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PLOS ONE  2013 

White Matter Abnormalities and Structural Hippocampal Disconnections in Amnestic Mild Cognitive Impairment and Alzheimer’s Disease

DOI: 10.1371/journal.pone.0074776

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The purpose of this project was to evaluate white matter degeneration and its impact on hippocampal structural connectivity in patients with amnestic mild cognitive impairment, non-amnestic mild cognitive impairment and Alzheimer’s disease. We estimated white matter fractional anisotropy, mean diffusivity and hippocampal structural connectivity in two independent cohorts. The ADNI cohort included 108 subjects [25 cognitively normal, 21 amnestic mild cognitive impairment, 47 non-amnestic mild cognitive impairment and 15 Alzheimer’s disease]. A second cohort included 34 subjects [15 cognitively normal and 19 amnestic mild cognitive impairment] recruited in Montreal. All subjects underwent clinical and neuropsychological assessment in addition to diffusion and T1 MRI. Individual fractional anisotropy and mean diffusivity maps were generated using FSL-DTIfit. In addition, hippocampal structural connectivity maps expressing the probability of connectivity between the hippocampus and cortex were generated using a pipeline based on FSL-probtrackX. Voxel-based group comparison statistics of fractional anisotropy, mean diffusivity and hippocampal structural connectivity were estimated using Tract-Based Spatial Statistics. The proportion of abnormal to total white matter volume was estimated using the total volume of the white matter skeleton. We found that in both cohorts, amnestic mild cognitive impairment patients had 27-29% white matter volume showing higher mean diffusivity but no significant fractional anisotropy abnormalities. No fractional anisotropy or mean diffusivity differences were observed between non-amnestic mild cognitive impairment patients and cognitively normal subjects. Alzheimer’s disease patients had 66.3% of normalized white matter volume with increased mean diffusivity and 54.3% of the white matter had reduced fractional anisotropy. Reduced structural connectivity was found in the hippocampal connections to temporal, inferior parietal, posterior cingulate and frontal regions only in the Alzheimer’s group. The severity of white matter degeneration appears to be higher in advanced clinical stages, supporting the construct that these abnormalities are part of the pathophysiological processes of Alzheimer’s disease.


[1]  Jack CR Jr, Knopman DS, Jagust WJ, Shaw LM, Aisen PS et al. (2010) Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. Lancet Neurol 9: 119–128. doi:10.1016/S1474-4422(09)70299-6. PubMed: 20083042.
[2]  Braak H, Braak E (1991) Neuropathological staging of Alzheimer-related changes. Acta Neuropathol 82: 239-259.
[3]  Mufson EJ, Binder L, Counts SE, DeKosky ST, de Toledo-Morrell L et al. (2012) Mild cognitive impairment: pathology and mechanisms. Acta Neuropathol 123: 13-30. doi:10.1007/s00401-011-0884-1. PubMed: 22101321.
[4]  Chen TF, Chen YF, Cheng TW, Hua MS, Liu HM et al. (2009) Executive dysfunction and periventricular diffusion tensor changes in amnesic mild cognitive impairment and early Alzheimer’s disease. Hum Brain Mapp 30: 3826-3836. doi:10.1002/hbm.20810. PubMed: 19441023.
[5]  Wang DS, Bennett DA, Mufson EJ, Mattila P, Cochran E et al. (2004) Contribution of changes in ubiquitin and myelin basic protein to age-related cognitive decline. Neurosci Res 48: 93-100. doi:10.1016/j.neures.2003.10.002. PubMed: 14687885.
[6]  Bartzokis G, Cummings JL, Sultzer D, Henderson VW, Nuechterlein KH et al. (2003) White matter structural integrity in healthy aging adults and patients with Alzheimer disease: a magnetic resonance imaging study. Arch Neurol 60: 393–398. doi:10.1001/archneur.60.3.393. PubMed: 12633151.
[7]  Lue LF, Rydel R, Brigham EF, Yang LB, Hampel H et al. (2001) Inflammatory repertoire of Alzheimer’s disease and nondemented elderly microglia in vitro. Glia 35: 72-79. doi:10.1002/glia.1072. PubMed: 11424194.
