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. 2014 Feb 27;30(2):198–206. doi: 10.1007/s12264-013-1407-y

Advances in longitudinal studies of amnestic mild cognitive impairment and Alzheimer’s disease based on multi-modal MRI techniques

Zhongjie Hu 1,2, Liyong Wu 1, Jianping Jia 1,3, Ying Han 1,3,✉
PMCID: PMC5562653  PMID: 24574084

Abstract

Amnestic mild cognitive impairment (aMCI) is a prodromal stage of Alzheimer’s disease (AD), and 75%–80% of aMCI patients finally develop AD. So, early identification of patients with aMCI or AD is of great significance for prevention and intervention. According to cross-sectional studies, it is known that the hippocampus, posterior cingulate cortex, and corpus callosum are key areas in studies based on structural MRI (sMRI), functional MRI (fMRI), and diffusion tensor imaging (DTI) respectively. Recently, longitudinal studies using each MRI modality have demonstrated that the neuroimaging abnormalities generally involve the posterior brain regions at the very beginning and then gradually affect the anterior areas during the progression of aMCI to AD. However, it is not known whether follow-up studies based on multi-modal neuroimaging techniques (e.g., sMRI, fMRI, and DTI) can help build effective MRI models that can be directly applied to the screening and diagnosis of aMCI and AD. Thus, in the future, large-scale multi-center follow-up studies are urgently needed, not only to build an MRI diagnostic model that can be used on a single person, but also to evaluate the variability and stability of the model in the general population. In this review, we present longitudinal studies using each MRI modality separately, and then discuss the future directions in this field.

Keywords: magnetic resonance imaging, amnestic mild cognitive impairment, Alzheimer’s disease, multimodality, longitudinal studies

References

  • [1].Kaye JA, Swihart T, Howieson D, Dame A, Moore MM, Karnos T, et al. Volume loss of the hippocampus and temporal lobe in healthy elderly persons destined to develop dementia. Neurology. 1997;48:1297–1304. doi: 10.1212/WNL.48.5.1297. [DOI] [PubMed] [Google Scholar]
  • [2].Whitwell JL, Shiung MM, Przybelski SA, Weigand SD, Knopman DS, Boeve BF, et al. MRI patterns of atrophy associated with progression to AD in amnestic mild cognitive impairment. Neurology. 2008;70:512–520. doi: 10.1212/01.wnl.0000280575.77437.a2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [3].McDonald CR, McEvoy LK, Gharapetian L, Fennema-Notestine C, Hagler DJ, Jr., Holland D, et al. Regional rates of neocortical atrophy from normal aging to early Alzheimer disease. Neurology. 2009;73:457–465. doi: 10.1212/WNL.0b013e3181b16431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [4].Korf ES, Wahlund LO, Visser PJ, Scheltens P. Medial temporal lobe atrophy on MRI predicts dementia in patients with mild cognitive impairment. Neurology. 2004;63:94–100. doi: 10.1212/01.WNL.0000133114.92694.93. [DOI] [PubMed] [Google Scholar]
  • [5].Prasad K, Wiryasaputra L, Ng A, Kandiah N. White matter disease independently predicts progression from mild cognitive impairment to Alzheimer’s disease in a clinic cohort. Dement Geriatr Cogn Disord. 2011;31:431–434. doi: 10.1159/000330019. [DOI] [PubMed] [Google Scholar]
