The three most frequent forms of mild cognitive impairment (MCI) are single-domain amnestic MCI (sd-aMCI), single-domain dysexecutive MCI (sd-dMCI) and multiple-domain amnestic MCI (md-aMCI). Brain imaging differences among single domain subgroups of MCI were recently reported supporting the idea that electroencephalography (EEG) functional hallmarks can be used to differentiate these subgroups. We performed event-related potential (ERP) measures and independent component analysis in 18 sd-aMCI, 13 sd-dMCI and 35 md-aMCI cases during the successful performance of the Attentional Network Test. Sensitivity and specificity analyses of ERP for the discrimination of MCI subgroups were also made. In center-cue and spatial-cue warning stimuli, contingent negative variation (CNV) was elicited in all MCI subgroups. Two independent components (ICA1 and 2) were superimposed in the time range on the CNV. The ICA2 was strongly reduced in sd-dMCI compared to sd-aMCI and md-aMCI (4.3 vs. 7.5% and 10.9% of the CNV component). The parietal P300 ERP latency increased significantly in sd-dMCI compared to md-aMCI and sd-aMCI for both congruent and incongruent conditions. This latency for incongruent targets allowed for a highly accurate separation of sd-dMCI from both sd-aMCI and md-aMCI with correct classification rates of 90 and 81%, respectively. This EEG parameter alone performed much better than neuropsychological testing in distinguishing sd-dMCI from md-aMCI. Our data reveal qualitative changes in the composition of the neural generators of CNV in sd-dMCI. In addition, they document an increased latency of the executive P300 component that may represent a highly accurate hallmark for the discrimination of this MCI subgroup in routine clinical settings.

1.
Winblad B, Palmer K, Kivipelto M, Jelic V, Fratiglioni L, Wahlund LO, Nordberg A, Bäckman L, Albert M, Almkvist O, Arai H, Basun H, Blennow K, de Leon M, DeCarli C, Erkinjuntti T, Giacobini E, Graff C, Hardy J, Jack C, Jorm A, Ritchie K, van Duijn C, Visser P, Petersen RC: Mild cognitive impairment - beyond controversies towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med 2004;256:240-246.
2.
Petersen RC, Roberts RO, Knopman DS, Boeve BF, Geda YE, Ivnik RJ, Smith GE, Jack CR Jr: Mild cognitive impairment: ten years later. Arch Neurol 2009;66:1447-1455.
3.
Libon DJ, Xie SX, Eppig J, Wicas G, Lamar M, Lippa C, Bettcher BM, Price CC, Giovannetti T, Swenson R, Wambach DM: The heterogeneity of mild cognitive impairment: a neuropsychological analysis. J Int Neuropsychol Soc 2010;16:84-93.
4.
Petersen RC, Morris JC: Mild cognitive impairment as a clinical entity and treatment target. Arch Neurol 2005;62:1160-1163.
5.
Alexopoulos P, Greim B, Nadler K, Martens U, Krecklow B, Domes G, Herpertz S, Kurz A: Validation of the Addenbrooke's cognitive examination for detecting early Alzheimer's disease and mild vascular dementia in a German population. Dement Geriatr Cog Disord 2006;22:385-391.
6.
Mariani E, Monastero R, Mecocci P: Mild cognitive impairment: a systematic review. J Alzheimers Dis 2007;12:23-35.
7.
Rountree SD, Waring SC, Chan WC, Lupo PJ, Darby EJ, Doody RS: Importance of subtle amnestic and nonamnestic deficits in mild cognitive impairment: prognosis and conversion to dementia. Dement Geriatr Cogn Disord 2007;24:476-482.
8.
Clerici F, Del Sole A, Chiti A, Maggiore L, Lecchi M, Pomati S, Mosconi L, Lucignani G, Mariani C: Differences in hippocampal metabolism between amnestic and non-amnestic MCI subjects: automated FDG-PET image analysis. Q J Nucl Med Mol Imaging 2009;53:646-657.
9.
