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Joint effects of gray matter atrophy and altered functional connectivity on cognitive deficits in amnestic mild cognitive impairment patients

Published online by Cambridge University Press:  16 December 2014

C. Xie*
Affiliation:
Department of Neurology, Affiliated Zhongda Hospital of Southeast University, Nanjing, People's Republic of China Institute of Neuropsychiatry of Southeast University, Nanjing, People's Republic of China
F. Bai
Affiliation:
Department of Neurology, Affiliated Zhongda Hospital of Southeast University, Nanjing, People's Republic of China Institute of Neuropsychiatry of Southeast University, Nanjing, People's Republic of China
B. Yuan
Affiliation:
Department of Neurology, Affiliated Zhongda Hospital of Southeast University, Nanjing, People's Republic of China Institute of Neuropsychiatry of Southeast University, Nanjing, People's Republic of China
H. Yu
Affiliation:
Department of Neurology, Affiliated Zhongda Hospital of Southeast University, Nanjing, People's Republic of China
Y. Shi
Affiliation:
Institute of Neuropsychiatry of Southeast University, Nanjing, People's Republic of China
Y. Yuan
Affiliation:
Department of Psychology, Affiliated Zhongda Hospital of Southeast University, Nanjing, People's Republic of China
D. Wu
Affiliation:
Department of Neurology, Affiliated Zhongda Hospital of Southeast University, Nanjing, People's Republic of China
Z.-S. Zhang
Affiliation:
Department of Neurology, Affiliated Zhongda Hospital of Southeast University, Nanjing, People's Republic of China Institute of Neuropsychiatry of Southeast University, Nanjing, People's Republic of China
Z.-J. Zhang*
Affiliation:
Department of Neurology, Affiliated Zhongda Hospital of Southeast University, Nanjing, People's Republic of China Institute of Neuropsychiatry of Southeast University, Nanjing, People's Republic of China
*
*Address for correspondence: C. Xie, Ph.D., M.D., Department of Neurology, Affiliated Zhongda Hospital of Southeast University, no. 87 DingJiaQiao Road, Nanjing 210009, People's Republic of China. (Email: [email protected]) [C.X.] (Email: [email protected]) [Z.-J.Z.]
*Address for correspondence: C. Xie, Ph.D., M.D., Department of Neurology, Affiliated Zhongda Hospital of Southeast University, no. 87 DingJiaQiao Road, Nanjing 210009, People's Republic of China. (Email: [email protected]) [C.X.] (Email: [email protected]) [Z.-J.Z.]

Abstract

Background

Gray matter (GM) atrophy and disrupted intrinsic functional connectivity (IFC) are often present in patients with amnestic mild cognitive impairment (aMCI), which shows high risk of developing into Alzheimer's disease. Little is known, however, about the relationship between GM atrophy and altered IFC, and whether they are related to cognitive decline.

Method

A total of 30 aMCI and 26 cognitively normal (CN) subjects were recruited for this study. Optimized voxel-based morphometric and resting-state functional connectivity magnetic resonance imaging approaches were performed to measure the GM volumes (GMVs) and atrophy-related IFC, respectively. Multivariate linear regression analysis was used to examine the effects of GM atrophy and IFC on cognitive performance across subjects, after controlling for the effects of age, education, gender and group.

Results

Compared with CN subjects, aMCI subjects showed significantly reduced GMVs and decreased IFC in the frontal-parietal and medial temporal lobe systems. Multivariate regression analysis further demonstrated that the GMVs and decreased IFC simultaneously affected the cognitive function. Specifically, GMVs were positively correlated with cognitive performances, including global cognition and episodic memory, and showed a strong trend in correlation between GMVs and non-episodic memory, whilst IFC was positively correlated with the above three cognitive measures, across all subjects. In addition, significant correlation was found between GMVs and altered IFC strength across all subjects.

