We evaluated the relationship between brain rhythmicity and both the cerebrovascular damage (CVD) and amygdalohippocampal complex (AHC) atrophy, as revealed by scalp electroencephalography (EEG) in a cohort of subjects with mild cognitive impairment (MCI). All MCI subjects underwent EEG recording and magnetic resonance imaging. EEGs were recorded at rest. Relative power was separately computed for delta, theta, alpha1, alpha2, and alpha3 frequency bands. In the spectral band power the severity of CVD was associated with increased delta power and decreased alpha2 power. No association of vascular damage was observed with alpha3 power. Moreover, the theta/alpha1 ratio could be a reliable index for the estimation of the individual extent of CV damage. On the other side, the group with moderate hippocampal atrophy showed the highest increase of alpha2 and alpha3 power. Moreover, when the amygdalar and hippocampal volumes are separately considered, within amygdalohippocampal complex (AHC), the increase of theta/gamma ratio is best associated with amygdalar atrophy whereas alpha3/alpha2 ratio is best associated with hippocampal atrophy. CVD and AHC damages are associated with specific EEG markers. So far, these EEG markers could have a prospective value in differential diagnosis between vascular and degenerative MCI. 1. Introduction Mild cognitive impairment (MCI) is a clinical state intermediate between elderly normal cognition and dementia that affects a significant amount of the elderly population, featuring memory complaints and cognitive impairment on neuropsychological testing, but no dementia [1–3]. The hippocampus is one of the first and most affected brain regions impacted by both Alzheimer’s disease and mild cognitive impairment (MCI; [4–9]). In mild-to-moderate Alzheimer’s disease patients, it has been shown that hippocampal volumes are 27% smaller than in normal elderly controls [10, 11], whereas patients with MCI show a volume reduction of 11% [11]. So far, from a neuropathological point of view, the progression of disease from MCI state to later stages seems to follow a linear course. Nevertheless, there is some evidence from functional [12–14] and biochemical studies [15] that the process of conversion from nondemented to clinically evident demented state is not so linear. Recent fMRI studies have suggested increased medial temporal lobe (MTL) activations in MCI subjects versus controls, during the performance of memory tasks [16, 17]. Nonetheless, fMRI findings in MCI are discrepant, as MTL hypoactivation similar to that seen in AD patients
References
[1]
C. Flicker, S. H. Ferris, and B. Reisberg, “Mild cognitive impairment in the elderly: predictors of dementia,” Neurology, vol. 41, no. 7, pp. 1006–1009, 1991.
[2]
R. C. Petersen, G. E. Smith, R. J. Ivnik et al., “Apolipoprotein E status as a predictor of the development of Alzheimer's disease in memory-impaired individuals,” Journal of the American Medical Association, vol. 273, no. 16, pp. 1274–1278, 1995.
[3]
R. C. Petersen, R. Doody, A. Kurz et al., “Current concepts in mild cognitive impairment,” Archives of Neurology, vol. 58, no. 12, pp. 1985–1992, 2001.
[4]
S. E. Arnold, B. T. Hyman, J. Flory, A. R. Damasio, and G. W. Van Hoesen, “The topographical and neuroanatomical distribution of neurofibrillary tangles and neuritic plaques in the cerebral cortex of patients with alzheimer's disease,” Cerebral Cortex, vol. 1, no. 1, pp. 103–116, 1991.
[5]
M. Bobinski, J. Wegiel, H. M. Wisniewski et al., “Atrophy of Hippocampal formation subdivisions correlates with stage and duration of Alzheimer disease,” Dementia, vol. 6, no. 4, pp. 205–210, 1995.
[6]
J. L. Price and J. C. Morris, “Tangles and plaques in nondemented aging and 'preclinical' alzheimer's disease,” Annals of Neurology, vol. 45, no. 3, pp. 358–368, 1999.
[7]
B. Sch？nheit, R. Zarski, and T. G. Ohm, “Spatial and temporal relationships between plaques and tangles in Alzheimer-pathology,” Neurobiology of Aging, vol. 25, no. 6, pp. 697–711, 2004.
