A cognitive electrophysiological signature differentiates amnestic mild cognitive impairment from normal aging

Li, Juan; Broster, Lucas S.; Jicha, Gregory A.; Munro, Nancy B.; Schmitt, Frederick A.; Abner, Erin; Kryscio, Richard; Smith, Charles D.; Jiang, Yang

doi:10.1186/s13195-016-0229-3

A cognitive electrophysiological signature differentiates amnestic mild cognitive impairment from normal aging

Journal Article · Thu Jan 19 00:00:00 EST 2017 · Alzheimer's Research & Therapy

DOI:https://doi.org/10.1186/s13195-016-0229-3· OSTI ID:1627019

Li, Juan ^[1]; Broster, Lucas S. ^[2]; Jicha, Gregory A. ^[2]; Munro, Nancy B. ^[3]; Schmitt, Frederick A. ^[2]; Abner, Erin ^[2]; Kryscio, Richard ^[2]; Smith, Charles D. ^[2]; Jiang, Yang ^[2]

Chinese Academy of Sciences (CAS), Beijing (China); Univ. of Kentucky, Lexington, KY (United States); DOE/OSTI
Univ. of Kentucky, Lexington, KY (United States)
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

Background: Noninvasive and effective biomarkers for early detection of amnestic mild cognitive impairment (aMCI) before measurable changes in behavioral performance remain scarce. Cognitive event-related potentials (ERPs) measure synchronized synaptic neural activity associated with a cognitive event. Loss of synapses is a hallmark of the neuropathology of early Alzheimer’s disease (AD). In the present study, we tested the hypothesis that ERP responses during working memory retrieval discriminate aMCI from cognitively normal controls (NC) matched in age and education. Methods: Eighteen NC, 17 subjects with aMCI, and 13 subjects with AD performed a delayed match-to-sample task specially designed not only to be easy enough for impaired participants to complete but also to generate comparable performance between subjects with NC and those with aMCI. Scalp electroencephalography, memory accuracy, and reaction times were measured. Results: Whereas memory performance separated the AD group from the others, the performance of NC and subjects with aMCI was similar. In contrast, left frontal cognitive ERP patterns differentiated subjects with aMCI from NC. Enhanced P3 responses at left frontal sites were associated with nonmatching relative to matching stimuli during working memory tasks in patients with aMCI and AD, but not in NC. The accuracy of discriminating aMCI from NC was 85% by using left frontal match/nonmatch effect combined with nonmatch reaction time. Conclusions: The left frontal cognitive ERP indicator holds promise as a sensitive, simple, affordable, and noninvasive biomarker for detection of early cognitive impairment.

View Accepted Manuscript (DOE)

Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: China Abroad Scholarship Fund; Chinese Academy of Sciences and State Administration of Foreign Experts Affairs (CAS/SAFEA); National Institutes of Health (NIH); National Science Foundation of China; USDOE Office of Science (SC); University of Kentucky Department of Behavioral Science

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 1627019

Journal Information:: Alzheimer's Research & Therapy, Journal Name: Alzheimer's Research & Therapy Journal Issue: 1 Vol. 9; ISSN 1758-9193

Publisher:: BioMed CentralCopyright Statement

Country of Publication:: United States

Language:: English

References (50)

