A network diffusion model of disease progression in dementia
Open accessAbstract
Patterns of dementia are known to fall into dissociated but dispersed brain networks, suggesting that the disease is transmitted along neuronal pathways rather than by proximity. This view is supported by neuropathological evidence for "prion-like" transsynaptic transmission of disease agents like misfolded tau and beta amyloid. We mathematically model this transmission by a diffusive mechanism mediated by the brain's connectivity network obtained from tractography of 14 healthy-brain MRIs. Subsequent graph theoretic analysis provides a fully quantitative, testable, predictive model of dementia. Specifically, we predict spatially distinct "persistent modes," which, we found, recapitulate known patterns of dementia and match recent reports of selectively vulnerable dissociated brain networks. Model predictions also closely match T1-weighted MRI volumetrics of 18 Alzheimer's and 18 frontotemporal dementia subjects. Prevalence rates predicted by the model strongly agree with published data. This work has many important implications, including dimensionality reduction, differential diagnosis, and especially prediction of future atrophy using baseline MRI morphometrics.
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There is post-mortem evidence in AD for regional spread of tau pathology, and more recent neuroimaging studies in human AD suggest epicentres or nodes that may link to network dysfunction.
“There is post-mortem evidence in AD for this regional spread (Zhou Gennatas et al., 2012) and more recent neuroimaging studies in human AD suggest “epicentres” (Zhou et al., 2012) or “nodes” (Raj et al., 2012) that may link to network dysfunction.”
From In vivo imaging of tau pathology using multi-parametric quantitative MRI (2015) · cites this paper as Raj et al., 2012
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Advances in functional and structural MR image analysis and implementation as FSL
Smith, S. M., Jenkinson, M., Woolrich, M. W., Beckmann, C. F., Behrens, T. E. J., Johansen-Berg, H., Bannister, P. R., De Luca, M., Drobnjak, I., Flitney, D. E., et al. (2004) · NeuroImage · doi:10.1016/j.neuroimage.2004.07.051 · Cited by 13,630 · see citing works
Fischl, B., Salat, D. H., Busa, E., Albert, M., Dieterich, M., Haselgrove, C., van der Kouwe, A., Killiany, R., Kennedy, D., Klaveness, S., et al. (2002) · Neuron · doi:10.1016/s0896-6273(02)00569-x · Cited by 8,610 · see citing works
Buckner, R. L., Snyder, A. Z., Shannon, B. J., LaRossa, G., Sachs, R., Fotenos, A. F., Sheline, Y. I., Klunk, W. E., Mathis, C. A., Morris, J. C., et al. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.2177-05.2005 · Cited by 2,140 · see citing works
Propagation of Tau Misfolding from the Outside to the Inside of a Cell
Frost, B., Jacks, R. L., & Diamond, M. I. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m808759200 · Cited by 1,252 · see citing works
Dynamics of Gray Matter Loss in Alzheimer's Disease
Thompson, P. M., Hayashi, K. M., de Zubicaray, G., Janke, A. L., Rose, S. E., Semple, J., Herman, D., Hong, M. S., Dittmer, S. S., Doddrell, D. M., et al. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-03-00994.2003 · Cited by 1,132 · see citing works
Dementia and Alzheimer Disease Incidence: A Prospective Cohort Study
Kukull, W. A., Higdon, R., Bowen, J. D., McCormick, W. C., Teri, L., Schellenberg, G. D., van Belle, G., Jolley, L., & Larson, E. B. (2002) · Archives of Neurology · doi:10.1001/archneur.59.11.1737 · Cited by 806 · see citing works
Frontal Paralimbic Network Atrophy in Very Mild Behavioral Variant Frontotemporal Dementia
Seeley, W. W., Crawford, R., Rascovsky, K., Kramer, J. H., Weiner, M., Miller, B. L., & Gorno-Tempini, M. L. (2008) · Archives of Neurology · doi:10.1001/archneurol.2007.38 · Cited by 506 · see citing works