[8]
D. A. Bennett, J. A. Schneider, J. L. Bienias, D. A. Evans, and R. S. Wilson, “Mild cognitive impairment is related to Alzheimer disease pathology and cerebral infarctions,” Neurology, vol. 64, no. 5, pp. 834–841, 2005.
[9]
G. B. Frisoni, A. Prestia, P. E. Rasser, M. Bonetti, and P. M. Thompson, “In vivo mapping of incremental cortical atrophy from incipient to overt Alzheimer's disease,” Journal of Neurology, vol. 256, no. 6, pp. 916–924, 2009.
[10]
D. J. A. Callen, S. E. Black, F. Gao, C. B. Caldwell, and J. P. Szalai, “Beyond the hippocampus: MRI volumetry confirms widespread limbic atrophy in AD,” Neurology, vol. 57, no. 9, pp. 1669–1674, 2001.
[11]
A. T. Du, N. Schuff, D. Amend et al., “Magnetic resonance imaging of the entorhinal cortex and hippocampus in mild cognitive impairment and Alzheimer's disease,” Journal of Neurology Neurosurgery and Psychiatry, vol. 71, no. 4, pp. 441–447, 2001.
[12]
G. Gold, C. Bouras, E. K？vari et al., “Clinical validity of Braak neuropathological staging in the oldest-old,” Acta Neuropathologica, vol. 99, no. 5, pp. 579–582, 2000.
[13]
V. Della-Maggiore, W. Chau, P. R. Peres-Neto, and A. R. McIntosh, “An empirical comparison of SPM preprocessing parameters to the analysis of fMRI data,” NeuroImage, vol. 17, no. 1, pp. 19–28, 2002.
[14]
A. H？m？l？inen, M. Pihlajam？ki, H. Tanila et al., “Increased fMRI responses during encoding in mild cognitive impairment,” Neurobiology of Aging, vol. 28, no. 12, pp. 1889–1903, 2007.
[15]
P. Lavenex and D. G. Amaral, “Hippocampal-neocortical interaction: a hierarchy of associativity,” Hippocampus, vol. 10, no. 4, pp. 420–430, 2000.
[16]
B. C. Dickerson, D. H. Salat, J. F. Bates et al., “Medial temporal lobe function and structure in mild cognitive impairment,” Annals of Neurology, vol. 56, no. 1, pp. 27–35, 2004.
[17]
B. C. Dickerson, D. H. Salat, D. N. Greve et al., “Increased hippocampal activation in mild cognitive impairment compared to normal aging and AD,” Neurology, vol. 65, no. 3, pp. 404–411, 2005.
[18]
J. Pariente, S. Cole, R. Henson et al., “Alzheimer's patients engage an alternative network during a memory task,” Annals of Neurology, vol. 58, no. 6, pp. 870–879, 2005.
[19]
M. M. Machulda, H. A. Ward, B. Borowski et al., “Comparison of memory fMRI response among normal, MCI, and Alzheimer's patients,” Neurology, vol. 61, no. 4, pp. 500–506, 2003.
[20]
V. Jelic, S. E. Johansson, O. Almkvist et al., “Quantitative electroencephalography in mild cognitive impairment: longitudinal changes and possible prediction of Alzheimer's disease,” Neurobiology of Aging, vol. 21, no. 4, pp. 533–540, 2000.
[21]
V. Jelic, P. Julin, M. Shigeta et al., “Apolipoprotein E ε4 allele decreases functional connectivity in Alzheimer's disease as measured by EEG coherence,” Journal of Neurology Neurosurgery and Psychiatry, vol. 63, no. 1, pp. 59–65, 1997.
[22]
F. Ferreri, F. Pauri, P. Pasqualetti, R. Fini, G. Dal Forno, and P. M. Rossini, “Motor cortex excitability in Alzheimer's disease: a transcranial magnetic stimulation study,” Annals of Neurology, vol. 53, no. 1, pp. 102–108, 2003.
