Emily C Edmonds1, Alexandra J Weigand2, Sean N Hatton2, Anisa J Marshall2, Kelsey R Thomas2, Daniela A Ayala2, Mark W Bondi2, Carrie R McDonald2. 1. From the Veterans Affairs San Diego Healthcare System (E.C.E., K.R.T., M.W.B.); Department of Psychiatry (E.C.E., S.N.H., K.R.T., M.W.B., C.R.M.), Center for Multimodal Imaging and Genetics (S.N.H., A.M., C.R.M.), Department of Neurosciences (S.N.H.), and Center for Behavior Genetics of Aging (S.N.H.), University of California San Diego, La Jolla; Joint Doctoral Program in Clinical Psychology (A.J.W., J.E.), San Diego State University/University of California San Diego; Department of Psychology (A.J.M.), University of Southern California, Los Angeles; and Department of Biology (D.A.A.), San Diego State University, CA. ecedmonds@ucsd.edu. 2. From the Veterans Affairs San Diego Healthcare System (E.C.E., K.R.T., M.W.B.); Department of Psychiatry (E.C.E., S.N.H., K.R.T., M.W.B., C.R.M.), Center for Multimodal Imaging and Genetics (S.N.H., A.M., C.R.M.), Department of Neurosciences (S.N.H.), and Center for Behavior Genetics of Aging (S.N.H.), University of California San Diego, La Jolla; Joint Doctoral Program in Clinical Psychology (A.J.W., J.E.), San Diego State University/University of California San Diego; Department of Psychology (A.J.M.), University of Southern California, Los Angeles; and Department of Biology (D.A.A.), San Diego State University, CA.
Abstract
OBJECTIVE: We previously identified 4 empirically derived mild cognitive impairment (MCI) subtypes via cluster analysis within the Alzheimer's Disease Neuroimaging Initiative (ADNI) and demonstrated high correspondence between patterns of cortical thinning at baseline and each cognitive subtype. We aimed to determine whether our MCI subtypes demonstrate unique longitudinal atrophy patterns. METHODS: ADNI participants (295 with MCI and 134 cognitively normal [CN]) underwent annual structural MRI and neuropsychological assessments. General linear modeling compared vertex-wise differences in cortical atrophy rates between each MCI subtype and the CN group. Linear mixed models examined trajectories of cortical atrophy over 3 years within lobar regions of interest. RESULTS: Compared to the CN group, those with amnestic MCI (memory deficit) initially demonstrated greater atrophy rates within medial temporal lobe regions that became more widespread over time. Those with dysnomic/amnestic MCI (naming/memory deficits) showed greater atrophy rates largely localized to temporal lobe regions. The mixed MCI (impairment in all cognitive domains) group showed greater atrophy rates in widespread regions at all time points. The cluster-derived normal group, who had intact neuropsychological performance and normal cortical thickness at baseline despite their MCI diagnosis via conventional diagnostic criteria, continued to show normal cognition and minimal cortical atrophy over 3 years. CONCLUSIONS: ADNI's purported amnestic MCI sample produced more refined cognitive subtypes with unique longitudinal cortical atrophy rates. These novel MCI subtypes reliably reflect underlying atrophy, reduce false-positive diagnostic errors, and improve prediction of clinical course. Such improvements have implications for the selection of participants for clinical trials and for providing more precise risk assessment for individuals diagnosed with MCI.
OBJECTIVE: We previously identified 4 empirically derived mild cognitive impairment (MCI) subtypes via cluster analysis within the Alzheimer's Disease Neuroimaging Initiative (ADNI) and demonstrated high correspondence between patterns of cortical thinning at baseline and each cognitive subtype. We aimed to determine whether our MCI subtypes demonstrate unique longitudinal atrophy patterns. METHODS: ADNI participants (295 with MCI and 134 cognitively normal [CN]) underwent annual structural MRI and neuropsychological assessments. General linear modeling compared vertex-wise differences in cortical atrophy rates between each MCI subtype and the CN group. Linear mixed models examined trajectories of cortical atrophy over 3 years within lobar regions of interest. RESULTS: Compared to the CN group, those with amnestic MCI (memory deficit) initially demonstrated greater atrophy rates within medial temporal lobe regions that became more widespread over time. Those with dysnomic/amnestic MCI (naming/memory deficits) showed greater atrophy rates largely localized to temporal lobe regions. The mixed MCI (impairment in all cognitive domains) group showed greater atrophy rates in widespread regions at all time points. The cluster-derived normal group, who had intact neuropsychological performance and normal cortical thickness at baseline despite their MCI diagnosis via conventional diagnostic criteria, continued to show normal cognition and minimal cortical atrophy over 3 years. CONCLUSIONS: ADNI's purported amnestic MCI sample produced more refined cognitive subtypes with unique longitudinal cortical atrophy rates. These novel MCI subtypes reliably reflect underlying atrophy, reduce false-positive diagnostic errors, and improve prediction of clinical course. Such improvements have implications for the selection of participants for clinical trials and for providing more precise risk assessment for individuals diagnosed with MCI.