[8]  Stokin GB, Goldstein LS (2006) Axonal transport and Alzheimer’s disease. Annu Rev Biochem 75: 607-627. PubMed: 16756504.
[9]  Clerx L, Visser PJ, Verhey F, Aalten P (2012) New MRI Markers for Alzheimer’s Disease: A Meta-Analysis of Diffusion Tensor Imaging and a Comparison with Medial Temporal Lobe Measurements. J Alzheimers Dis 29: 405-429. PubMed: 22330833.
[10]  Sexton CE, Mackay CE, Ebmeier KP (2009) A systematic review of diffusion tensor imaging studies in affective disorders. Biological psychiatry.
[11]  Gouw AA, Seewann A, Vrenken H, Van Der Flier WM, Rozemuller JM et al. (2008) Heterogeneity of white matter hyperintensities in Alzheimer’s disease: post-mortem quantitative MRI and neuropathology. Brain 131: 3286-3298. doi:10.1093/brain/awn265. PubMed: 18927145.
[12]  Behrens TE, Woolrich MW, Jenkinson M, Johansen-Berg H, Nunes RG et al. (2003) Characterization and propagation of uncertainty in diffusion-weighted MR imaging. Magn Reson Med 50: 1077-1088. doi:10.1002/mrm.10609. PubMed: 14587019.
[13]  Charlton RA, Barrick TR, McIntyre DJ, Shen Y, O’Sullivan M et al. (2006) White matter damage on diffusion tensor imaging correlates with age-related cognitive decline. Neurology 66: 217-222. doi:10.1212/01.wnl.0000194256.15247.83. PubMed: 16434657.
[14]  Duan JH, Wang HQ, Xu J, Lin X, Chen SQ et al. (2006) White matter damage of patients with Alzheimer? ??s disease correlated with the decreased cognitive function. Surgical and Radiologic Anatomy 28: 150-156.
[15]  Gauthier S, Reisberg B, Zaudig M, Petersen RC, Ritchie K et al. (2006) Mild cognitive impairment. Lancet 367: 1262-1270. doi:10.1016/S0140-6736(06)68542-5. PubMed: 16631882.
[16]  Petersen RC (2004) Mild cognitive impairment as a diagnostic entity. J Intern Med 256: 183-194. doi:10.1111/j.1365-2796.2004.01388.x. PubMed: 15324362.
[17]  Schneider JA, Arvanitakis Z, Leurgans SE, Bennett DA (2009) The neuropathology of probable Alzheimer disease and mild cognitive impairment. Ann Neurol 66: 200-208. doi:10.1002/ana.21706. PubMed: 19743450.
[18]  Petersen RC, Parisi JE, Dickson DW, Johnson KA, Knopman DS et al. (2006) Neuropathologic features of amnestic mild cognitive impairment. Arch Neurol 63: 665-672. doi:10.1001/archneur.63.5.665. PubMed: 16682536.
[19]  Beattie BL (2007) Consent in Alzheimer’s disease research: risk/benefit factors. Can J Neurol Sci 34 Suppl 1: S27-S31. PubMed: 17469678.
[20]  Schmidt M (1996) Rey Auditory Verbal Learning Test: RAVLT: a Handbook: Western. Psychological Services.
[21]  Maes F, Collignon A, Vandermeulen D, Marchal G, Suetens P (1997) Multimodality image registration by maximization of mutual information. IEEE Trans Med Imaging 16: 187-198. PubMed: 9101328.
[22]  Berg L (1988) Clinical dementia rating (CDR). Psychopharmacol Bull 24: 637–639. PubMed: 3249765.
[23]  Folstein MF, Folstein SE, McHugh PR (1975) "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12: 189-198. doi:10.1016/0022-3956(75)90026-6. PubMed: 1202204.
[24]  Aisen PS, Petersen RC, Donohue MC, Gamst A, Raman R et al. (2010) Clinical Core of the Alzheimer’s Disease Neuroimaging Initiative: progress and plans. Alzheimers Dement 6: 239-246. doi:10.1016/j.jalz.2010.05.778. PubMed: 20451872.