[23]
Y. A. L. Pijnenburg, Y. Vd Made, A. M. Van Cappellen Van Walsum, D. L. Knol, P. Scheltens, and C. J. Stam, “EEG synchronization likelihood in mild cognitive impairment and Alzheimer's disease during a working memory task,” Clinical Neurophysiology, vol. 115, no. 6, pp. 1332–1339, 2004.
[24]
Z. Y. Jiang, “Study on EEG power and coherence in patients with mild cognitive impairment during working memory task,” Journal of Zhejiang University. Science. B, vol. 6, no. 12, pp. 1213–1219, 2005.
[25]
Z. Y. Jiang and L. L. Zheng, “Inter- and intra-hemispheric EEG coherence in patients with mild cognitive impairment at rest and during working memory task,” Journal of Zhejiang University. Science. B, vol. 7, no. 5, pp. 357–364, 2006.
[26]
L. L. Zheng, Z. Y. Jiang, and E. Y. Yu, “Alpha spectral power and coherence in the patients with mild cognitive impairment during a three-level working memory task,” Journal of Zhejiang University. Science B, vol. 8, no. 8, pp. 584–592, 2007.
[27]
R. Zappoli, A. Versari, M. Paganini et al., “Brain electrical activity (quantitative EEG and bit-mapping neurocognitive CNV components), psychometrics and clinical findings in presenile subjects with initial mild cognitive decline or probable Alzheimer-type dementia,” Italian Journal of Neurological Sciences, vol. 16, no. 6, pp. 341–376, 1995.
[28]
C. Huang, L. O. Wahlund, T. Dierks, P. Julin, B. Winblad, and V. Jelic, “Discrimination of Alzheimer's disease and mild cognitive impairment by equivalent EEG sources: a cross-sectional and longitudinal study,” Clinical Neurophysiology, vol. 111, no. 11, pp. 1961–1967, 2000.
[29]
T. Koenig, L. Prichep, T. Dierks et al., “Decreased EEG synchronization in Alzheimer's disease and mild cognitive impairment,” Neurobiology of Aging, vol. 26, no. 2, pp. 165–171, 2005.
[30]
C. Babiloni, G. Binetti, E. Cassetta et al., “Sources of cortical rhythms change as a function of cognitive impairment in pathological aging: a multicenter study,” Clinical Neurophysiology, vol. 117, no. 2, pp. 252–268, 2006.
[31]
E. J. Golob, R. Irimajiri, and A. Starr, “Auditory cortical activity in amnestic mild cognitive impairment: relationship to subtype and conversion to dementia,” Brain, vol. 130, no. 3, pp. 740–752, 2007.
[32]
D. V. Moretti, C. Miniussi, G. B. Frisoni et al., “Hippocampal atrophy and EEG markers in subjects with mild cognitive impairment,” Clinical Neurophysiology, vol. 118, no. 12, pp. 2716–2729, 2007.
[33]
D. V. Moretti, M. Pievani, C. Fracassi et al., “Increase of theta/Gamma and Alpha3/Alpha2 ratio is associated with amygdalo-hippocampal complex atrophy,” Journal of Alzheimer's Disease, vol. 17, no. 2, pp. 349–357, 2009.
[34]
D. V. Moretti, C. Fracassi, M. Pievani et al., “Increase of theta/gamma ratio is associated with memory impairment,” Clinical Neurophysiology, vol. 120, no. 2, pp. 295–303, 2009.
[35]
D. V. Moretti, C. Miniussi, G. Frisoni et al., “Vascular damage and EEG markers in subjects with mild cognitive impairment,” Clinical Neurophysiology, vol. 118, no. 8, pp. 1866–1876, 2007.
[36]
J. H. Kramer, B. R. Reed, D. Mungas, M. W. Weiner, and H. C. Chui, “Executive dysfunction in subcortical ischaemic vascular disease,” Journal of Neurology Neurosurgery and Psychiatry, vol. 72, no. 2, pp. 217–220, 2002.