Impact of clinical symptoms and diagnosis: The electronic Person‐Specific Outcome Measure (ePSOM) development programme Saunders, Stina; Muñiz‐Terrera, Graciela; Sheehan, Shane Alzheimer's & Dementia, Vol. 17, Issue S9 https://doi.org/10.1002/alz.053791	journal	December 2021
Functional response in ventral temporal cortex differentiates mild cognitive impairment from normal aging Gold, Brian T.; Jiang, Yang; Jicha, Greg A. Human Brain Mapping https://doi.org/10.1002/hbm.20932	journal	January 2009
Resting EEG Discrimination of Early Stage Alzheimer’s Disease from Normal Aging Using Inter-Channel Coherence Network Graphs McBride, Joseph; Zhao, Xiaopeng; Munro, Nancy Annals of Biomedical Engineering, Vol. 41, Issue 6 https://doi.org/10.1007/s10439-013-0788-4	journal	March 2013
Absent event-related potential (ERP) word repetition effects in mild Alzheimer's disease Olichney, John M.; Iragui, Vicente J.; Salmon, David P. Clinical Neurophysiology, Vol. 117, Issue 6 https://doi.org/10.1016/j.clinph.2006.02.022	journal	June 2006
Electroencephalography and event-related potentials as biomarkers of mild cognitive impairment and mild Alzheimer's disease Jackson, Colleen E.; Snyder, Peter J. Alzheimer's & Dementia, Vol. 4, Issue 1S1 https://doi.org/10.1016/j.jalz.2007.10.008	journal	December 2007
Atypical event-related potentials in patients with mild cognitive impairment: An identification-priming study Galli, Giulia; Ragazzoni, Aldo; Viggiano, Maria Pia Alzheimer's & Dementia, Vol. 6, Issue 4 https://doi.org/10.1016/j.jalz.2009.05.664	journal	July 2010
The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer's disease McKhann, Guy M.; Knopman, David S.; Chertkow, Howard Alzheimer's & Dementia, Vol. 7, Issue 3 https://doi.org/10.1016/j.jalz.2011.03.005	journal	May 2011
Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive impairment Scheff, Stephen W.; Price, Douglas A.; Schmitt, Frederick A. Neurobiology of Aging, Vol. 27, Issue 10 https://doi.org/10.1016/j.neurobiolaging.2005.09.012	journal	October 2006
Brain ERP components predict which individuals progress to Alzheimer's disease and which do not Chapman, Robert M.; McCrary, John W.; Gardner, Margaret N. Neurobiology of Aging, Vol. 32, Issue 10 https://doi.org/10.1016/j.neurobiolaging.2009.11.010	journal	October 2011
Age effects on brain activity during repetition priming of targets and distracters Lawson, Adam L.; Guo, Chunyan; Jiang, Yang Neuropsychologia, Vol. 45, Issue 6 https://doi.org/10.1016/j.neuropsychologia.2006.10.014	journal	January 2007
Distinct neural mechanisms for repetition effects of visual objects Guo, C.; Lawson, A. L.; Jiang, Y. Neuroscience, Vol. 149, Issue 4 https://doi.org/10.1016/j.neuroscience.2007.07.060	journal	November 2007
Active maintenance in prefrontal area 46 creates distractor-resistant memory Sakai, Katsuyuki; Rowe, James B.; Passingham, Richard E. Nature Neuroscience, Vol. 5, Issue 5 https://doi.org/10.1038/nn846	journal	April 2002
Repeated retrieval during working memory is sensitive to amnestic mild cognitive impairment Broster, Lucas S.; Li, Juan; Smith, Charles D. Journal of Clinical and Experimental Neuropsychology, Vol. 35, Issue 9 https://doi.org/10.1080/13803395.2013.838942	journal	November 2013
Early Event-Related Potential Changes During Working Memory Activation Predict Rapid Decline in Mild Cognitive Impairment Missonnier, P.; Gold, G.; Fazio-Costa, L. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, Vol. 60, Issue 5 https://doi.org/10.1093/gerona/60.5.660	journal	May 2005
Mild cognitive impairment - beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment Winblad, B.; Palmer, K.; Kivipelto, M. Journal of Internal Medicine, Vol. 256, Issue 3 https://doi.org/10.1111/j.1365-2796.2004.01380.x	journal	September 2004
Mild cognitive impairment as a diagnostic entity Petersen, R. C. Journal of Internal Medicine, Vol. 256, Issue 3 https://doi.org/10.1111/j.1365-2796.2004.01388.x	journal	September 2004
Synaptic Theory of Working Memory Mongillo, G.; Barak, O.; Tsodyks, M. Science, Vol. 319, Issue 5869 https://doi.org/10.1126/science.1150769	journal	March 2008