Conclusions

Our findings demonstrated that GMVs and IFC jointly contribute to cognitive performance, and combining quantitative information about GMVs and the strength of functional connectivity may serve as an indicator of cognitive deficits in non-demented elderly.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2014 

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References

Agosta, F, Rocca, MA, Pagani, E, Absinta, M, Magnani, G, Marcone, A, Falautano, M, Comi, G, Gorno-Tempini, ML, Filippi, M (2010). Sensorimotor network rewiring in mild cognitive impairment and Alzheimer's disease. Human Brain Mapping 31, 515525.CrossRefGoogle ScholarPubMed
Andrews-Hanna, JR, Snyder, AZ, Vincent, JL, Lustig, C, Head, D, Raichle, ME, Buckner, RL (2007). Disruption of large-scale brain systems in advanced aging. Neuron 56, 924935.CrossRefGoogle ScholarPubMed
Bai, F, Watson, DR, Yu, H, Shi, Y, Yuan, Y, Zhang, Z (2009a). Abnormal resting-state functional connectivity of posterior cingulate cortex in amnestic type mild cognitive impairment. Brain Research 1302, 167174.CrossRefGoogle ScholarPubMed
Bai, F, Zhang, Z, Watson, DR, Yu, H, Shi, Y, Yuan, Y, Zang, Y, Zhu, C, Qian, Y (2009b). Abnormal functional connectivity of hippocampus during episodic memory retrieval processing network in amnestic mild cognitive impairment. Biological Psychiatry 65, 951958.CrossRefGoogle ScholarPubMed
Balthazar, ML, Yasuda, CL, Cendes, F, Damasceno, BP (2010). Learning, retrieval, and recognition are compromised in aMCI and mild AD: are distinct episodic memory processes mediated by the same anatomical structures? Journal of the International Neuropsychological Society 16, 205209.CrossRefGoogle ScholarPubMed
Balthazar, ML, Yasuda, CL, Pereira, FR, Pedro, T, Damasceno, BP, Cendes, F (2009). Differences in grey and white matter atrophy in amnestic mild cognitive impairment and mild Alzheimer's disease. European Journal of Neurology 16, 468474.CrossRefGoogle ScholarPubMed
Bell-McGinty, S, Lopez, OL, Meltzer, CC, Scanlon, JM, Whyte, EM, Dekosky, ST, Becker, JT (2005). Differential cortical atrophy in subgroups of mild cognitive impairment. Archives of Neurology 62, 13931397.CrossRefGoogle ScholarPubMed
Bourgeat, P, Chetelat, G, Villemagne, VL, Fripp, J, Raniga, P, Pike, K, Acosta, O, Szoeke, C, Ourselin, S, Ames, D, Ellis, KA, Martins, RN, Masters, CL, Rowe, CC, Salvado, O (2010). β-Amyloid burden in the temporal neocortex is related to hippocampal atrophy in elderly subjects without dementia. Neurology 74, 121127.CrossRefGoogle ScholarPubMed
Brambati, SM, Belleville, S, Kergoat, MJ, Chayer, C, Gauthier, S, Joubert, S (2009). Single- and multiple-domain amnestic mild cognitive impairment: two sides of the same coin? Dementia and Geriatric Cognitive Disorders 28, 541549.CrossRefGoogle ScholarPubMed
Buckner, RL, Sepulcre, J, Talukdar, T, Krienen, FM, Liu, H, Hedden, T, Andrews-Hanna, JR, Sperling, RA, Johnson, KA (2009). Cortical hubs revealed by intrinsic functional connectivity: mapping, assessment of stability, and relation to Alzheimer's disease. Journal of Neuroscience 29, 18601873.CrossRefGoogle ScholarPubMed
Buckner, RL, Snyder, AZ, Shannon, BJ, LaRossa, G, Sachs, R, Fotenos, AF, Sheline, YI, Klunk, WE, Mathis, CA, Morris, JC, Mintun, MA (2005). Molecular, structural, and functional characterization of Alzheimer's disease: evidence for a relationship between default activity, amyloid, and memory. Journal of Neuroscience 25, 77097717.CrossRefGoogle ScholarPubMed