Self-citationVillain, N., Desgranges, B., Viader, F., de la Sayette, V., Mezenge, F., Landeau, B., Baron, J.-C., Eustache, F., & Chetelat, G. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1392-08.2008 · Cited by 366 · see citing works
Conformational Diversity of Wild-type Tau Fibrils Specified by Templated Conformation Change
Frost, B., Ollesch, J., Wille, H., & Diamond, M. I. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m805627200 · Cited by 224 · see citing works
Flagged first, then by citations
Research works printed but not linked: 53
- Acosta-Cabronero Julio Williams Guy B Pengas George Nestor Peter J 2010 Absolute diffusivities define the landscape of white matter degeneration in Alzheimer’s disease Brain 133 529 539 19914928
- Almond DP Budd CJ McCullen NJ Georgoulis E Iske A Levesley J 2011 Emergent behaviour in large electrical networks Approximation Algorithms for Complex Systems New York Springer 3 26
- Apostolova LG Steiner CA Akopyan GG Dutton RA Hayashi KM Toga AW Cummings JL Thompson PM 2007 Three-dimensional gray matter atrophy mapping in mild cognitive impairment and mild Alzheimer disease Arch Neurol 64 1489 1495 17923632 PMC3197839
- Barreda JL Zhou HX 2011 A solvable model for the diffusion and reaction of neurotransmitters in a synaptic junction BMC Biophys 4 5 21596000 PMC3093673
- Bartzokis G 2004 Age-related myelin breakdown: a developmental model of cognitive decline and Alzheimer’s disease Neurobiol Aging 25 5 18 author reply 49–62 14675724
- Behrens TEJ Berg HJ Jbabdi S Rushworth MFS Woolrich MW 2007 Probabilistic diffusion tractography with multiple fibre orientations: What can we gain? Neuroimage 34 144 155 17070705 PMC7116582
- Bhalla US 2002 Understanding complex signaling networks through models and metaphors Prog Biophys Mol Biol 81 45 65 12475569
- Boxer AL Miller BL 2005 Clinical features of frontotemporal dementia Alzheimer Dis Assoc Disord 19 Suppl 1 S3 S6 16317256
- Boxer AL Geschwind MD Belfor N Gorno-Tempini ML Schauer GF Miller BL Weiner MW Rosen HJ 2006 Patterns of brain atrophy that differentiate corticobasal degeneration syndrome from progressive supranuclear palsy Arch Neurol 63 81 86 16401739
- Braak H Del Tredici K Schultz C Braak E 2000 Vulnerability of select neuronal types to Alzheimer’s disease Ann N Y Acad Sci 924 53 61 11193802
- Broe M Hodges JR Schofield E Shepherd CE Kril JJ Halliday GM 2003 Staging disease severity in pathologically confirmed cases of frontotemporal dementia Neurology 60 1005 1011 12654969
- Carlo AD 2002 Incidence of dementia, Alzheimer’s disease, and vascular dementia in Italy. The ILSA Study J Am Geriatr Soc 50 41 48 12028245
- Curtis CE D’Esposito M 2003 Persistent activity in the prefrontal cortex during working memory Trends Cogn Sci 7 415 423 12963473
- Du AT Schuff N Kramer JH Rosen HJ Gorno-Tempini ML Rankin K Miller BL Weiner MW 2007 Different regional patterns of cortical thinning in Alzheimer’s disease and frontotemporal dementia Brain 130 1159 1166 17353226 PMC1853284
- Englund E Brun A Alling C 1988 White matter changes in dementia of Alzheimer’s type. Biochemical and neuropathological correlates Brain 111 1425 1439 3208064
- Forman MS 2006 Frontotemporal dementia: clinicopathological correlations Ann Neurol 59 952 962 16718704 PMC2629792
- Frost B Diamond MI 2010 Prion-like mechanisms in neurodegenerative diseases Nat Rev Neurosci 11 155 159 20029438 PMC3648341
- Goldberg II Harel M Malach R 2006 When the brain loses its self: prefrontal inactivation during sensorimotor processing Neuron 50 329 339 16630842
- Gorno-Tempini ML Dronkers NF Rankin KP Ogar JM Phengrasamy L Rosen HJ Johnson JK Weiner MW Miller BL 2004 Cognition and anatomy in three variants of primary progressive aphasia Ann Neurol 55 335 346 14991811 PMC2362399