Complementary Neural Mechanisms for Tracking Items in Human Working Memory Jiang, Y. Science, Vol. 287, Issue 5453 https://doi.org/10.1126/science.287.5453.643	journal	January 2000
Parallel neuronal mechanisms for short-term memory Miller, E.; Desimone, R. Science, Vol. 263, Issue 5146 https://doi.org/10.1126/science.8290960	journal	January 1994
Abnormal verbal event related potentials in mild cognitive impairment and incipient Alzheimer's disease Olichney, J. M. Journal of Neurology, Neurosurgery & Psychiatry, Vol. 73, Issue 4 https://doi.org/10.1136/jnnp.73.4.377	journal	October 2002
Patients with MCI and N400 or P600 abnormalities are at very high risk for conversion to dementia Olichney, J. M.; Taylor, J. R.; Gatherwright, J. Neurology, Vol. 70, Issue Issue 19, Part 2 https://doi.org/10.1212/01.wnl.0000281689.28759.ab	journal	December 2007
Event-related potential markers of brain changes in preclinical familial Alzheimer disease Quiroz, Y. T.; Ally, B. A.; Celone, K. Neurology, Vol. 77, Issue 5 https://doi.org/10.1212/wnl.0b013e318227b1b0	journal	August 2011
University of Kentucky Sanders-Brown Healthy Brain Aging Volunteers: Donor Characteristics, Procedures and Neuropathology A. Schmitt, Frederick; T. Nelson, Peter; Abner, Erin Current Alzheimer Research, Vol. 9, Issue 6 https://doi.org/10.2174/156720512801322591	journal	June 2012
Initial Experience in Using Continuous Arterial Spin-Labeled MR Imaging for Early Detection of Alzheimer Disease Raji, C. A.; Lee, C.; Lopez, O. L. American Journal of Neuroradiology, Vol. 31, Issue 5 https://doi.org/10.3174/ajnr.a1955	journal	January 2010
Synapse Stability in the Precuneus Early in the Progression of Alzheimer's Disease Scheff, Stephen W.; Price, Douglas A.; Schmitt, Frederick A. Journal of Alzheimer's Disease, Vol. 35, Issue 3 https://doi.org/10.3233/jad-122353	journal	May 2013
Synaptic Change in the Posterior Cingulate Gyrus in the Progression of Alzheimer's Disease Scheff, Stephen W.; Price, Douglas A.; Ansari, Mubeen A. Journal of Alzheimer's Disease, Vol. 43, Issue 3 https://doi.org/10.3233/jad-141518	journal	December 2014
Cognitive Event-Related Potentials: Biomarkers of Synaptic Dysfunction Across the Stages of Alzheimer's Disease Olichney, John M.; Yang, Jin-Chen; Taylor, Jason Journal of Alzheimer's Disease, Vol. 26, Issue s3 https://doi.org/10.3233/jad-2011-0047	journal	October 2011
Alzheimer’s Biomarkers are Correlated with Brain Connectivity in Older Adults Differentially during Resting and Task States Jiang, Yang; Huang, Haiqing; Abner, Erin Frontiers in Aging Neuroscience, Vol. 8 https://doi.org/10.3389/fnagi.2016.00015	journal	February 2016
Attempted and Successful Compensation in Preclinical and Early Manifest Neurodegeneration â€“ A Review of Task fMRI Studies Scheller, Elisa; Minkova, Lora; Leitner, Mathias Frontiers in Psychiatry, Vol. 5 https://doi.org/10.3389/fpsyt.2014.00132	journal	September 2014
Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria Bruno, Dubois,; H., Feldman, Howard; Claudia, Jacova, Columbia University https://doi.org/10.7916/dg3n-mf18	text	January 2014
Brain potentials distinguish new and studied objects during working memory Guo, Chunyan; Lawson, Adam L.; Zhang, Qin Human Brain Mapping, Vol. 29, Issue 4 https://doi.org/10.1002/hbm.20409	journal	January 2008
Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria Dubois, Bruno; Feldman, Howard H.; Jacova, Claudia The Lancet Neurology, Vol. 13, Issue 6 https://doi.org/10.1016/S1474-4422(14)70090-0	journal	June 2014
Spectral and complexity analysis of scalp EEG characteristics for mild cognitive impairment and early Alzheimer's disease McBride, Joseph C.; Zhao, Xiaopeng; Munro, Nancy B. Computer Methods and Programs in Biomedicine, Vol. 114, Issue 2 https://doi.org/10.1016/j.cmpb.2014.01.019	journal	April 2014
Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease Sperling, Reisa A.; Aisen, Paul S.; Beckett, Laurel A. Alzheimer's & Dementia, Vol. 7, Issue 3 https://doi.org/10.1016/j.jalz.2011.03.003	journal	May 2011
The diagnosis of mild cognitive impairment due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease Albert, Marilyn S.; DeKosky, Steven T.; Dickson, Dennis Alzheimer's & Dementia, Vol. 7, Issue 3 https://doi.org/10.1016/j.jalz.2011.03.008	journal	April 2011