[37]
D. V. Moretti, C. Babiloni, G. Binetti et al., “Individual analysis of EEG frequency and band power in mild Alzheimer's disease,” Clinical Neurophysiology, vol. 115, no. 2, pp. 299–308, 2004.
[38]
W. Klimesch, “EEG alpha and theta oscillations reflect cognitive and memory performance: a review and analysis,” Brain Research Reviews, vol. 29, no. 2-3, pp. 169–195, 1999.
[39]
M. F. Folstein, S. E. Folstein, and P. R. McHugh, ““Mini mental state”. A practical method for grading the cognitive state of patients for the clinician,” Journal of Psychiatric Research, vol. 12, no. 3, pp. 189–198, 1975.
[40]
C. P. Hughes, L. Berg, and W. L. Danziger, “A new clinical scale for the staging of dementia,” British Journal of Psychiatry, vol. 140, no. 6, pp. 566–572, 1982.
[41]
W. G. Rosen, R. D. Terry, and P. A. Fuld, “Pathological verification of ischemic score in differentiation of dementias,” Annals of Neurology, vol. 7, no. 5, pp. 486–488, 1980.
[42]
M. P. Lawton and E. M. Brody, “Assessment of older people: self-maintaining and instrumental activities of daily living,” Gerontologist, vol. 9, no. 3, pp. 179–186, 1969.
[43]
M. Albert, L. A. Smith, P. A. Scherr, J. O. Taylor, D. A. Evans, and H. H. Funkenstein, “Use of brief cognitive tests to identify individuals in the community with clinically diagnosed Alzheimer's disease,” International Journal of Neuroscience, vol. 57, no. 3-4, pp. 167–178, 1991.
[44]
R. C. Petersen, G. E. Smith, S. C. Waring, R. J. Ivnik, E. Kokmen, and E. G. Tangelos, “Aging, memory, and mild cognitive impairment,” International Psychogeriatrics, vol. 9, no. 1, supplement, pp. 65–69, 1997.
[45]
F. Portet, P. J. Ousset, P. J. Visser et al., “Mild cognitive impairment (MCI) in medical practice: a critical review of the concept and new diagnostic procedure. Report of the MCI Working Group of the European Consortium on Alzheimer's Disease,” Journal of Neurology, Neurosurgery and Psychiatry, vol. 77, no. 6, pp. 714–718, 2006.
[46]
C. Geroldi, R. Rossi, C. Calvagna et al., “Medial temporal atrophy but not memory deficit predicts progression to dementia in patients with mild cognitive impairment,” Journal of Neurology, Neurosurgery and Psychiatry, vol. 77, no. 11, pp. 1219–1222, 2006.
[47]
K. I. Shulman, “Clock-drawing: is it the ideal cognitive screening test?” International Journal of Geriatric Psychiatry, vol. 15, no. 6, pp. 548–561, 2000.
[48]
P. Amodio, H. Wenin, F. Del Piccolo et al., “Variability of trail making test, symbol digit test and line trait test in normal people. A normative study taking into account age-dependent decline and sociobiological variables,” Aging, vol. 14, no. 2, pp. 117–131, 2002.
[49]
A. Basso, E. Capitani, and M. Laiacona, “Raven's coloured progressive matrices: normative values on 305 adult normal controls,” Functional Neurology, vol. 2, no. 2, pp. 189–194, 1987.
[50]
H. Spinnler and G. Tognoni, “Italian standardization and classification of neuropsychological tests,” Italian Journal of Neurological Sciences, vol. 6, supplement 8, pp. 1–120, 1987.
[51]
G. A. Carlesimo, C. Caltagirone, and G. Gainotti, “The mental deterioration battery: normative data, diagnostic reliability and qualitative analyses of cognitive impairment,” European Neurology, vol. 36, no. 6, pp. 378–384, 1996.
[52]
P. Caffarra, G. Vezzadini, F. Dieci, F. Zonato, and A. Venneri, “Rey-Osterrieth complex figure: normative values in an Italian population sample,” Neurological Sciences, vol. 22, no. 6, pp. 443–447, 2002.