- Hardy J 2005 Expression of normal sequence pathogenic proteins for neurodegenerative disease contributes to disease risk: “permissive templating” as a general mechanism underlying neurodegeneration Biochem Soc Trans 33 578 581 16042548
- Harvey RJ 2003 The prevalence and causes of dementia in people under the age of 65 years J Neurol Neurosurg Psychiatry 74 1206 1209 12933919 PMC1738690
- He Y Chen Z Evans A 2008 Structural insights into aberrant topological patterns of large-scale cortical networks in Alzheimer’s disease J Neurosci 28 4756 4766 18448652 PMC6670444
- Hess CP Mukherjee P Han ET Xu D Vigneron DB 2006 Q-ball reconstruction of multimodal fiber orientations using the spherical harmonic basis Magn Res Med 56 104 117 16755539
- Iturria-Medina Y Canales-Rodriguez EJ Aleman-Gomez Y Sotero RC Melie-Garcia L 2008 Studying the human brain anatomical network via diffusion-weighted MRI and graph theory Neuroimage 40 1064 1076 18272400
- Jellinger KA Attems J 2010 Prevalence of dementia disorders in the oldest-old: an autopsy study Acta Neuropathol 119 421 433 20204386
- Klauschen F Goldman A Barra V Meyer-Lindenberg A Lundervold A 2009 Evaluation of automated brain MR image segmentation and volume-try methods Hum Brain Mapp 30 1310 1327 18537111 PMC6870639
- Kobayashi M Sato T Sato A Imamura T 2009 Oldest-old dementia in a Japanese memory clinic Brain and Nerve 61 972 978 19697887
- Kondor RI Lafferty J 2002 Diffusion kernels on graphs and other discrete structures Proc. 19th Intl. Conf. on Machine Learning 315 322
- Kuczynski B Targan E Madison C Weiner M Zhang Yu Reed B Chui HC Jagust W 2010 White matter integrity and cortical metabolic associations in aging and dementia Alzheimers Dement 6 54 62 20129319 PMC2817977
- Lo CY Wang PN Chou KH Wang J He Y Lin CP 2010 Diffusion tensor tractography reveals abnormal topological organization in structural cortical networks in Alzheimer’s disease J Neurosci 30 16876 16885 21159959 PMC6634928
- Lomasko T Lumsden CJ 2009 One-hit stochastic decline in a mechanochemical model of cytoskeleton-induced neuron death III: diffusion pulse death zones J Theor Biol 256 104 116 18824176
- Martinez S Cortes J Bullo F 2007 Motion coordination with distributed information IEEE Contr Syst 27 75 88
- McKhann G Drachman D Folstein M Katzman R Price D Stadlan EM 1984 Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease Neurology 34 939 944 6610841
- Morrison PJ 2010 Accurate prevalence and uptake of testing for Huntington’s disease Lancet Neurol 9 1147 21087736
- Neary D Snowden J 1996 Frontotemporal dementia: nosology, neuropsychology, and neuropathology Brain Cogn 31 176 187 8811995
- Neary D Snowden JS Gustafson L Passant U Stuss D Black S Freedman M Kertesz A Robert PH Albert M 1998 Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria Neurology 51 1546 1554 9855500
- Palop JJ Mucke L 2010 Amyloid-β-induced neuronal dysfunction in Alzheimer’s disease: from synapses toward neural networks Nat Neurosci 13 812 818 20581818 PMC3072750
- Palop JJ Chin J Mucke L 2006 A network dysfunction perspective on neurodegenerative diseases Nature 443 768 773 17051202
- Pereira JMS Williams GB Acosta-Cabronero J Pengas G Spillantini MG Xuereb JH Hodges JR Nestor PJ 2009 Atrophy patterns in histologic vs clinical groupings of frontotemporal lobar degeneration Neurology 72 1653 1660 19433738 PMC2827263
- Plassman BL Langa KM Fisher GG Heeringa SG Weir DR Ofstedal MB Burke JR Hurd MD Potter GG Rodgers WL 2007 Prevalence of dementia in the United States: the aging, demographics, and memory study Neuroepidemiology 29 125 132 17975326 PMC2705925
- Rabinovici GD Jagust WJ 2009 Amyloid imaging in aging and dementia: testing the amyloid hypothesis in vivo Behav Neurol 21 117 128 19847050 PMC2804478