[25]  Wechsler D (1987) WMS-R: Wechsler Memory Scale -- Revised: manual. San Antonio: Psychological Corporation.
[26]  Lucas JA, Ivnik RJ, Smith GE, Bohac DL, Tangalos EG et al. (1998) Mayo’s older Americans normative studies: category fluency norms. J Clin Exp Neuropsychol 20: 194-200. doi:10.1076/jcen. PubMed: 9777473.
[27]  Tierney MC, Fisher RH, Lewis AJ, Zorzitto ML, Snow WG et al. (1988) The NINCDS-ADRDA Work Group criteria for the clinical diagnosis of probable Alzheimer’s disease A clinicopathologic study of 57 cases. Neurology 38: 359-359. doi:10.1212/WNL.38.3.359. PubMed: 3347338.
[28]  Eskildsen SF, Coupé P, Fonov V, Manjón JV, Leung KK et al. (2012) BEaST: Brain extraction based on nonlocal segmentation technique. NeuroImage 59: 2362-2373. doi:10.1016/j.neuroimage.2011.09.012. PubMed: 21945694.
[29]  Sled JG, Zijdenbos AP, Evans AC (1998) A nonparametric method for automatic correction of intensity nonuniformity in MRI data. Medical Imaging, IEEE Transactions on 17: 87-97. doi:10.1109/42.668698.
[30]  Fonov V, Evans AC, Botteron K, Almli CR, McKinstry RC et al. (2011) Unbiased average age-appropriate atlases for pediatric studies. NeuroImage 54: 313–327. doi:10.1016/j.neuroimage.2010.07.033. PubMed: 20656036.
[31]  Zijdenbos A, Forghani R, Evans A (1998) Automatic quantification of MS lesions in 3D MRI brain data sets: Validation of INSECT. Medical Image Computing and Computer-Assisted Interventation—MICCAI’ 98. Heidelberg: Springer Verlag Berlin pp. 439-448.
[32]  Collins DE, Evans AC (1997) ANIMAL: validation and applications of non-linear registration-based segmentation. Int J Pattern Recognit Artif Intell 11: 1271-1294. doi:10.1142/S0218001497000597.
[33]  Jenkinson M, Pechaud M, Smith S (2005) ET2: MR-based estimation of brain, skull and scalp surfaces.
[34]  Jenkinson M, Pechaud M, Smith S (2005) ET2: MR-based estimation of brain, skull and scalp surfaces pp. 12-16.
[35]  Behrens TE, Johansen-Berg H, Woolrich MW, Smith SM, Wheeler-Kingshott CA et al. (2003) Non-invasive mapping of connections between human thalamus and cortex using diffusion imaging. Nat Neurosci 6: 750-757. doi:10.1038/nn1075. PubMed: 12808459.
[36]  Smith SM, Jenkinson M, Johansen-Berg H, Rueckert D, Nichols TE et al. (2006) Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. NeuroImage 31: 1487-1505. doi:10.1016/j.neuroimage.2006.02.024. PubMed: 16624579.
[37]  Collins DL, Neelin P, Peters TM, Evans AC (1994) Automatic 3D intersubject registration of MR volumetric data in standardized Talairach space. J Comput Assist Tomogr 18: 192–205. doi:10.1097/00004728-199403000-00005. PubMed: 8126267.
[38]  Nichols TE, Holmes AP (2001) Nonparametric permutation tests for functional neuroimaging: a primer with examples. Hum Brain Mapp 15: 1-25. PubMed: 11747097.
[39]  Miller AK, Alston RL, Corsellis JA (2008) Variation with age in the volumes of grey and white matter in the cerebral hemispheres of man: measurements with an image analyser. Neuropathol Appl Neurobiol 6: 119-132. PubMed: 7374914.
[40]  Vollmar C, O’Muircheartaigh J, Barker GJ, Symms MR, Thompson P et al. (2010) Identical, but not the same: intra-site and inter-site reproducibility of fractional anisotropy measures on two 3.0T scanners. Neuroimage 51: 1384-1394.
