Steven E.;Smith, Charles D.;Jicha, Gregory A.;Khouli, Riham El;Raslau, Flavius D.;Lopez, Oscar L.;Oakley, MaryAnn;Simpson, Donna M.;Porsteinsson, Anton P.;Martin, Kim;Kowalski, Nancy;Keltz, Melanie;Goldstein, Bonnie S.;Makino, Kelly M.;Ismail, M. Saleem;Brand, Connie;Thai, Gaby;Pierce, Aimee;Yanez, Beatriz;Sosa, Elizabeth;Witbracht, Megan;Kelley, Brendan;Nguyen, Trung;Womack, Kyle;Mathews, Dana;Quiceno, Mary;Levey, Allan I.;Lah, James J.;Hajjar, Ihab;Burns, Jeffrey M.;Swerdlow, Russell H.;Brooks, William M.;Silverman, Daniel H. S.;Kremen, Sarah;Apostolova, Liana;Tingus, Kathleen;Lu, Po H.;Bartzokis, George;Woo, Ellen;Teng, Edmond;Graff-Radford, Neill R.;Parfitt, Francine;Poki-Walker, Kim;Farlow, Martin R.;Hake, Ann Marie;Matthews, Brandy R.;Brosch, Jared R.;Herring, Scott;van Dyck, Christopher H.;Mecca, Adam P.;Good, Susan P.;MacAvoy, Martha G.;Carson, Richard E.;Varma, Pradeep;Chertkow, Howard;Vaitekunas, Susan;Hosein, Chris;Black, Sandra;Stefanovic, Bojana;Heyn, Chris;Hsiung, Ging-Yuek Robin;Kim, Ellen;Mudge, Benita;Sossi, Vesna;Feldman, Howard;Assaly, Michele;Finger, Elizabeth;Pasternak, Stephen;Rachinsky, Irina;Kertesz, Andrew;Drost, Dick;Rogers, John;Grant, Ian;Muse, Brittanie;Rogalski, Emily;Robson, Jordan;Mesulam, M. -Marsel;Kerwin, Diana;Wu, Chuang-Kuo;Johnson, Nancy;Lipowski, Kristine;Weintraub, Sandra;Bonakdarpour, Borna;Pomara, Nunzio;Hernando, Raymundo;Sarrael, Antero;Rosen, Howard J.;Miller, Bruce L.;Weiner, Micheal W.;Perry, David;Turner, Raymond Scott;Johnson, Kathleen;Reynolds, Brigid;MCCann, Kelly;Poe, Jessica;Marshall, Gad A.;Sperling, Reisa A.;Johnson, Keith A.;Yesavage, Jerome;Taylor, Joy L.;Chao, Steven;Coleman, Jaila;White, Jessica D.;Lane, Barton;Rosen, Allyson;Tinklenberg, Jared;Belden, Christine M.;Atri, Alireza;Spann, Bryan M.;Clark, Kelly A.;Zamrini, Edward;Sabbagh, Marwan;Killiany, Ronald;Stern, Robert;Mez, Jesse;Kowall, Neil;Budson, Andrew E.;Obisesan, Thomas O.;Ntekim, Oyonumo E.;Wolday, Saba;Khan, Javed I.;Nwulia, Evaristus;Nadarajah, Sheeba;Lerner, Alan;Ogrocki, Paula;Tatsuoka, Curtis;Fatica, Parianne;Fletcher, Evan;Maillard, Pauline;Olichney, John;DeCarli, Charles;Carmichael, Owen;Bates, Vernice;Capote, Horacio;Rainka, Michelle;Borrie, Michael;Lee, T. -Y.;Bartha, Rob;Johnson, Sterling;Asthana, Sanjay;Carlsson, Cynthia M.;Perrin, Allison;Burke, Anna;Scharre, Douglas W.;Kataki, Maria;Tarawneh, Rawan;Kelley, Brendan;Hart, David;Zimmerman, Earl A.;Celmins, Dzintra;Miller, Delwyn D.;Ponto, Laura L. Boles;Smith, Karen Ekstam;Koleva, Hristina;Shim, Hyungsub;Nam, Ki Won;Schultz, Susan K.;Williamson, Jeff D.;Craft, Suzanne;Cleveland, Jo;Yang, Mia;Sink, Kaycee M.;Ott, Brian R.;Drake, Jonathan;Tremont, Geoffrey;Daiello, Lori A.;Drake, Jonathan D.;Sabbagh, Marwan;Ritter, Aaron;Bernick, Charles;Munic, Donna;Mintz, Akiva;O'Connelll, Abigail;Mintzer, Jacobo;Wiliams, Arthur;Masdeu, Joseph;Shi, Jiong;Garcia, Angelica;Sabbagh, Marwan;Newhouse, Paul;Potkin, Steven;Salloway, Stephen;Malloy, Paul;Correia, Stephen;Kittur, Smita;Pearlson, Godfrey D.;Blank, Karen;Anderson, Karen;Flashman, Laura A.;Seltzer, Marc;Hynes, Mary L.;Santulli, Robert B.;Relkin, Norman;Chiang, Gloria;Lee, Athena;Lin, Michael;Ravdin, Lisa;null, null
2023-01-01
Abstract