- Rabinovici GD Furst AJ Alkalay A Racine CA O’Neil PJ Janabi M Baker SL Agarwal N Bonasera SJ Mormino EC 2010 Increased metabolic vulnerability in early-onset Alzheimer’s disease is not related to amyloid burden Brain 133 512 528 20080878 PMC2858015
- Raj A Chen Y 2011 The wiring economy principle: connectivity determines anatomy in the human brain PLoS ONE 6 e14832 21915250 PMC3168442
- Ratnavalli E Brayne C Dawson K Hodges JR 2002 The prevalence of frontotemporal dementia Neurology 58 1615 1621 12058088
- Rosas HD Salat DH Lee SY Zaleta AK Pappu V Fischl B Greve D Hevelone N Hersch SM 2008 Cerebral cortex and the clinical expression of Huntington’s disease: complexity and heterogeneity Brain 131 1057 1068 18337273 PMC2657201
- Santos SF Pierrot N Octave JN 2010 Network excitability dysfunction in Alzheimer’s disease: insights from in vitro and in vivo models Rev Neurosci 21 153 171 20879690
- Saxena S Caroni P 2011 Selective neuronal vulnerability in neurodegenerative diseases: from stressor thresholds to degeneration Neuron 71 35 48 21745636
- Seeley WW Crawford RK Zhou J Miller BL Greicius MD 2009 Neurodegenerative diseases target large-scale human brain networks Neuron 62 42 52 19376066 PMC2691647
- Shalizi C 2001 Causal architecture, complexity and self-organization in time series and cellular automata PhD thesis University of Wisconsin Madison, WI (http://www.cscs.umich.edu/crshalizi/thesis/)
- Whitwell JL Josephs KA Rossor MN Stevens JM Revesz T Holton JL Al-Sarraj S Godbolt AK Fox NC Warren JD 2005 Magnetic resonance imaging signatures of tissue pathology in frontotemporal dementia Arch Neurol 62 1402 1408 16157747
- Whitwell JL Jack CR Senjem ML Parisi JE Boeve BF Knopman DS Dickson DW Petersen RC Josephs KA 2009 MRI correlates of protein deposition and disease severity in postmortem frontotemporal lobar degeneration Neurodegener Dis 6 106 117 19299900 PMC2745704
- Wu M Rosano C Lopez-Garcia P Carter CS Aizenstein HJ 2007 Optimum template selection for atlas-based segmentation Neuroimage 34 1612 1618 17188896
- Zhou J 2010 Divergent network connectivity changes in behavioural variant frontotemporal dementia and Alzheimer’s disease Brain 133 1352 1367 20410145 PMC2912696
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Leech, R., & Sharp, D. J. (2014) · Brain · doi:10.1093/brain/awt162 · Cited by 2,247 · see citing works
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van den Heuvel, M. P., & Sporns, O. (2013) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2013.09.012 · Cited by 2,123 · see citing works
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Jucker, M., & Walker, L. C. (2013) · Nature · doi:10.1038/nature12481 · Cited by 1,663 · see citing works
Iturria-Medina, Y., Sotero, R. C., Toussaint, P. J., Mateos-Pérez, J. M., Evans, A. C., Initiative, T. A. D. N., Weiner, M. W., Aisen, P., Petersen, R., Jack, C. R., et al. (2016) · Nature Communications · doi:10.1038/ncomms11934 · Cited by 1,202 · see citing works
Self-citationImaging structural co-variance between human brain regions
Alexander-Bloch, A., Giedd, J. N., & Bullmore, E. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3465 · Cited by 1,064 · see citing works
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Sanders, D. W., Kaufman, S. K., DeVos, S. L., Sharma, A. M., Mirbaha, H., Li, A., Barker, S. J., Foley, A. C., Thorpe, J. R., Serpell, L. C., et al. (2014) · Neuron · doi:10.1016/j.neuron.2014.04.047 · Cited by 986 · see citing works
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Brettschneider, J., Tredici, K. D., Lee, V. M.-Y., & Trojanowski, J. Q. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3887 · Cited by 790 · see citing works
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Holmes, B. B., Furman, J. L., Mahan, T. E., Yamasaki, T. R., Mirbaha, H., Eades, W. C., Belaygorod, L., Cairns, N. J., Holtzman, D. M., & Diamond, M. I. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1411649111 · Cited by 696 · see citing works