[41]  Bosch B, Arenaza-Urquijo EM, Rami L, Sala-Llonch R, Junqué C et al. (2012) Multiple DTI index analysis in normal aging, amnestic MCI and AD. Relationship with neuropsychological performance. Neurobiol Aging 33: 61-74. doi:10.1016/j.neurobiolaging.2010.02.004. PubMed: 20371138.
[42]  O’Dwyer L, Lamberton F, Bokde AL, Ewers M, Faluyi YO et al. (2011) Multiple indices of diffusion identifies white matter damage in mild cognitive impairment and Alzheimer’s disease. PLOS ONE 6: e21745. doi:10.1371/journal.pone.0021745. PubMed: 21738785.
[43]  Cho H, Yang DW, Shon YM, Kim BS, Kim YI et al. (2008) Abnormal Integrity of Corticocortical Tracts in Mild Cognitive Impairment: A Diffusion Tensor Imaging Study. J Korean Med Sci 23: 477–483. doi:10.3346/jkms.2008.23.3.477. PubMed: 18583886.
[44]  Chua TC, Wen W, Slavin MJ, Sachdev PS (2008) Diffusion tensor imaging in mild cognitive impairment and Alzheimer’s disease: a review. Curr Opin Neurol 21: 83-92. doi:10.1097/WCO.0b013e3282f4594b. PubMed: 18180656.
[45]  Fellgiebel A, Wille P, M uuml ller MJ, Winterer G, Scheurich A, et al (2004) Ultrastructural Hippocampal and White Matter Alterations in Mild Cognitive Impairment: A Diffusion Tensor Imaging Study. Dement Geriatr Cogn Disord 18: 101-108. doi:10.1159/000077817. PubMed: 15087585.
[46]  Rose SE, Chen F, Chalk JB, Zelaya FO, Strugnell WE et al. (2000) Loss of connectivity in Alzheimer’s disease: an evaluation of white matter tract integrity with colour coded MR diffusion tensor imaging. J Neurol Neurosur Ps 69: 528-530. doi:10.1136/jnnp.69.4.528. PubMed: 10990518.
[47]  Good CD, Scahill RI, Fox NC, Ashburner J, Friston KJ et al. (2002) Automatic Differentiation of Anatomical Patterns in the Human Brain: Validation with Studies of Degenerative Dementias. NeuroImage 17: 29-46. doi:10.1006/nimg.2002.1202. PubMed: 12482066.
[48]  Good CD (2001) A Voxel-Based Morphometric Study of Ageing in 465 Normal Adult Human Brains. NeuroImage 14: 21-36. doi:10.1006/nimg.2001.0786. PubMed: 11525331.
[49]  Yasmin H, Nakata Y, Aoki S, Abe O, Sato N et al. (2008) Diffusion abnormalities of the uncinate fasciculus in Alzheimer’s disease: diffusion tensor tract-specific analysis using a new method to measure the core of the tract. Neuroradiology 50: 293-299. doi:10.1007/s00234-007-0353-7. PubMed: 18246334.
[50]  Agosta F, Pievani M, Sala S, Geroldi C, Galluzzi S et al. (2011) White matter damage in Alzheimer disease and its relationship to gray matter atrophy. Radiology 258: 853-863. doi:10.1148/radiol.10101284. PubMed: 21177393.
[51]  Douaud G, Jbabdi S, Behrens TE, Menke RA, Gass A et al. (2011) DTI measures in crossing-fibre areas: increased diffusion anisotropy reveals early white matter alteration in MCI and mild Alzheimer’s disease. NeuroImage 55: 880-890. doi:10.1016/j.neuroimage.2010.12.008. PubMed: 21182970.
[52]  Fellgiebel A, Wille P, Müller MJ, Winterer G, Scheurich A et al. (2004) Ultrastructural hippocampal and white matter alterations in mild cognitive impairment: a diffusion tensor imaging study. Dement Geriatr Cogn Disord 18: 101-108. doi:10.1159/000077817. PubMed: 15087585.