Brain event-related potentials: Diagnosing early-stage Alzheimer's disease Chapman, Robert M.; Nowlis, Geoffrey H.; McCrary, John W. Neurobiology of Aging, Vol. 28, Issue 2 https://doi.org/10.1016/j.neurobiolaging.2005.12.008	journal	February 2007
A standardized set of 260 pictures: Norms for name agreement, image agreement, familiarity, and visual complexity. Snodgrass, Joan G.; Vanderwart, Mary Journal of Experimental Psychology: Human Learning & Memory, Vol. 6, Issue 2 https://doi.org/10.1037//0278-7393.6.2.174	journal	January 1980
A standardized set of 260 pictures: Norms for name agreement, image agreement, familiarity, and visual complexity. Snodgrass, Joan G.; Vanderwart, Mary Journal of Experimental Psychology: Human Learning and Memory, Vol. 6, Issue 2 https://doi.org/10.1037/0278-7393.6.2.174	journal	January 1980
Abnormal P600 word repetition effect in elderly persons with preclinical Alzheimer’s disease Olichney, John M.; Pak, Jamie; Salmon, David P. Cognitive Neuroscience, Vol. 4, Issue 3-4 https://doi.org/10.1080/17588928.2013.838945	journal	October 2013
The Uniform Data Set (UDS): Clinical and Cognitive Variables and Descriptive Data From Alzheimer Disease Centers Morris, John C.; Weintraub, Sandra; Chui, Helena C. Alzheimer Disease & Associated Disorders, Vol. 20, Issue 4 https://doi.org/10.1097/01.wad.0000213865.09806.92	journal	January 2006
Clinical Features of Mild Cognitive Impairment Differ in the Research and Tertiary Clinic Settings Jicha, G. A.; Abner, E.; Schmitt, F. A. Dementia and Geriatric Cognitive Disorders, Vol. 26, Issue 2 https://doi.org/10.1159/000151635	journal	January 2008
The Diagnosis of Mild Cognitive Impairment due to Alzheimer’s Disease: Recommendations from the National Institute on Aging-Alzheimer’s Association Workgroups on Diagnostic Guidelines for Alzheimer’s Disease Albert, Marilyn S.; DeKosky, Steven T.; Dickson, Dennis FOCUS, Vol. 11, Issue 1 https://doi.org/10.1176/appi.focus.11.1.96	journal	January 2013
Event-related potential markers of brain changes in preclinical familial Alzheimer disease Quiroz, Y. T.; Ally, B. A.; Celone, K. Neurology, Vol. 77, Issue 5 https://doi.org/10.1212/WNL.0b013e318227b1b0	journal	August 2011
"Preclinical" AD revisited: Neuropathology of cognitively normal older adults Schmitt, F. A.; Davis, D. G.; Wekstein, D. R. Neurology, Vol. 55, Issue 3 https://doi.org/10.1212/WNL.55.3.370	journal	August 2000
Eye movement analysis and cognitive processing: detecting indicators of conversion to Alzheimer’s disease Gonçalves de Freitas Pereira, Marta Luísa; von Zuben de Arruda Camargo, Marina; Aprahamian, Ivan Neuropsychiatric Disease and Treatment https://doi.org/10.2147/NDT.S55371	journal	July 2014
Initial Experience in Using Continuous Arterial Spin-Labeled MR Imaging for Early Detection of Alzheimer Disease Raji, C. A.; Lee, C.; Lopez, O. L. American Journal of Neuroradiology, Vol. 31, Issue 5 https://doi.org/10.3174/ajnr.A1955	journal	January 2010
Synapse Stability in the Precuneus Early in the Progression of Alzheimer's Disease Scheff, Stephen W.; Price, Douglas A.; Schmitt, Frederick A. Journal of Alzheimer's Disease, Vol. 35, Issue 3 https://doi.org/10.3233/JAD-122353	journal	May 2013
Synaptic Change in the Posterior Cingulate Gyrus in the Progression of Alzheimer's Disease Scheff, Stephen W.; Price, Douglas A.; Ansari, Mubeen A. Journal of Alzheimer's Disease, Vol. 43, Issue 3 https://doi.org/10.3233/JAD-141518	journal	December 2014
Cognitive Event-Related Potentials: Biomarkers of Synaptic Dysfunction Across the Stages of Alzheimer's Disease Olichney, John M.; Yang, Jin-Chen; Taylor, Jason Journal of Alzheimer's Disease, Vol. 26, Issue s3 https://doi.org/10.3233/JAD-2011-0047	journal	October 2011
Toward Defining the Preclinical Stages of Alzheimer's Disease: Recommendations from the National Institute on Aging-Alzheimer's Association Workgroups on Diagnostic Guidelines for Alzheimer's Disease Sperling, Reisa A.; Aisen, Paul S.; Beckett, Laurel A. Columbia University https://doi.org/10.7916/d8wm2rx8	text	January 2011