Bullmore, E, Sporns, O (2009). Complex brain networks: graph theoretical analysis of structural and functional systems. Nature Reviews Neuroscience 10, 186198.CrossRefGoogle ScholarPubMed
Cavanna, AE (2006). The precuneus: a review of its functional anatomy and behavioural correlates. Brain 129, 564583.CrossRefGoogle ScholarPubMed
Chen, G, Chen, G, Xie, C, Ward, BD, Li, W, Antuono, P, Li, SJ (2012). A method to determine the necessity for global signal regression in resting-state fMRI studies. Magnetic Resonance in Medicine 68, 18281835.CrossRefGoogle ScholarPubMed
Delbeuck, X, Collette, F, Van der Linden, A (2007). Is Alzheimer's disease a disconnection syndrome? Evidence from a crossmodal audio-visual illusory experiment. Neuropsychologia 45, 33153323.CrossRefGoogle ScholarPubMed
Dickerson, BC, Salat, DH, Greve, DN, Chua, EF, Rand-Giovannetti, E, Rentz, DM, Bertram, L, Mullin, K, Tanzi, RE, Blacker, D, Albert, MS, Sperling, RA (2005). Increased hippocampal activation in mild cognitive impairment compared to normal aging and AD. Neurology 65, 404411.CrossRefGoogle ScholarPubMed
Dorfel, D, Werner, A, Schaefer, M, von Kummer, R, Karl, A (2009). Distinct brain networks in recognition memory share a defined region in the precuneus. European Journal of Neuroscience 30, 19471959.CrossRefGoogle Scholar
Dosenbach, NU, Fair, DA, Miezin, FM, Cohen, AL, Wenger, KK, Dosenbach, RA, Fox, MD, Snyder, AZ, Vincent, JL, Raichle, ME, Schlaggar, BL, Petersen, SE (2007). Distinct brain networks for adaptive and stable task control in humans. Proceedings of the National Academy of Sciences of the United States of America 104, 1107311078.CrossRefGoogle ScholarPubMed
Duyn, JH, Moonen, CT (1993). Fast proton spectroscopic imaging of human brain using multiple spin-echoes. Magnetic Resonance in Medicine 30, 409414.CrossRefGoogle ScholarPubMed
Ersche, KD, Jones, PS, Williams, GB, Turton, AJ, Robbins, TW, Bullmore, ET (2012). Abnormal brain structure implicated in stimulant drug addiction. Science 335, 601604.CrossRefGoogle ScholarPubMed
Ferreira, LK, Diniz, BS, Forlenza, OV, Busatto, GF, Zanetti, MV (2011). Neurostructural predictors of Alzheimer's disease: a meta-analysis of VBM studies. Neurobiology of Aging 32, 17331741.CrossRefGoogle ScholarPubMed
Fox, MD, Raichle, ME (2007). Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nature Reviews Neuroscience 8, 700711.CrossRefGoogle ScholarPubMed
Gauthier, S, Reisberg, B, Zaudig, M, Petersen, RC, Ritchie, K, Broich, K, Belleville, S, Brodaty, H, Bennett, D, Chertkow, H, Cummings, JL, de Leon, M, Feldman, H, Ganguli, M, Hampel, H, Scheltens, P, Tierney, MC, Whitehouse, P, Winblad, B (2006). Mild cognitive impairment. Lancet 367, 12621270.CrossRefGoogle ScholarPubMed
Gili, T, Cercignani, M, Serra, L, Perri, R, Giove, F, Maraviglia, B, Caltagirone, C, Bozzali, M (2011). Regional brain atrophy and functional disconnection across Alzheimer's disease evolution. Journal of Neurology, Neurosurgery and Psychiatry 82, 5866.CrossRefGoogle ScholarPubMed
Greicius, MD, Srivastava, G, Reiss, AL, Menon, V (2004). Default-mode network activity distinguishes Alzheimer's disease from healthy aging: evidence from functional MRI. Proceedings of the National Academy of Sciences of the United States of America 101, 46374642.CrossRefGoogle ScholarPubMed