  • [6].Bakkour A, Morris JC, Dickerson BC. The cortical signature of prodromal AD: regional thinning predicts mild AD dementia. Neurology. 2009;72:1048–1055. doi: 10.1212/01.wnl.0000340981.97664.2f. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [7].Plant C, Teipel SJ, Oswald A, Bohm C, Meindl T, Mourao-Miranda J, et al. Automated detection of brain atrophy patterns based on MRI for the prediction of Alzheimer’s disease. Neuroimage. 2010;50:162–174. doi: 10.1016/j.neuroimage.2009.11.046. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [8].Desikan RS, Fischl B, Cabral HJ, Kemper TL, Guttmann CR, Blacker D, et al. MRI measures of temporoparietal regions show differential rates of atrophy during prodromal AD. Neurology. 2008;71:819–825. doi: 10.1212/01.wnl.0000320055.57329.34. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [9].Killiany RJ, Gomez-Isla T, Moss M, Kikinis R, Sandor T, Jolesz F, et al. Use of structural magnetic resonance imaging to predict who will get Alzheimer’s disease. Ann Neurol. 2000;47:430–439. doi: 10.1002/1531-8249(200004)47:4<430::AID-ANA5>3.0.CO;2-I. [DOI] [PubMed] [Google Scholar]
  • [10].Henneman WJ, Sluimer JD, Barnes J, van der Flier WM, Sluimer IC, Fox NC, et al. Hippocampal atrophy rates in Alzheimer disease: added value over whole brain volume measures. Neurology. 2009;72:999–1007. doi: 10.1212/01.wnl.0000344568.09360.31. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [11].Morra JH, Tu Z, Apostolova LG, Green AE, Avedissian C, Madsen SK, et al. Automated mapping of hippocampal atrophy in 1-year repeat MRI data from 490 subjects with Alzheimer’s disease, mild cognitive impairment, and elderly controls. Neuroimage. 2009;45:S3–15. doi: 10.1016/j.neuroimage.2008.10.043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [12].den Heijer T, van der Lijn F, Koudstaal PJ, Hofman A, van der Lugt A, Krestin GP, et al. A 10-year follow-up of hippocampal volume on magnetic resonance imaging in early dementia and cognitive decline. Brain. 2010;133:1163–1172. doi: 10.1093/brain/awq048. [DOI] [PubMed] [Google Scholar]
  • [13].Leung KK, Bartlett JW, Barnes J, Manning EN, Ourselin S, Fox NC. Cerebral atrophy in mild cognitive impairment and Alzheimer disease: rates and acceleration. Neurology. 2013;80:648–654. doi: 10.1212/WNL.0b013e318281ccd3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [14].Honea RA, Swerdlow RH, Vidoni ED, Burns JM. Progressive regional atrophy in normal adults with a maternal history of Alzheimer disease. Neurology. 2011;76:822–829. doi: 10.1212/WNL.0b013e31820e7b74. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [15].den Heijer T, Geerlings MI, Hoebeek FE, Hofman A, Koudstaal PJ, Breteler MM. Use of hippocampal and amygdalar volumes on magnetic resonance imaging to predict dementia in cognitively intact elderly people. Arch Gen Psychiatry. 2006;63:57–62. doi: 10.1001/archpsyc.63.1.57. [DOI] [PubMed] [Google Scholar]
  • [16].Mungas D, Harvey D, Reed BR, Jagust WJ, DeCarli C, Beckett L, et al. Longitudinal volumetric MRI change and rate of cognitive decline. Neurology. 2005;65:565–571. doi: 10.1212/01.wnl.0000172913.88973.0d. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [17].van de Pol LA, van der Flier WM, Korf ES, Fox NC, Barkhof F, Scheltens P. Baseline predictors of rates of hippocampal atrophy in mild cognitive impairment. Neurology. 2007;69:1491–1497. doi: 10.1212/01.wnl.0000277458.26846.96. [DOI] [PubMed] [Google Scholar]
  • [18].Haight TJ, Jagust WJ. Relative contributions of biomarkers in Alzheimer’s disease. Ann Epidemiol. 2012;22:868–875. doi: 10.1016/j.annepidem.2012.09.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [19].Longstreth WT, Jr, Arnold AM, Beauchamp NJ, Jr, Manolio TA, Lefkowitz D, Jungreis C, et al. Incidence, manifestations, and predictors of worsening white matter on serial cranial magnetic resonance imaging in the elderly: the Cardiovascular Health Study. Stroke. 2005;36:56–61. doi: 10.1161/01.STR.0000149625.99732.69. [DOI] [PubMed] [Google Scholar]