Cited By (7)

Electrophysiological repetition effects in persons with mild cognitive impairment depend upon working memory demand Broster, Lucas S.; Jenkins, Shonna L.; Holmes, Sarah D. Neuropsychologia, Vol. 117 https://doi.org/10.1016/j.neuropsychologia.2018.05.001	journal	August 2018
Alpha desynchronization during simple working memory unmasks pathological aging in cognitively healthy individuals Arakaki, Xianghong; Lee, Ryan; King, Kevin S. PLOS ONE, Vol. 14, Issue 1 https://doi.org/10.1371/journal.pone.0208517	journal	January 2019
Functional human GRIN2B promoter polymorphism and variation of mental processing speed in older adults Jiang, Yang; Lin, Ming Kuan; Jicha, Gregory A. Aging, Vol. 9, Issue 4 https://doi.org/10.18632/aging.101228	journal	April 2017
Tuning Up the Old Brain with New Tricks: Attention Training via Neurofeedback Jiang, Yang; Abiri, Reza; Zhao, Xiaopeng Frontiers in Aging Neuroscience, Vol. 9 https://doi.org/10.3389/fnagi.2017.00052	journal	March 2017
Discriminating Fake From True Brain Injury Using Latency of Left Frontal Neural Responses During Old/New Memory Recognition Neal, Jennifer; Strothkamp, Stephanie; Bedingar, Esias Frontiers in Neuroscience, Vol. 13 https://doi.org/10.3389/fnins.2019.00988	journal	September 2019
Acute Exercise Facilitates the N450 Inhibition Marker and P3 Attention Marker during Stroop Test in Young and Older Adults Hsieh, Shu-Shih; Huang, Chung-Ju; Wu, Chien-Ting Journal of Clinical Medicine, Vol. 7, Issue 11 https://doi.org/10.3390/jcm7110391	journal	October 2018
Spared behavioral repetition effects in Alzheimer’s disease linked to an altered neural mechanism at posterior cortex Broster, Lucas S.; Li, Juan; Wagner, Benjamin Journal of Clinical and Experimental Neuropsychology, Vol. 40, Issue 8 https://doi.org/10.1080/13803395.2018.1430230	journal	February 2018

Similar Records

Memory-Related Frontal Brainwaves Predict Transition to Mild Cognitive Impairment in Healthy Older Individuals Five Years Before Diagnosis

Journal Article · Mon Jan 18 19:00:00 EST 2021 · Journal of Alzheimer's Disease · OSTI ID:1787481

Discrimination of Mild Cognitive Impairment and Alzheimer′s Disease Using Transfer Entropy Measures of Scalp EEG

Journal Article · Sun Feb 22 19:00:00 EST 2015 · Journal of Healthcare Engineering · OSTI ID:2370563

Related Subjects

60 APPLIED LIFE SCIENCES
Neurosciences & Neurology

A cognitive electrophysiological signature differentiates amnestic mild cognitive impairment from normal aging

Citation Formats

References (50)

Cited By (7)

Similar Records

Related Subjects