Hagmann, P, Cammoun, L, Gigandet, X, Meuli, R, Honey, CJ, Wedeen, VJ, Sporns, O (2008). Mapping the structural core of human cerebral cortex. PLoS Biology 6, e159.CrossRefGoogle ScholarPubMed
Hamalainen, A, Tervo, S, Grau-Olivares, M, Niskanen, E, Pennanen, C, Huuskonen, J, Kivipelto, M, Hanninen, T, Tapiola, M, Vanhanen, M, Hallikainen, M, Helkala, EL, Nissinen, A, Vanninen, R, Soininen, H (2007). Voxel-based morphometry to detect brain atrophy in progressive mild cognitive impairment. NeuroImage 37, 11221131.CrossRefGoogle ScholarPubMed
Joubert, S, Brambati, SM, Ansado, J, Barbeau, EJ, Felician, O, Didic, M, Lacombe, J, Goldstein, R, Chayer, C, Kergoat, MJ (2010). The cognitive and neural expression of semantic memory impairment in mild cognitive impairment and early Alzheimer's disease. Neuropsychologia 48, 978988.CrossRefGoogle ScholarPubMed
Karas, G, Sluimer, J, Goekoop, R, van der Flier, W, Rombouts, SA, Vrenken, H, Scheltens, P, Fox, N, Barkhof, F (2008). Amnestic mild cognitive impairment: structural MR imaging findings predictive of conversion to Alzheimer disease. American Journal of Neuroradiology 29, 944949.CrossRefGoogle ScholarPubMed
Karas, GB, Scheltens, P, Rombouts, SA, Visser, PJ, van Schijndel, RA, Fox, NC, Barkhof, F (2004). Global and local gray matter loss in mild cognitive impairment and Alzheimer's disease. NeuroImage 23, 708716.CrossRefGoogle ScholarPubMed
Kong, L, Chen, K, Tang, Y, Wu, F, Driesen, N, Womer, F, Fan, G, Ren, L, Jiang, W, Cao, Y, Blumberg, HP, Xu, K, Wang, F (2013). Functional connectivity between the amygdala and prefrontal cortex in medication-naive individuals with major depressive disorder. Journal of Psychiatry and Neuroscience 38, 417422.CrossRefGoogle ScholarPubMed
Laird, AR, Eickhoff, SB, Li, K, Robin, DA, Glahn, DC, Fox, PT (2009). Investigating the functional heterogeneity of the default mode network using coordinate-based meta-analytic modeling. Journal of Neuroscience 29, 1449614505.CrossRefGoogle ScholarPubMed
Liu, H, Qin, W, Li, W, Fan, L, Wang, J, Jiang, T, Yu, C (2013). Connectivity-based parcellation of the human frontal pole with diffusion tensor imaging. Journal of Neuroscience 33, 67826790.CrossRefGoogle ScholarPubMed
Lui, S, Deng, W, Huang, X, Jiang, L, Ma, X, Chen, H, Zhang, T, Li, X, Li, D, Zou, L, Tang, H, Zhou, XJ, Mechelli, A, Collier, DA, Sweeney, JA, Li, T, Gong, Q (2009). Association of cerebral deficits with clinical symptoms in antipsychotic-naive first-episode schizophrenia: an optimized voxel-based morphometry and resting state functional connectivity study. American Journal of Psychiatry 166, 196205.CrossRefGoogle ScholarPubMed
Machulda, MM, Senjem, ML, Weigand, SD, Smith, GE, Ivnik, RJ, Boeve, BF, Knopman, DS, Petersen, RC, Jack, CR (2009). Functional magnetic resonance imaging changes in amnestic and nonamnestic mild cognitive impairment during encoding and recognition tasks. Journal of the International Neuropsychological Society 15, 372382.CrossRefGoogle ScholarPubMed
Markesbery, WR (2010). Neuropathologic alterations in mild cognitive impairment: a review. Journal of Alzheimer's Disease 19, 221228.CrossRefGoogle ScholarPubMed
Mason, MF, Norton, MI, Van Horn, JD, Wegner, DM, Grafton, ST, Macrae, CN (2007). Wandering minds: the default network and stimulus-independent thought. Science 315, 393395.CrossRefGoogle ScholarPubMed