  • [20].Maillard P, Carmichael O, Fletcher E, Reed B, Mungas D, DeCarli C. Coevolution of white matter hyperintensities and cognition in the elderly. Neurology. 2012;79:442–448. doi: 10.1212/WNL.0b013e3182617136. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [21].Garde E, Mortensen EL, Krabbe K, Rostrup E, Larsson HB. Relation between age-related decline in intelligence and cerebral white-matter hyperintensities in healthy octogenarians: a longitudinal study. Lancet. 2000;356:628–634. doi: 10.1016/S0140-6736(00)02604-0. [DOI] [PubMed] [Google Scholar]
  • [22].Fazekas F, Kleinert R, Offenbacher H, Schmidt R, Kleinert G, Payer F, et al. Pathologic correlates of incidental MRI white matter signal hyperintensities. Neurology. 1993;43:1683–1689. doi: 10.1212/WNL.43.9.1683. [DOI] [PubMed] [Google Scholar]
  • [23].Schmidt R, Enzinger C, Ropele S, Schmidt H, Fazekas F. Progression of cerebral white matter lesions: 6-year results of the Austrian Stroke Prevention Study. Lancet. 2003;361:2046–2048. doi: 10.1016/S0140-6736(03)13616-1. [DOI] [PubMed] [Google Scholar]
  • [24].Vermeer SE, Prins ND, den Heijer T, Hofman A, Koudstaal PJ, Breteler MM. Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med. 2003;348:1215–1222. doi: 10.1056/NEJMoa022066. [DOI] [PubMed] [Google Scholar]
  • [25].Brickman AM, Honig LS, Scarmeas N, Tatarina O, Sanders L, Albert MS, et al. Measuring cerebral atrophy and white matter hyperintensity burden to predict the rate of cognitive decline in Alzheimer disease. Arch Neurol. 2008;65:1202–1208. doi: 10.1001/archneur.65.9.1202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [26].Smith EE, Egorova S, Blacker D, Killiany RJ, Muzikansky A, Dickerson BC, et al. Magnetic resonance imaging white matter hyperintensities and brain volume in the prediction of mild cognitive impairment and dementia. Arch Neurol. 2008;65:94–100. doi: 10.1001/archneurol.2007.23. [DOI] [PubMed] [Google Scholar]
  • [27].DeCarli C, Mungas D, Harvey D, Reed B, Weiner M, Chui H, et al. Memory impairment, but not cerebrovascular disease, predicts progression of MCI to dementia. Neurology. 2004;63:220–227. doi: 10.1212/01.WNL.0000130531.90205.EF. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [28].Carlson NE, Moore MM, Dame A, Howieson D, Silbert LC, Quinn JF, et al. Trajectories of brain loss in aging and the development of cognitive impairment. Neurology. 2008;70:828–833. doi: 10.1212/01.wnl.0000280577.43413.d9. [DOI] [PubMed] [Google Scholar]
  • [29].Jack CR, Jr, Weigand SD, Shiung MM, Przybelski SA, O’Brien PC, Gunter JL, et al. Atrophy rates accelerate in amnestic mild cognitive impairment. Neurology. 2008;70:1740–1752. doi: 10.1212/01.wnl.0000281688.77598.35. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [30].Jack CR, Jr, Shiung MM, Weigand SD, O’Brien PC, Gunter JL, Boeve BF, et al. Brain atrophy rates predict subsequent clinical conversion in normal elderly and amnestic MCI. Neurology. 2005;65:1227–1231. doi: 10.1212/01.wnl.0000180958.22678.91. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [31].Sluimer JD, van der Flier WM, Karas GB, Fox NC, Scheltens P, Barkhof F, et al. Whole-brain atrophy rate and cognitive decline: longitudinal MR study of memory clinic patients. Radiology. 2008;248:590–598. doi: 10.1148/radiol.2482070938. [DOI] [PubMed] [Google Scholar]