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Jagust, W. (2018) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0067-3 · Cited by 604 · see citing works
Young, A. L., Marinescu, R. V., Oxtoby, N. P., Bocchetta, M., Yong, K., Firth, N. C., Cash, D. M., Thomas, D. L., Dick, K. M., Cardoso, J., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05892-0 · Cited by 596 · see citing works
Self-citationYanamandra, K., Kfoury, N., Jiang, H., Mahan, T. E., Ma, S., Maloney, S. E., Wozniak, D. F., Diamond, M. I., & Holtzman, D. M. (2013) · Neuron · doi:10.1016/j.neuron.2013.07.046 · Cited by 574 · see citing works
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Yu, M., Sporns, O., & Saykin, A. J. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-021-00529-1 · Cited by 265 · see citing works
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Mandelli, M. L., Vilaplana, E., Brown, J. A., Hubbard, H. I., Binney, R. J., Attygalle, S., Santos-Santos, M. A., Miller, Z. A., Pakvasa, M., Henry, M. L., et al. (2016) · Brain · doi:10.1093/brain/aww195 · Cited by 139 · see citing works
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Stancu, I.-C., Vasconcelos, B., Ris, L., Wang, P., Villers, A., Peeraer, E., Buist, A., Terwel, D., Baatsen, P., Oyelami, T., et al. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1413-4 · Cited by 143 · see citing works
Melo, H. M., Seixas da Silva, G. D. S., Sant’Ana, M. R., Teixeira, C. V. L., Clarke, J. R., Miya Coreixas, V. S., de Melo, B. C., Fortuna, J. T. S., Forny-Germano, L., Ledo, J. H., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.01.072 · Cited by 140 · see citing works
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Mahoney, C. J., Ridgway, G. R., Malone, I. B., Downey, L. E., Beck, J., Kinnunen, K. M., Schmitz, N., Golden, H. L., Rohrer, J. D., Schott, J. M., et al. (2014) · Human Brain Mapping · doi:10.1002/hbm.22468 · Cited by 124 · see citing works
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Mahoney, C. J., Downey, L. E., Ridgway, G. R., Beck, J., Clegg, S., Blair, M., Finnegan, S., Leung, K. K., Yeatman, T., Golden, H., et al. (2012) · Alzheimer's Research & Therapy · doi:10.1186/alzrt144 · Cited by 114 · see citing works
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Chhatwal, J. P., Schultz, A. P., Johnson, K. A., Hedden, T., Jaimes, S., Benzinger, T. L. S., Jack, C., Ances, B. M., Ringman, J. M., Marcus, D. S., et al. (2018) · Brain · doi:10.1093/brain/awy053 · Cited by 101 · see citing works
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Oxtoby, N. P., & Alexander, D. C. (2017) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000460 · Cited by 105 · see citing works
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Wells, J. A., O'Callaghan, J. M., Holmes, H. E., Powell, N. M., Johnson, R. A., Siow, B., Torrealdea, F., Ismail, O., Walker-Samuel, S., Golay, X., et al. (2015) · NeuroImage · doi:10.1016/j.neuroimage.2015.02.023 · Cited by 93 · see citing works
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Downey, L. E., Mahoney, C. J., Buckley, A. H., Golden, H. L., Henley, S. M., Schmitz, N., Schott, J. M., Simpson, I. J., Ourselin, S., Fox, N. C., et al. (2015) · NeuroImage: Clinical · doi:10.1016/j.nicl.2015.06.005 · Cited by 94 · see citing works
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Kim, H. J., Im, K., Kwon, H., Lee, J.-M., Kim, C., Kim, Y. J., Jung, N.-Y., Cho, H., Ye, B. S., Noh, Y., et al. (2015) · Neurology · doi:10.1212/wnl.0000000000001705 · Cited by 85 · see citing works
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Sepulcre, J., Grothe, M. J., Sabuncu, M., Chhatwal, J., Schultz, A. P., Hanseeuw, B., El Fakhri, G., Sperling, R., & Johnson, K. A. (2017) · JAMA Neurology · doi:10.1001/jamaneurol.2017.0263 · Cited by 73 · see citing works