[53]  Chua TC, Wen W, Chen X, Kochan N, Slavin MJ et al. (2009) Diffusion tensor imaging of the posterior cingulate is a useful biomarker of mild cognitive impairment. The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 17: 602-613. doi:10.1097/JGP.0b013e3181a76e0b. PubMed: 19546655.
[54]  Kiuchi K, Morikawa M, Taoka T, Nagashima T, Yamauchi T et al. (2009) Abnormalities of the uncinate fasciculus and posterior cingulate fasciculus in mild cognitive impairment and early Alzheimer's disease: A diffusion tensor tractography study. Brain Res 1287: 184-191. doi:10.1016/j.brainres.2009.06.052. PubMed: 19559010.
[55]  Medina D, DeToledo-Morrell L, Urresta F, Gabrieli JD, Moseley M et al. (2006) White matter changes in mild cognitive impairment and AD: A diffusion tensor imaging study. Neurobiol Aging 27: 663-672. doi:10.1016/j.neurobiolaging.2005.03.026. PubMed: 16005548.
[56]  Parente DB, Gasparetto EL, da Cruz LC Jr, Domingues RC, Baptista AC, et al. (2008) Potential role of diffusion tensor MRI in the differential diagnosis of mild cognitive impairment and Alzheimer's disease. American Journal of Roentgenology 190: 1369-1374. doi:10.2214/AJR.07.2617. PubMed: 18430857. doi:10.2214/AJR.07.2617. PubMed: 18430857.
[57]  Stahl R, Dietrich O, Teipel SJ, Hampel H, Reiser MF et al. (2007) White Matter Damage in Alzheimer Disease and Mild Cognitive Impairment: Assessment with Diffusion-Tensor MR Imaging and Parallel Imaging Techniques. Radiology 243: 483-492. doi:10.1148/radiol.2432051714. PubMed: 17456872.
[58]  Ukmar M, Makuc E, Onor ML, Garbin G, Trevisiol M et al. (2008) Risonanza magnetica con tensori di diffusione nella valutazione delle alterazioni della sostanza bianca nei pazienti con malattia di Alzheimer e nei pazienti con mild cognitive impairment. Radiol Med 113: 915-922. doi:10.1007/s11547-008-0286-1. PubMed: 18618077.
[59]  Zhang Y, Schuff N, Jahng GH, Bayne W, Mori S et al. (2007) Diffusion tensor imaging of cingulum fibers in mild cognitive impairment and Alzheimer disease. Neurology 68: 13-19. doi:10.1212/01.wnl.0000259403.31527.ef. PubMed: 17200485.
[60]  Zhuang L, Wen W, Zhu W, Trollor J, Kochan N et al. (2010) White matter integrity in mild cognitive impairment: a tract-based spatial statistics study. Neuroimage 53: 16-25. doi:10.1016/j.neuroimage.2010.05.068. PubMed: 20595067.
[61]  Bozzali M, Falini A, Franceschi M, Cercignani M, Zuffi M et al. (2002) White matter damage in Alzheimer’s disease assessed in vivo using diffusion tensor magnetic resonance imaging. J Neurol Neurosurg, Psychiatr 72: 742-746. doi:10.1136/jnnp.72.6.742. PubMed: 12023417.
[62]  Choi SJ (2005) Diffusion Tensor Imaging of Frontal White Matter Microstructure in Early Alzheimer's Disease: A Preliminary Study. J Geriatr Psychiatry Neurol 18: 12-19. doi:10.1177/0891988704271763. PubMed: 15681623.
[63]  Ibrahim I, Horacek J, Bartos A, Hajek M, Ripova D et al. (2009) Combination of voxel based morphometry and diffusion tensor imaging in patients with Alzheimer's disease. Neuro endocrinology letters 30: 39-45.
[64]  Medina D, Detoledo-Morrell L, Urresta F, Gabrieli JDE, Moseley M et al. (2006) White matter changes in mild cognitive impairment and AD: A diffusion tensor imaging study. Neurobiol Aging 27: 663-672. doi:10.1016/j.neurobiolaging.2005.03.026. PubMed: 16005548.