  • [32].Rusinek H, De Santi S, Frid D, Tsui WH, Tarshish CY, Convit A, et al. Regional brain atrophy rate predicts future cognitive decline: 6-year longitudinal MR imaging study of normal aging. Radiology. 2003;229:691–696. doi: 10.1148/radiol.2293021299. [DOI] [PubMed] [Google Scholar]
  • [33].Risacher SL, Shen L, West JD, Kim S, McDonald BC, Beckett LA, et al. Longitudinal MRI atrophy biomarkers: relationship to conversion in the ADNI cohort. Neurobiol Aging. 2010;31:1401–1418. doi: 10.1016/j.neurobiolaging.2010.04.029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [34].Silbert LC, Quinn JF, Moore MM, Corbridge E, Ball MJ, Murdoch G, et al. Changes in premorbid brain volume predict Alzheimer’s disease pathology. Neurology. 2003;61:487–492. doi: 10.1212/01.WNL.0000079053.77227.14. [DOI] [PubMed] [Google Scholar]
  • [35].Vemuri P, Whitwell JL, Kantarci K, Josephs KA, Parisi JE, Shiung MS, et al. Antemortem MRI based STructural Abnormality iNDex (STAND)-scores correlate with postmortem Braak neurofibrillary tangle stage. Neuroimage. 2008;42:559–567. doi: 10.1016/j.neuroimage.2008.05.012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [36].Binnewijzend MA, Schoonheim MM, Sanz-Arigita E, Wink AM, van der Flier WM, Tolboom N, et al. Resting-state fMRI changes in Alzheimer’s disease and mild cognitive impairment. Neurobiol Aging. 2012;33:2018–2028. doi: 10.1016/j.neurobiolaging.2011.07.003. [DOI] [PubMed] [Google Scholar]
  • [37].Bai F, Watson DR, Shi Y, Wang Y, Yue C, Teng Y, et al. Specifically progressive deficits of brain functional marker in amnestic type mild cognitive impairment. PLoS One. 2011;6:e24271. doi: 10.1371/journal.pone.0024271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [38].Wang Z, Liang P, Jia X, Jin G, Song H, Han Y, et al. The baseline and longitudinal changes of PCC connectivity in mild cognitive impairment: a combined structure and resting-state fMRI study. PLoS One. 2012;7:e36838. doi: 10.1371/journal.pone.0036838. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [39].Bai F, Xie C, Watson DR, Shi Y, Yuan Y, Wang Y, et al. Aberrant hippocampal subregion networks associated with the classifications of aMCI subjects: a longitudinal resting-state study. PLoS One. 2011;6:e29288. doi: 10.1371/journal.pone.0029288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [40].Damoiseaux JS, Prater KE, Miller BL, Greicius MD. Functional connectivity tracks clinical deterioration in Alzheimer’s disease. Neurobiol Aging. 2012;33:828 e819–830. doi: 10.1016/j.neurobiolaging.2011.06.024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [41].Bai F, Liao W, Watson DR, Shi Y, Yuan Y, Cohen AD, et al. Mapping the altered patterns of cerebellar resting-state function in longitudinal amnestic mild cognitive impairment patients. J Alzheimers Dis. 2011;23:87–99. doi: 10.3233/JAD-2010-101533. [DOI] [PubMed] [Google Scholar]
  • [42].Vannini P, Almkvist O, Dierks T, Lehmann C, Wahlund LO. Reduced neuronal efficacy in progressive mild cognitive impairment: a prospective fMRI study on visuospatial processing. Psychiatry Res. 2007;156:43–57. doi: 10.1016/j.pscychresns.2007.02.003. [DOI] [PubMed] [Google Scholar]