Jauhiainen AM, Kangasmaa T, Rusanen M, Niskanen E, Tervo S, Kivipelto M, Vanninen RL, Kuikka JT, Soininen H: Differential hypometabolism patterns according to mild cognitive impairment subtypes. Dement Geriatr Cogn Disord 2008;26:490-498.
10.
Nobili F, Frisoni GB, Portet F, Verhey F, Rodriguez G, Caroli A, Touchon J, Calvini P, Morbelli S, De Carli F, Guerra UP, Van de Pol LaVisser PJ: Brain SPECT in subtypes of mild cognitive impairment: findings from the DESCRIPA multicenter study. J Neurol 2008;255:1344-1353.
11.
Chao LL, Pa J, Duarte A, Schuff N, Weiner MW, Kramer JH, Miller BL, Freeman KM, Johnson JK: Patterns of cerebral hypoperfusion in amnestic and dysexecutive MCI. Alzheimer Dis Assoc Disord 2009;23:245-252.
12.
Wolk DA, Price JC, Saxton JA, Snitz BE, James JA, Lopez OL, Aizenstein HJ, Cohen AD, Weissfeld LA, Mathis CA, Klunk WE, De-Kosky ST: Amyloid imaging in mild cognitive impairment subtypes. Ann Neurol 2009;65:557-568.
13.
Kantarci K, Petersen RC, Przybelski SA, Weigand SD, Shiung MM, Whitwell JL, Negash S, Ivnik RJ, Boeve BF, Knopman DS, Smith GE, Jack CR Jr: Hippocampal volumes proton magnetic resonance spectroscopy metabolites and cerebrovascular disease in mild cognitive impairment subtypes. Arch Neurol 2008;65:1621-1628.
14.
Whitwell JL, Petersen RC, Negash S, Weigand SD, Kantarci K, Ivnik RJ, Knopman DS, Boeve BF, Smith GE, Jack CR Jr: Patterns of atrophy differ among specific subtypes of mild cognitive impairment. Arch Neurol 2007;64:1130-1138.
15.
Seo SW, Im K, Lee JM, Kim YH, Kim ST, Kim SY, Yang DW, Kim SI, Cho YS, Na DL: Cortical thickness in single- versus multiple-domain amnestic mild cognitive impairment. NeuroImage 2007;36:289-297.
16.
Pa J, Boxer A, Chao LL, Gazzaley A, Freeman K, Kramer J, Miller BL, Weiner MW, Neuhaus J, Johnson JK: Clinical-neuroimaging characteristics of dysexecutive mild cognitive impairment. Ann Neurol 2009;65:414-423.
17.
Chua TC, Wen W, Chen X, Kochan N, Slavin MJ, Trollor JN, Brodaty H, Sachdev PS: Diffusion tensor imaging of the posterior cingulate is a useful biomarker of mild cognitive impairment. Am J Geriatr Psychiatry 2009;17:602-613.
18.
Delano-Wood L, Bondi MW, Sacco J, Abeles N, Jak AJ, Libon DJ, Bozoki A: Heterogeneity in mild cognitive impairment: differences in neuropsychological profile and associated white matter lesion pathology. J Int Neuropsychol Soc 2009;15:906-914.
19.
Rogalski EJ, Murphy CM, deToledo-Morrell L, Shah RC, Moseley ME, Bammer R, Stebbins GT: Changes in parahippocampal white matter integrity in amnestic mild cognitive impairment: a diffusion tensor imaging study. Behav Neurol 2009;21:51-61.
20.
Zhuang L, Wen W, Zhu W, Trollor J, Kochan N, Crawford J, Reppermund S, Brodaty H, Sachdev P: White matter integrity in mild cognitive impairment: a tract-based spatial statistics study. NeuroImage 2010;53:16-25.
21.
He J, Farias S, Martinez O, Reed B, Mungas D, Charles DeCarli C: Differences in brain volume, hippocampal volume, cerebrovascular risk factors and apolipoprotein E4 among mild cognitive impairment subtypes. Arch Neurol 2009;66:1393-1399.
22.
Pa J, Boxer A, Chao LL, Gazzaley A, Freeman K, Kramer J, Miller BL, Weiner MW, Neuhaus J, Johnson JK: Clinical-neuroimaging characteristics of dysexecutive mild cognitive impairment. Ann Neurol 2009;65:414-423.