Tahmasian, M., Shao, J., Meng, C., Grimmer, T., Diehl-Schmid, J., Yousefi, B. H., Förster, S., Riedl, V., Drzezga, A., & Sorg, C. (2016) · Journal of Nuclear Medicine · doi:10.2967/jnumed.115.165464 · Cited by 66 · see citing works
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Mandelli, M. L., Welch, A. E., Vilaplana, E., Watson, C., Battistella, G., Brown, J. A., Possin, K. L., Hubbard, H. I., Miller, Z. A., Henry, M. L., et al. (2018) · Cortex · doi:10.1016/j.cortex.2018.08.002 · Cited by 67 · see citing works
Cornblath, E. J., Li, H. L., Changolkar, L., Zhang, B., Brown, H. J., Gathagan, R. J., Olufemi, M. F., Trojanowski, J. Q., Bassett, D. S., Lee, V. M. Y., et al. (2021) · Science Advances · doi:10.1126/sciadv.abg6677 · Cited by 66 · see citing works
Reorganisation of brain networks in frontotemporal dementia and progressive supranuclear palsy
Hughes, L. E., Ghosh, B. C. P., & Rowe, J. B. (2013) · NeuroImage: Clinical · doi:10.1016/j.nicl.2013.03.009 · Cited by 60 · see citing works
Hara, M., Hirokawa, K., Kamei, S., & Uchihara, T. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1097-6 · Cited by 55 · see citing works
Malpetti, M., Jones, P. S., Cope, T. E., Holland, N., Naessens, M., Rouse, M. A., Rittman, T., Savulich, G., Whiteside, D. J., Street, D., et al. (2023) · Annals of Neurology · doi:10.1002/ana.26543 · Cited by 53 · see citing works
Kim, H.-J., Shin, J.-H., Han, C. E., Kim, H. J., Na, D. L., Seo, S. W., & Seong, J.-K. (2016) · Frontiers in Neuroscience · doi:10.3389/fnins.2016.00394 · Cited by 44 · see citing works
Modelling female physiology from head to Toe: impact of sex hormones, menstrual cycle, and pregnancy
Abo, S., Smith, D., Stadt, M., & Layton, A. (2022) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2022.111074 · Cited by 35 · see citing works
Ma, C., Wang, J., Zhang, J., Chen, K., Li, X., Shu, N., Chen, Y., Liu, Z., & Zhang, Z. (2017) · Molecular Neurobiology · doi:10.1007/s12035-016-0224-5 · Cited by 21 · see citing works
Alam, M. M., & Latifi, S. (2025) · doi:10.20944/preprints202506.1854.v1 · Cited by 17 · see citing works
- Authors
- Raj, A., Kuceyeski, A., & Weiner, M.
- Affiliations
- Cornell University (US)
- San Francisco VA Medical Center (US)
- Corresponding author
- Raj, Ashish
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2012-03
- Volume
- 73
- Issue
- 6
- Pages
- 1204-1215
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3623298
- OpenAlex
- W2089691915
- Cited by
- 723
- References
- 9
- Citations by year
- 2026: 62 · 2025: 54 · 2024: 39 · 2023: 39 · 2022: 50 · 2021: 55 · 2020: 63 · 2019: 61 · 2018: 55 · 2017: 42 · 2016: 46 · 2015: 52 · 2014: 37 · 2013: 44 · 2012: 22
- FWCI
- 35.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (1f32eb012404-01)
- National Institute of Neurological Disorders and Stroke (R01NS075425)
- National Institute of Biomedical Imaging and Bioengineering (R21EB008138, F32 EB012404)
- National Center for Research Resources (P41RR023953)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- dementia, Alzheimer's disease, frontotemporal dementia, disease progression, network diffusion model, prion-like propagation, amyloid-beta, brain connectivity networks, tractography, graph theory, persistent mode, differential diagnosis
- MeSH terms
- Adolescent, Adult, Age Factors, Aged, Alzheimer Disease, Atrophy, Biophysics, Brain, Brain Mapping, Dementia, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Models, Neurological, Neural Pathways, Predictive Value of Tests, Psychiatric Status Rating Scales, ROC Curve, Statistics as Topic, Reproducibility of Results, Case-Control Studies, Disease Progression, Young Adult, Frontotemporal Dementia
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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