  • [43].Miller SL, Fenstermacher E, Bates J, Blacker D, Sperling RA, Dickerson BC. Hippocampal activation in adults with mild cognitive impairment predicts subsequent cognitive decline. J Neurol Neurosurg Psychiatry. 2008;79:630–635. doi: 10.1136/jnnp.2007.124149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [44].O’Brien JL, O’Keefe KM, LaViolette PS, DeLuca AN, Blacker D, Dickerson BC, et al. Longitudinal fMRI in elderly reveals loss of hippocampal activation with clinical decline. Neurology. 2010;74:1969–1976. doi: 10.1212/WNL.0b013e3181e3966e. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [45].Petrella JR, Prince SE, Wang L, Hellegers C, Doraiswamy PM. Prognostic value of posteromedial cortex deactivation in mild cognitive impairment. PLoS One. 2007;2:e1104. doi: 10.1371/journal.pone.0001104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [46].Kochan NA, Breakspear M, Valenzuela M, Slavin MJ, Brodaty H, Wen W, et al. Cortical responses to a graded working memory challenge predict functional decline in mild cognitive impairment. Biol Psychiatry. 2011;70:123–130. doi: 10.1016/j.biopsych.2011.03.006. [DOI] [PubMed] [Google Scholar]
  • [47].Petrella JR, Sheldon FC, Prince SE, Calhoun VD, Doraiswamy PM. Default mode network connectivity in stable vs progressive mild cognitive impairment. Neurology. 2011;76:511–517. doi: 10.1212/WNL.0b013e31820af94e. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [48].Jones DK, Lythgoe D, Horsfield MA, Simmons A, Williams SC, Markus HS. Characterization of white matter damage in ischemic leukoaraiosis with diffusion tensor MRI. Stroke. 1999;30:393–397. doi: 10.1161/01.STR.30.2.393. [DOI] [PubMed] [Google Scholar]
  • [49].Scola E, Bozzali M, Agosta F, Magnani G, Franceschi M, Sormani MP, et al. A diffusion tensor MRI study of patients with MCI and AD with a 2-year clinical follow-up. J Neurol Neurosurg Psychiatry. 2010;81:798–805. doi: 10.1136/jnnp.2009.189639. [DOI] [PubMed] [Google Scholar]
  • [50].Teipel SJ, Meindl T, Wagner M, Stieltjes B, Reuter S, Hauenstein KH, et al. Longitudinal changes in fiber tract integrity in healthy aging and mild cognitive impairment: a DTI follow-up study. J Alzheimers Dis. 2010;22:507–522. doi: 10.3233/JAD-2010-100234. [DOI] [PubMed] [Google Scholar]
  • [51].van Bruggen T, Stieltjes B, Thomann PA, Parzer P, Meinzer HP, Fritzsche KH. Do Alzheimer-specific microstructural changes in mild cognitive impairment predict conversion? Psychiatry Res. 2012;203:184–193. doi: 10.1016/j.pscychresns.2011.12.003. [DOI] [PubMed] [Google Scholar]
  • [52].Nowrangi MA, Lyketsos CG, Leoutsakos JM, Oishi K, Albert M, Mori S, et al. Longitudinal, region-specific course of diffusion tensor imaging measures in mild cognitive impairment and Alzheimer’s disease. Alzheimers Dement. 2013;9:519–528. doi: 10.1016/j.jalz.2012.05.2186. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [53].Fellgiebel A, Dellani PR, Greverus D, Scheurich A, Stoeter P, Muller MJ. Predicting conversion to dementia in mild cognitive impairment by volumetric and diffusivity measurements of the hippocampus. Psychiatry Res. 2006;146:283–287. doi: 10.1016/j.pscychresns.2006.01.006. [DOI] [PubMed] [Google Scholar]
  • [54].Mielke MM, Kozauer NA, Chan KC, George M, Toroney J, Zerrate M, et al. Regionally-specific diffusion tensor imaging in mild cognitive impairment and Alzheimer’s disease. Neuroimage. 2009;46:47–55. doi: 10.1016/j.neuroimage.2009.01.054. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [55].Charlton RA, Schiavone F, Barrick TR, Morris RG, Markus HS. Diffusion tensor imaging detects age related white matter change over a 2 year follow-up which is associated with working memory decline. J Neurol Neurosurg Psychiatry. 2010;81:13–19. doi: 10.1136/jnnp.2008.167288. [DOI] [PubMed] [Google Scholar]