23.
Golob EJ, Irimajiri R, Starr A: Auditory cortical activity in amnestic mild cognitive impairment: relationship to subtype and conversion to dementia. Brain 2007;130:740-752.
24.
Lenzi D, Serra L, Perri R, Pantano P, Lenzi GL, Paulesu E, Caltagirone C, Bozzali M, Macaluso E: Single domain amnestic MCI: a multiple cognitive domains fMRI investigation. Neurobiol Aging 2009;32:1542-1547.
25.
Machulda MM, Senjem ML, Weigand SD, Smith GE, Ivnik RJ, Boeve BF, Knopman DS, Petersen RC, Jack CR: Functional magnetic resonance imaging changes in amnestic and nonamnestic mild cognitive impairment during encoding and recognition tasks. J Int Neuropsychol Soc 2009;15:372-382.
26.
Fan J, McCandliss BD, Sommer T, Raz A, Posner MI: Testing the efficiency and independence of attentional networks. J Cogn Neurosci 2002;14:340-347.
27.
Folstein MF, Folstein SE, McHugh PR: ‘Mini-mental state': a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189-198.
28.
Barberger-Gateau P, Chaslerie A, Dartigues JF, Commenges D, Gagnon M, Salamon R: Health measures correlates in a French elderly community population: the PAQUID study. J Gerontol 1992;47:S88-S95.
29.
Zigmond AS, Snaith RP: The hospital anxiety and depression scale. Acta Psychiatr Scand 1983;67:361-370.
30.
Wechsler D: Manual for the Wechsler Adult Intelligence Scale - revised. New York, Psychological Corporation, 1981.
31.
Reitan RM: Validity of the Trail Making Test as an indicator of organic brain damage. Percept Mot Skills 1958;8:271-276.
32.
Wechsler D: Manual for the Wechsler Adult Intelligence Scale. New York, Psychological Corporation, 1955.
33.
Milner, B: Interhemispheric differences in the localization of psychological processes in man. Br Med Bull 1971;27:272-277.
34.
Buschke H, Sliwinski MJ, Kuslansky G, Lipton RB: Diagnosis of early dementia by the Double Memory Test: encoding specificity improves diagnostic sensitivity and specificity. Neurology 1997;48:989-997.
35.
Baddeley A, Emslie H, Nimmo-Smith L: The Doors and People Test: A Test of Visual and Verbal Recall and Recognition. Bury St Edmonds, Thames Valley Test, 1994.
36.
Reitan RM: Validity of the Trail Making Test as an indicator of organic brain damage. Percept Mot Skills 1958;8:271-276.
37.
Butters N, Granholm E, Salmon DP, Grant I, Wolfe J: Episodic and semantic memory: a comparison of amnesic and demented patients. J Clin Exp Neuropsycho 1987;19:479-497.
38.
Heaton RK: Wisconsin Card Sorting Test manual. Odessa, Psychological Assessment Resources, 1981.
39.
Kaplan EF, Goodglass H, Weintraub S: The Boston Naming Test. Philadelphia, Lea and Febiger, 1983.
40.
Ghent L: Perception of overlapping and embedded figures by Children of Different Ages. Am J Psychol 1956;69:575-581.
41.
Welsh KA, Butters N, Mohs RC, Beekly D, Edland S, Fillenbaum G, Heyman A: The consortium to establish a registry for Alzheimer's disease (CERAD) - part V: a normative study of the neuropsychological battery. Neurology 1994;44:609-614.
42.
Hughes CP, Berg L, Danziger WL, Coben LA, Martin RL: A new clinical scale for the staging of dementia. Br J Psychiatr 1982;140:566-572.
43.
Morris JC, Weintraub S, Chui HC, Cummings J, DeCarli C, Ferris S, Foster NL, Galasko D, Graff-Radford N, Peskind ER, Beekly D, Ramos EM, Kukull WA: The Uniform Data Set (UDS): clinical and cognitive variables and descriptive data from Alzheimer Disease Centers. Dis Assoc Disord 2006;20:210-216.