[65]  Stricker NH, Schweinsburg BC, Delano-Wood L, Wierenga CE, Bangen KJ et al. (2009) Decreased white matter integrity in late-myelinating fiber pathways in Alzheimer’s disease supports retrogenesis. NeuroImage 45: 10-16. doi:10.1016/j.neuroimage.2008.11.027. PubMed: 19100839.
[66]  Takahashi E, Ohki K, Kim DS (2007) Diffusion tensor studies dissociated two fronto-temporal pathways in the human memory system. NeuroImage 34: 827-838. doi:10.1016/j.neuroimage.2006.10.009. PubMed: 17123836.
[67]  Taoka T, Iwasaki S, Sakamoto M, Nakagawa H, Fukusumi A et al. (2006) Diffusion anisotropy and diffusivity of white matter tracts within the temporal stem in Alzheimer disease: evaluation of the " tract of interest" by diffusion tensor tractography. AJNR Am J Neuroradiol 27: 1040-1045. PubMed: 16687540.
[68]  Teipel SJ, Stahl R, Dietrich O, Schoenberg SO, Perneczky R et al. (2007) Multivariate network analysis of fiber tract integrity in Alzheimer’s disease. NeuroImage 34: 985-995. doi:10.1016/j.neuroimage.2006.07.047. PubMed: 17166745.
[69]  Salat DH, Tuch DS, van der Kouwe AJ, Greve DN, Pappu V et al. (2010) White matter pathology isolates the hippocampal formation in Alzheimer’s disease. Neurobiol Aging 31: 244-256. doi:10.1016/j.neurobiolaging.2008.03.013. PubMed: 18455835.
[70]  Brückner G, Hausen D, H?rtig W, Drlicek M, Arendt T et al. (1999) Cortical areas abundant in extracellular matrix chondroitin sulphate proteoglycans are less affected by cytoskeletal changes in Alzheimer’s disease. Neuroscience 92: 791-805. doi:10.1016/S0306-4522(99)00071-8. PubMed: 10426522.
[71]  de la Monte SM (1989) Quantitation of cerebral atrophy in preclinical and end-stage alzheimer’s disease. Ann Neurol 25: 450-459. doi:10.1002/ana.410250506. PubMed: 2774485.
[72]  Krstic D, Knuesel I (2012) Deciphering the mechanism underlying late-onset Alzheimer disease. Nat. Rev Neurol.
[73]  Cagnin A, Kassiou M, Meikle SR, Banati RB (2006) In vivo evidence for microglial activation in neuro degenerative dementia. Acta Neurol Scand: 107-114.
[74]  Okello A, Edison P, Archer HA, Turkheimer FE, Kennedy J et al. (2009) Microglial activation and amyloid deposition in mild cognitive impairment: a PET study. Neurology 72: 56-62. doi:10.1212/01.wnl.0000345004.84188.b9. PubMed: 19122031.
[75]  Carter SF, Sch?ll M, Almkvist O, Wall A, Engler H et al. (2012) Evidence for astrocytosis in prodromal Alzheimer disease provided by 11C-deuterium-L-deprenyl: a multitracer PET paradigm combining 11C-Pittsburgh compound B and 18F-FDG. J Nucl Med 53: 37-46. doi:10.2967/jnumed.110.087031. PubMed: 22213821.
[76]  Nestor SM, Rupsingh R, Borrie M, Smith M, Accomazzi V et al. (2008) Ventricular enlargement as a possible measure of Alzheimer’s disease progression validated using the Alzheimer’s Disease Neuroimaging Initiative database. Brain 131: 2443-2454. doi:10.1093/brain/awn146. PubMed: 18669512.
[77]  Goldman-Rakic PS, Selemon LD, Schwartz ML (1984) Dual pathways connecting the dorsolateral prefrontal cortex with the hippocampal formation and parahippocampal cortex in the rhesus monkey. Neuroscience 12: 719-743. doi:10.1016/0306-4522(84)90166-0. PubMed: 6472617.