  • [56].Mielke MM, Okonkwo OC, Oishi K, Mori S, Tighe S, Miller MI, et al. Fornix integrity and hippocampal volume predict memory decline and progression to Alzheimer’s disease. Alzheimers Dement. 2012;8:105–113. doi: 10.1016/j.jalz.2011.05.2416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [57].Vemuri P, Wiste HJ, Weigand SD, Shaw LM, Trojanowski JQ, Weiner MW, et al. MRI and CSF biomarkers in normal, MCI, and AD subjects: diagnostic discrimination and cognitive correlations. Neurology. 2009;73:287–293. doi: 10.1212/WNL.0b013e3181af79e5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [58].Vemuri P, Wiste HJ, Weigand SD, Shaw LM, Trojanowski JQ, Weiner MW, et al. MRI and CSF biomarkers in normal, MCI, and AD subjects: predicting future clinical change. Neurology. 2009;73:294–301. doi: 10.1212/WNL.0b013e3181af79fb. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [59].Vemuri P, Wiste HJ, Weigand SD, Knopman DS, Trojanowski JQ, Shaw LM, et al. Serial MRI and CSF biomarkers in normal aging, MCI, and AD. Neurology. 2010;75:143–151. doi: 10.1212/WNL.0b013e3181e7ca82. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [60].Fjell AM, Walhovd KB, Fennema-Notestine C, McEvoy LK, Hagler DJ, Holland D, et al. CSF biomarkers in prediction of cerebral and clinical change in mild cognitive impairment and Alzheimer’s disease. J Neurosci. 2010;30:2088–2101. doi: 10.1523/JNEUROSCI.3785-09.2010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [61].Villain N, Fouquet M, Baron JC, Mezenge F, Landeau B, de La Sayette V, et al. Sequential relationships between grey matter and white matter atrophy and brain metabolic abnormalities in early Alzheimer’s disease. Brain. 2010;133:3301–3314. doi: 10.1093/brain/awq203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [62].Karow DS, McEvoy LK, Fennema-Notestine C, Hagler DJ, Jr, Jennings RG, Brewer JB, et al. Relative capability of MR imaging and FDG PET to depict changes associated with prodromal and early Alzheimer disease. Radiology. 2010;256:932–942. doi: 10.1148/radiol.10091402. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [63].Selnes P, Aarsland D, Bjornerud A, Gjerstad L, Wallin A, Hessen E, et al. Diffusion tensor imaging surpasses cerebrospinal fluid as predictor of cognitive decline and medial temporal lobe atrophy in subjective cognitive impairment and mild cognitive impairment. J Alzheimers Dis. 2013;33:723–736. doi: 10.3233/JAD-2012-121603. [DOI] [PubMed] [Google Scholar]
  • [64].Brewer JB. Fully-automated volumetric MRI with normative ranges: translation to clinical practice. Behav Neurol. 2009;21:21–28. doi: 10.1155/2009/616581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [65].Sperling R. Functional MRI studies of associative encoding in normal aging, mild cognitive impairment, and Alzheimer’s disease. Ann N Y Acad Sci. 2007;1097:146–155. doi: 10.1196/annals.1379.009. [DOI] [PubMed] [Google Scholar]
  • [66].Clark VH, Resnick SM, Doshi J, Beason-Held LL, Zhou Y, Ferrucci L, et al. Longitudinal imaging pattern analysis (SPARE-CD index) detects early structural and functional changes before cognitive decline in healthy older adults. Neurobiol Aging. 2012;33:2733–2745. doi: 10.1016/j.neurobiolaging.2012.01.010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [67].Wee CY, Yap PT, Zhang D, Denny K, Browndyke JN, Potter GG, et al. Identification of MCI individuals using structural and functional connectivity networks. Neuroimage. 2012;59:2045–2056. doi: 10.1016/j.neuroimage.2011.10.015. [DOI] [PMC free article] [PubMed] [Google Scholar]

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