Background: Increasing research suggests that gait abnormalities can be a risk factor for Alzheimer's Disease (AD). Notably, there is growing evidence highlighting this risk factor in individuals with amnestic Mild Cognitive Impairment (aMCI), however further studies are needed. The aim of this study is to analyze cognitive tests results and brain-related measures over time in aMCI and examine how the presence of gait abnormalities (neurological or orthopedic) or normal gait affects these trends. Additionally, we sought to assess the significance of gait and gait-related measures as prognostic indicators for the progression from aMCI to AD dementia, comparing those who converted to AD with those who remained with a stable aMCI diagnosis during the follow-up. Methods: Four hundred two individuals with aMCI from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were included. Robust linear mixed-effects models were used to study the impact of gait abnormalities on a comprehensive neuropsychological battery over 36 months while controlling for relevant medical variables at baseline. The impact of gait on brain measures was also investigated. Lastly, the Cox proportional-hazards model was used to explore the prognostic relevance of abnormal gait and neuropsychological associated tests. Results: While controlling for relevant covariates, we found that gait abnormalities led to a greater decline over time in attention (DSST) and global cognition (MMSE). Intriguingly, psychomotor speed (TMT-A) and divided attention (TMT-B) declined uniquely in the abnormal gait group. Conversely, specific AD global cognition tests (ADAS-13) and auditory-verbal memory (RAVLT immediate recall) declined over time independently of gait profile. All the other cognitive tests were not significantly affected by time or by gait profile. In addition, we found that ventricles size increased faster in the abnormal gait group compared to the normal gait group. In terms of prognosis, abnormal gait (HR = 1.7), MMSE (HR = 1.09), and DSST (HR = 1.03) covariates showed a higher impact on AD dementia conversion. Conclusions: The importance of the link between gait and related cognitive functions in terms of diagnosis, prognosis, and rehabilitation in aMCI is critical. We showed that in aMCI gait abnormalities lead to executive functions/attention deterioration and conversion to AD dementia.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11389/55235
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Il report seguente simula gli indicatori relativi alla propria produzione scientifica in relazione alle soglie ASN 2023-2025 del proprio SC/SSD. Si ricorda che il superamento dei valori soglia (almeno 2 su 3) è requisito necessario ma non sufficiente al conseguimento dell'abilitazione. La simulazione si basa sui dati IRIS e sugli indicatori bibliometrici alla data indicata e non tiene conto di eventuali periodi di congedo obbligatorio, che in sede di domanda ASN danno diritto a incrementi percentuali dei valori. La simulazione può differire dall'esito di un’eventuale domanda ASN sia per errori di catalogazione e/o dati mancanti in IRIS, sia per la variabilità dei dati bibliometrici nel tempo. Si consideri che Anvur calcola i valori degli indicatori all'ultima data utile per la presentazione delle domande.
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