Mesulam, M (2009). Defining neurocognitive networks in the BOLD new world of computed connectivity. Neuron 62, 13.CrossRefGoogle ScholarPubMed
Miller, SL, Fenstermacher, E, Bates, J, Blacker, D, Sperling, RA, Dickerson, BC (2008). Hippocampal activation in adults with mild cognitive impairment predicts subsequent cognitive decline. Journal of Neurology, Neurosurgery and Psychiatry 79, 630635.CrossRefGoogle ScholarPubMed
Morbelli, S, Piccardo, A, Villavecchia, G, Dessi, B, Brugnolo, A, Piccini, A, Caroli, A, Frisoni, G, Rodriguez, G, Nobili, F (2010). Mapping brain morphological and functional conversion patterns in amnestic MCI: a voxel-based MRI and FDG-PET study. European Journal of Nuclear Medicine and Molecular Imaging 37, 3645.CrossRefGoogle ScholarPubMed
Palop, JJ, Chin, J, Mucke, L (2006). A network dysfunction perspective on neurodegenerative diseases. Nature 443, 768773.CrossRefGoogle ScholarPubMed
Pessoa, L (2008). On the relationship between emotion and cognition. Nature Reviews Neuroscience 9, 148158.CrossRefGoogle ScholarPubMed
Petersen, RC (2004). Mild cognitive impairment as a diagnostic entity. Journal of Internal Medicine 256, 183194.CrossRefGoogle ScholarPubMed
Petersen, RC, Smith, GE, Waring, SC, Ivnik, RJ, Tangalos, EG, Kokmen, E (1999). Mild cognitive impairment: clinical characterization and outcome. Archives of Neurology 56, 303308.CrossRefGoogle ScholarPubMed
Qi, Z, Wu, X, Wang, Z, Zhang, N, Dong, H, Yao, L, Li, K (2010). Impairment and compensation coexist in amnestic MCI default mode network. NeuroImage 50, 4855.CrossRefGoogle ScholarPubMed
Ringman, JM, Diaz-Olavarrieta, C, Rodriguez, Y, Chavez, M, Fairbanks, L, Paz, F, Varpetian, A, Maldonado, HC, Macias-Islas, MA, Murrell, J, Ghetti, B, Kawas, C (2005). Neuropsychological function in nondemented carriers of presenilin-1 mutations. Neurology 65, 552558.CrossRefGoogle ScholarPubMed
Rombouts, SARB, Barkhof, F, Goekoop, R, Stam, CJ, Scheltens, P (2005). Altered resting state networks in mild cognitive impairment and mild Alzheimer's disease: an fMRI study. Human Brain Mapping 26, 231239.CrossRefGoogle ScholarPubMed
Schmidt-Wilcke, T, Poljansky, S, Hierlmeier, S, Hausner, J, Ibach, B (2009). Memory performance correlates with gray matter density in the ento-/perirhinal cortex and posterior hippocampus in patients with mild cognitive impairment and healthy controls – a voxel based morphometry study. NeuroImage 47, 19141920.CrossRefGoogle ScholarPubMed
Schneider, JA, Boyle, PA, Arvanitakis, Z, Bienias, JL, Bennett, DA (2007). Subcortical infarcts, Alzheimer's disease pathology, and memory function in older persons. Annals of Neurology 62, 5966.CrossRefGoogle ScholarPubMed
Seeley, WW, Crawford, RK, Zhou, J, Miller, BL, Greicius, MD (2009). Neurodegenerative diseases target large-scale human brain networks. Neuron 62, 4252.CrossRefGoogle ScholarPubMed
Serra, L, Giulietti, G, Cercignani, M, Spano, B, Torso, M, Castelli, D, Perri, R, Fadda, L, Marra, C, Caltagirone, C, Bozzali, M (2013). Mild cognitive impairment: same identity for different entities. Journal of Alzheimer's Disease 33, 11571165.CrossRefGoogle ScholarPubMed
Smith, CD (2010). Neuroimaging through the course of Alzheimer's disease. Journal of Alzheimer's Disease 19, 273290.CrossRefGoogle ScholarPubMed
Smith, CD (2012). Structural imaging in early pre-states of dementia. Biochimica et Biophysica Acta 1822, 317324.CrossRefGoogle ScholarPubMed