[53]
L. S. Radloff, “The CES-D scale: a self-report depression scale for research in the general population,” Applied Psychological Measurement, vol. 1, pp. 385–401, 1977.
[54]
L. O. Wahlund, F. Barkhof, F. Fazekas, et al., “A new rating scale for age-related white matter changes applicable to MRI and CT,” Stroke, vol. 32, no. 6, pp. 1318–1322, 2001.
[55]
C. J. Stam, Y. Van Der Made, Y. A. L. Pijnenburg, and P. Scheltens, “EEG synchronization in mild cognitive impairment and Alzheimer's disease,” Acta Neurologica Scandinavica, vol. 108, no. 2, pp. 90–96, 2003.
[56]
T. Seidenbecher, T. R. Laxmi, O. Stork, and H. C. Pape, “Amygdalar and hippocampal theta rhythm synchronization during fear memory retrieval,” Science, vol. 301, no. 5634, pp. 846–850, 2003.
[57]
R. T. Narayanan, T. Seidenbecher, S. Sangha, O. Stork, and H. C. Pape, “Theta resynchronization during reconsolidation of remote contextual fear memory,” NeuroReport, vol. 18, no. 11, pp. 1107–1111, 2007.
[58]
S. M. Montgomery and G. Buzsáki, “Gamma oscillations dynamically couple hippocampal CA3 and CA1 regions during memory task performance,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 36, pp. 14495–14500, 2007.
[59]
P. Sauseng, W. Klimesch, M. Doppelmayr, S. Hanslmayr, M. Schabus, and W. R. Gruber, “Theta coupling in the human electroencephalogram during a working memory task,” Neuroscience Letters, vol. 354, no. 2, pp. 123–126, 2004.
[60]
A. Bragin, G. Jando, Z. Nadasdy, J. Hetke, K. Wise, and G. Buzsaki, “Gamma (40–100 Hz) oscillation in the hippocampus of the behaving rat,” Journal of Neuroscience, vol. 15, no. 1 I, pp. 47–60, 1995.
[61]
R. R. Llinás, U. Ribary, D. Jeanmonod, E. Kronberg, and P. P. Mitra, “Thalamocortical dysrhythmia: a neurological and neuropsychiatric syndrome characterized by magnetoencephalography,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 26, pp. 15222–15227, 1999.
[62]
W. Klimesch, P. Sauseng, and S. Hanslmayr, “EEG alpha oscillations: the inhibition-timing hypothesis,” Brain Research Reviews, vol. 53, no. 1, pp. 63–88, 2007.
[63]
D. Paré, D. R. Collins, and J. G. Pelletier, “Amygdala oscillations and the consolidation of emotional memories,” Trends in Cognitive Sciences, vol. 6, no. 7, pp. 306–314, 2002.
[64]
M. Garolera, R. Coppola, K. E. Mu？oz et al., “Amygdala activation in affective priming: a magnetoencephalogram study,” NeuroReport, vol. 18, no. 14, pp. 1449–1453, 2007.
[65]
K. A. Young, L. A. Holcomb, W. L. Bonkale, P. B. Hicks, U. Yazdani, and D. C. German, “5HTTLPR polymorphism and enlargement of the pulvinar: unlocking the backdoor to the limbic system,” Biological Psychiatry, vol. 61, no. 6, pp. 813–818, 2007.
[66]
J. M. Ellison, D. G. Harper, Y. Berlow, and L. Zeranski, “Beyond the “C” in MCI: noncognitive symptoms in amnestic and non-amnestic mild cognitive impairment,” CNS Spectrums, vol. 13, no. 1, pp. 66–72, 2008.
[67]
L. Rozzini, B. Vicini Chilovi, M. Conti et al., “Neuropsychiatric symptoms in amnestic and nonamnestic mild cognitive impairment,” Dementia and Geriatric Cognitive Disorders, vol. 25, no. 1, pp. 32–36, 2007.
[68]
P. Johannsen, J. Jakobsen, P. Bruhn, and A. Gjedde, “Cortical responses to sustained and divided attention in Alzheimer's disease,” NeuroImage, vol. 10, no. 3, pp. 269–281, 1999.