44.
Petersen RC, Doody R, Kurz A, Mohs RC, Morris JC, Rabins PV, Ritchie K, Rossor M, Thal L, Winblad B: Current concepts in mild cognitive impairment. Arch Neurol 2001;58:1985-1992.
45.
Posner MI, Petersen SE: The attention system of the human brain. Annu Rev Neurosci 1990;13:25-42.
46.
Zappoli R: Permanent or transitory effects on neurocognitive components of the CNV complex induced by brain dysfunctions lesions and ablations in humans. Int J Psychophysiol 2003;48:189-220.
47.
Makeig S, Westerfield M, Jung TP, Covington J, Townsend J, Sejnowski TJ, Courchesne E: Functionally independent components of the late positive event-related potential during visual spatial attention. J Neurosci 1999;19:2665-2680.
48.
Makeig S, Jung TP, Bell AJ, Ghahremani D, Sejnowski TJ: Blind separation of auditory event-related brain responses into independent components. Proc Natl Acad Sci USA 1997;94:10979-10984.
49.
Milliken GA, Johnson DE: Designed experiments. New York, Van Nostrand Reinhold, 1984.
50.
Bonnet M, MacKay WA: Changes in contingent-negative variation and reaction time related to precueing of direction and force of a forearm movement. Brain Behav Evol 1989;33:147-152.
51.
Ulrich R, Leuthold H, Sommer W: Motor programming of response force and movement direction. Psychophysiology 1998;35:721-728.
52.
Neuhaus AH, Urbanek C, Opgen-Rhein C, Hahn E, Ta TM, Koehler S, Gross M, Dettling M: Event-related potentials associated with Attention Network Test. Int J Psychophysiol 2010;76:72-79.
53.
Gamboz N, Zamarian S, Cavallero C: Age-related differences in the attention network test (ANT). Exp Aging Res 2010;36:287-305.
54.
Jennings JM, Dagenbac D, Engle CM, Funke LJ: Age-related changes and the attention network task: an examination of alerting, orienting, and executive function. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 2007;14:353-369.
55.
Rueda MR, Posner MI, Rothbart MK, Davis-Stober CP: Development of the time course for processing conflict: an event-related potentials study with 4 year olds and adults. BMC Neurosci 2004;22:5-39.
56.
Rosano C, Aizenstein HJ, Cochran JL, Saxton JA, De Kosky ST, Newman AB, Kuller LH, Lopez OL, Carter CS: Event-related functional magnetic resonance imaging investigation of executive control in very old individuals with mild cognitive impairment. Biol Psychiatry 2005;57:761-777.
57.
Corbeta M, Kincade JM, Ollinger JM, McAvoy MP, Shulman GL: Voluntary orienting is dissociated from target detection in human posterior parietal cortex. Nat Neurosci 2000;3:292-297.
58.
Deiber MP, Ibáñez V, Herrmann F, Rodriguez C, Emch J, Missonnier P, Millet P, Gold G, Giannakopoulos P: Face short-term memory-related electroencephalographic patterns can differentiate multi- versus single-domain amnestic mild cognitive impairment. J Alzheimers Dis 2011;26:157-169.
59.
Bookheimer SY, Strojwas MH, Cohen MS, Saunders AM, Pericak-Vance MA, Mazziotta JC, Small GW: Patterns of brain activation in people at risk for Alzheimer's disease. N Engl J Med 2000;343:450-456.
60.
Saykin AJ, Flashman LA, Frutiger SA, Johnson SC, Mamourian AC, Moritz CH, O'Jile JR, Riordan HJ, Santulli RB, Smith CA, Weaver JB: Neuroanatomic substrates of semantic memory impairment in Alzheimer's disease: patterns of functional MRI activation. J Int Neuropsychol Soc 1999;5:377-392.
61.
Thulborn KR, Martin C, Voyvodic JT: Functional MRI imaging using a visually guided saccade paradigm for comparing activation patterns in patients with probable Alzheimer's disease and in cognitively able elderly volunteers. Am J Neuroradiol 2000;21:524-531.
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