Sorg, C, Riedl, V, Muhlau, M, Calhoun, VD, Eichele, T, Laer, L, Drzezga, A, Forstl, H, Kurz, A, Zimmer, C, Wohlschlager, AM (2007). Selective changes of resting-state networks in individuals at risk for Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America 104, 1876018765.CrossRefGoogle ScholarPubMed
Sporns, O, Honey, CJ, Kotter, R (2007). Identification and classification of hubs in brain networks. PLoS ONE 2, e1049.CrossRefGoogle ScholarPubMed
Spulber, G, Niskanen, E, Macdonald, S, Kivipelto, M, Padilla, DF, Julkunen, V, Hallikainen, M, Vanninen, R, Wahlund, LO, Soininen, H (2012). Evolution of global and local grey matter atrophy on serial MRI scans during the progression from MCI to AD. Current Alzheimer Research 9, 516524.CrossRefGoogle ScholarPubMed
Venneri, A, Gorgoglione, G, Toraci, C, Nocetti, L, Panzetti, P, Nichelli, P (2011). Combining neuropsychological and structural neuroimaging indicators of conversion to Alzheimer's disease in amnestic mild cognitive impairment. Current Alzheimer Research 8, 789797.CrossRefGoogle ScholarPubMed
Wang, L, LaViolette, P, O'Keefe, K, Putcha, D, Bakkour, A, Van Dijk, KRA, Pihlajamäki, M, Dickerson, BC, Sperling, RA (2010). Intrinsic connectivity between the hippocampus and posteromedial cortex predicts memory performance in cognitively intact older individuals. NeuroImage 51, 910917.CrossRefGoogle ScholarPubMed
Whitwell, JL, Petersen, RC, Negash, S, Weigand, SD, Kantarci, K, Ivnik, RJ, Knopman, DS, Boeve, BF, Smith, GE, Jack, CR Jr (2007a). Patterns of atrophy differ among specific subtypes of mild cognitive impairment. Archives of Neurology 64, 11301138.CrossRefGoogle ScholarPubMed
Whitwell, JL, Przybelski, SA, Weigand, SD, Knopman, DS, Boeve, BF, Petersen, RC, Jack, CR Jr (2007b). 3D maps from multiple MRI illustrate changing atrophy patterns as subjects progress from mild cognitive impairment to Alzheimer's disease. Brain 130, 17771786.CrossRefGoogle ScholarPubMed
Wilson, RS, Leurgans, SE, Foroud, TM, Sweet, RA, Graff-Radford, N, Mayeux, R, Bennett, DA (2010). Telephone assessment of cognitive function in the late-onset Alzheimer's disease family study. Archives of Neurology 67, 855861.CrossRefGoogle ScholarPubMed
Xie, C, Bai, F, Yu, H, Shi, Y, Yuan, Y, Chen, G, Li, W, Zhang, Z, Li, SJ (2012). Abnormal insula functional network is associated with episodic memory decline in amnestic mild cognitive impairment. NeuroImage 63, 320327.CrossRefGoogle ScholarPubMed
Xie, C, Li, SJ, Shao, Y, Fu, L, Goveas, J, Ye, E, Li, W, Cohen, AD, Chen, G, Zhang, Z, Yang, Z (2011). Identification of hyperactive intrinsic amygdala network connectivity associated with impulsivity in abstinent heroin addicts. Behavioural Brain Research 216, 639646.CrossRefGoogle ScholarPubMed
Xu, Y, Xu, G, Wu, G, Antuono, P, Rowe, DB, Li, SJ (2008). The phase shift index for marking functional asynchrony in Alzheimer's disease patients using fMRI. Magnetic Resonance Imaging 26, 379392.CrossRefGoogle ScholarPubMed
Yuan, K, Qin, W, Dong, M, Liu, J, Sun, J, Liu, P, Zhang, Y, Wang, W, Wang, Y, Li, Q, Zhao, L, von Deneen, KM, Liu, Y, Gold, MS, Tian, J (2010). Gray matter deficits and resting-state abnormalities in abstinent heroin-dependent individuals. Neuroscience Letters 482, 101105.CrossRefGoogle ScholarPubMed
Zar, J (1996). Biostatistical Analysis, 3rd edn. Prentice-Hall, Inc.: Upper Saddle River, NJ.Google Scholar
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