[78]  Augustinack JC, Magnain C, Reuter M, van der Kouwe AJW, Boas D et al. (2013) MRI Parcellation of Ex Vivo Medial Temporal Lobe. NeuroImage. PubMed: 23702414.
[79]  Barbas H, Blatt GJ (1995) Topographically specific hippocampal projections target functionally distinct prefrontal areas in the rhesus monkey. Hippocampus 5: 511-533. doi:10.1002/hipo.450050604. PubMed: 8646279.
[80]  Blatt GJ, Rosene DL (1998) Organization of direct hippocampal efferent projections to the cerebral cortex of the rhesus monkey: projections from CA1, prosubiculum, and subiculum to the temporal lobe. J Comp Neurol 392: 92-114. doi:10.1002/(SICI)1096-9861(19980302)392:1. PubMed: 9482235.
[81]  Morris R, Pandya DN, Petrides M (1999) Fiber system linking the mid-dorsolateral frontal cortex with the retrosplenial/presubicular region in the rhesus monkey. J Comp Neurol 407: 183-192. doi:10.1002/(SICI)1096-9861(19990503)407:2. PubMed: 10213090.
[82]  Seltzer B, Van Hoesen GW (1979) A direct inferior parietal lobule projection to the presubiculum in the rhesus monkey. Brain Res 179: 157–161. doi:10.1016/0006-8993(79)90499-2. PubMed: 116714.
[83]  Insausti R, Amaral DG (2004) Insausti: Hippocampal formation - Google Scholar. The human nervous system.
[84]  Duvernoy HM (2005) The human hippocampus: functional anatomy, vascularization and serial sections with MRI. Springer Verlag.
[85]  Wang K, Liang M, Wang L, Tian L, Zhang X et al. (2006) Altered functional connectivity in early Alzheimer’s disease: A resting-state fMRI study. Hum Brain Mapp 28: 967-978.
[86]  Wang L, Zang Y, He Y, Liang M, Zhang X et al. (2006) Changes in hippocampal connectivity in the early stages of Alzheimer’s disease: evidence from resting state fMRI. NeuroImage 31: 496-504. doi:10.1016/j.neuroimage.2005.12.033. PubMed: 16473024.
[87]  Herholz K, Salmon E, Perani D, Baron JC, Holthoff V et al. (2002) Discrimination between Alzheimer dementia and controls by automated analysis of multicenter FDG PET. NeuroImage 17: 302-316. doi:10.1006/nimg.2002.1208. PubMed: 12482085.
[88]  Villain N, Desgranges B, Viader F, De La Sayette V, Mézenge F et al. (2008) Relationships between hippocampal atrophy, white matter disruption, and gray matter hypometabolism in Alzheimer’s disease. J Neurosci 28: 6174-6181. doi:10.1523/JNEUROSCI.1392-08.2008. PubMed: 18550759.
[89]  Villain N, Fouquet M, Baron JC, Mézenge F, Landeau B et al. (2010) Sequential relationships between grey matter and white matter atrophy and brain metabolic abnormalities in early Alzheimer’s disease. Brain 133: 3301-3314. doi:10.1093/brain/awq203. PubMed: 20688814.
[90]  Delbeuck X, Van der Linden M, Collette F (2003) Alzheimer’Disease as a Disconnection Syndrome? Neuropsychol Rev 13: 79-92. doi:10.1023/A:1023832305702. PubMed: 12887040.
[91]  Giorgio A, Watkins KE, Chadwick M, James S, Winmill L et al. (2010) Longitudinal changes in grey and white matter during adolescence. Neuroimage 49: 94-103. doi:10.1016/j.neuroimage.2009.08.003. PubMed: 19679191.
[92]  Roosendaal SD, Geurts JJ, Vrenken H, Hulst HE, Cover KS et al. (2009) Regional DTI differences in multiple sclerosis patients. Neuroimage 44: 1397-1403. doi:10.1016/j.neuroimage.2008.10.026. PubMed: 19027076.


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