[69]
A. M. Berardi, R. Parasuraman, and J. V. Haxby, “Sustained attention in mild Alzheimer's disease,” Developmental Neuropsychology, vol. 28, no. 1, pp. 507–537, 2005.
[70]
E. J. Levinoff, D. Saumier, and H. Chertkow, “Focused attention deficits in patients with Alzheimer's disease and mild cognitive impairment,” Brain and Cognition, vol. 57, no. 2, pp. 127–130, 2005.
[71]
A. Tales, J. Haworth, S. Nelson, R. J. Snowden, and G. Wilcock, “Abnormal visual search in mild cognitive impairment and Alzheimer's disease,” Neurocase, vol. 11, no. 1, pp. 80–84, 2005.
[72]
A. Tales, R. J. Snowden, J. Haworth, and G. Wilcock, “Abnormal spatial and non-spatial cueing effects in mild cognitive impairment and Alzheimer's disease,” Neurocase, vol. 11, no. 1, pp. 85–92, 2005.
[73]
O. C. Zalay and B. L. Bardakjian, “Simulated mossy fiber associated feedforward circuit functioning as a highpass filter,” in Proceedings of the 28th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBS '06), pp. 4979–4982, September 2006.
[74]
G. B. Frisoni, S. Galluzzi, L. Bresciani, O. Zanetti, and C. Geroldi, “Mild cognitive impairment with subcortical vascular features: clinical characteristics and outcome,” Journal of Neurology, vol. 249, no. 10, pp. 1423–1432, 2002.
[75]
S. Galluzzi, C. F. Sheu, O. Zanetti, and G. B. Frisoni, “Distinctive clinical features of mild cognitive impairment with subcortical cerebrovascular disease,” Dementia and Geriatric Cognitive Disorders, vol. 19, no. 4, pp. 196–203, 2005.
[76]
M. Steriade and R. R. Llinas, “The functional states of the thalamus and the associated neuronal interplay,” Physiological Reviews, vol. 68, no. 3, pp. 649–742, 1988.
[77]
F. H. Lopes da Silva, A. van Rotterdam, P. Barts, E. van Heusden, and W. Burr, “Models of neuronal populations: the basic mechanisms of rhythmicity,” Progress in Brain Research, vol. 45, no. C, pp. 281–308, 1976.
[78]
P. L. Nunez, B. M. Wingeier, and R. B. Silberstein, “Spatial-temporal structures of human alpha rhythms: theory, microcurrent sources, multiscale measurements, and global binding of local networks,” Human Brain Mapping, vol. 13, no. 3, pp. 125–164, 2001.
[79]
B. Doiron, M. J. Chacron, L. Maler, A. Longtin, and J. Bastian, “Inhibitory feedback required for network oscillatory responses to communication but not prey stimuli,” Nature, vol. 421, no. 6922, pp. 539–543, 2003.
[80]
P. L. Nunez and R. Srinivasan, “A theoretical basis for standing and traveling brain waves measured with human EEG with implications for an integrated consciousness,” Clinical Neurophysiology, vol. 117, no. 11, pp. 2424–2435, 2006.
[81]
B. Szelies, R. Mielke, J. Kessler, and W. D. Heiss, “EEG power changes are related to regional cerebral glucose metabolism in vascular dementia,” Clinical Neurophysiology, vol. 110, no. 4, pp. 615–620, 1999.
[82]
L. Leocani, T. Locatelli, V. Martinelli et al., “Electroencephalographic coherence analysis in multiple sclerosis: correlation with clinical, neuropsychological, and MRI findings,” Journal of Neurology Neurosurgery and Psychiatry, vol. 69, no. 2, pp. 192–198, 2000.
[83]
E. S. Goldensohn, “Use of EEG for evaluation of focal intracranial lesions,” in Current Practice of Clinical Electroencephalography, D. W. Klass and D. D. Daly, Eds., pp. 307–341, Raven, New York, NY, USA, 1979.