Authors: Carrie R McDonald; Lusineh Gharapetian; Linda K McEvoy; Christine Fennema-Notestine; Donald J Hagler; Dominic Holland; Anders M Dale Journal: Neurobiol Aging Date: 2010-05-14 Impact factor: 4.673
Authors: Melissa E Murray; Neill R Graff-Radford; Owen A Ross; Ronald C Petersen; Ranjan Duara; Dennis W Dickson Journal: Lancet Neurol Date: 2011-07-27 Impact factor: 44.182
Authors: Lindsay R Clark; Lisa Delano-Wood; David J Libon; Carrie R McDonald; Daniel A Nation; Katherine J Bangen; Amy J Jak; Rhoda Au; David P Salmon; Mark W Bondi Journal: J Int Neuropsychol Soc Date: 2013-04-03 Impact factor: 2.892
Authors: Mary M Machulda; Emily S Lundt; Sabrina M Albertson; Walter K Kremers; Michelle M Mielke; David S Knopman; Mark W Bondi; Ronald C Petersen Journal: Alzheimers Dement Date: 2019-05-23 Impact factor: 21.566
Authors: Katherine J Bangen; Alexandra L Clark; Madeline Werhane; Emily C Edmonds; Daniel A Nation; Nicole Evangelista; David J Libon; Mark W Bondi; Lisa Delano-Wood Journal: J Alzheimers Dis Date: 2016-03-29 Impact factor: 4.472
Authors: Joel S Eppig; Emily C Edmonds; Laura Campbell; Mark Sanderson-Cimino; Lisa Delano-Wood; Mark W Bondi Journal: J Int Neuropsychol Soc Date: 2017-06-05 Impact factor: 2.892
Authors: Emily C Edmonds; Joel Eppig; Mark W Bondi; Kelly M Leyden; Bailey Goodwin; Lisa Delano-Wood; Carrie R McDonald Journal: Neurology Date: 2016-10-19 Impact factor: 9.910
Authors: David M Cash; Gerard R Ridgway; Yuying Liang; Natalie S Ryan; Kirsi M Kinnunen; Thomas Yeatman; Ian B Malone; Tammie L S Benzinger; Clifford R Jack; Paul M Thompson; Bernardino F Ghetti; Andrew J Saykin; Colin L Masters; John M Ringman; Stephen P Salloway; Peter R Schofield; Reisa A Sperling; Nigel J Cairns; Daniel S Marcus; Chengjie Xiong; Randall J Bateman; John C Morris; Martin N Rossor; Sébastien Ourselin; Nick C Fox Journal: Neurology Date: 2013-09-18 Impact factor: 9.910
Authors: Emily C Edmonds; Denis S Smirnov; Kelsey R Thomas; Lisa V Graves; Katherine J Bangen; Lisa Delano-Wood; Douglas R Galasko; David P Salmon; Mark W Bondi Journal: Neurology Date: 2021-08-10 Impact factor: 11.800
Authors: Marc Norman; Sarah J Wilson; Sallie Baxendale; William Barr; Cady Block; Robyn M Busch; Alberto Fernandez; Erik Hessen; David W Loring; Carrie R McDonald; Bruce P Hermann Journal: Epilepsia Open Date: 2021-03-02
Authors: Dallas P Veitch; Michael W Weiner; Paul S Aisen; Laurel A Beckett; Charles DeCarli; Robert C Green; Danielle Harvey; Clifford R Jack; William Jagust; Susan M Landau; John C Morris; Ozioma Okonkwo; Richard J Perrin; Ronald C Petersen; Monica Rivera-Mindt; Andrew J Saykin; Leslie M Shaw; Arthur W Toga; Duygu Tosun; John Q Trojanowski Journal: Alzheimers Dement Date: 2021-09-28 Impact factor: 16.655
Authors: Eleanor L S Conole; Anna J Stevenson; Susana Muñoz Maniega; Sarah E Harris; Claire Green; Maria Del C Valdés Hernández; Mathew A Harris; Mark E Bastin; Joanna M Wardlaw; Ian J Deary; Veronique E Miron; Heather C Whalley; Riccardo E Marioni; Simon R Cox Journal: Neurology Date: 2021-11-17 Impact factor: 11.800
Authors: Haakon R Hol; Marianne M Flak; Linda Chang; Gro Christine Christensen Løhaugen; Knut Jørgen Bjuland; Lars M Rimol; Andreas Engvig; Jon Skranes; Thomas Ernst; Bengt-Ove Madsen; Susanne S Hernes Journal: Front Aging Neurosci Date: 2022-04-04 Impact factor: 5.702