title: Longitudinal study of callosal microstructure in the normal adult aging brain using quantitative DTI fiber tracking.
abstract: We present a review of neuroimaging studies of normal adult aging conducted with diffusion tensor imaging (DTI) and data from one of the first longitudinal studies using DTI to study normal aging. To date, virtually all DTI studies of normal adult aging have been cross-sectional and have identified several patterns of white matter microstructural sparing and compromise that differentiate regional effects, fiber type, and diffusivity characteristics: (1) fractional anisotropy (FA) is lower and mean diffusivity is higher in older than younger adults, (2) aging is characterized by an anterior-to-posterior gradient of greater-to-lesser compromise also seen in superior-to-inferior fiber systems, and (3) association fibers connecting cortical sites appear to be more vulnerable to aging than projection fibers. The results of this longitudinal study of the macrostructure and microstructure of the corpus callosum yielded a consistent pattern of differences between healthy, young (20s to 30s) and elderly (60s to 70s) men and women without change over 2 years. We then divided the fibers of the corpus callosum into the midsagittal strip and the lateral distal fibers in an attempt to identify the locus of the age-related differences. The results indicated that, on average, mean values of FA and longitudinal diffusivity (lambdaL) were lower in the distal than midsagittal fibers in both groups, but the age effects and the anterior-to-posterior gradients were more pronounced for the distal than midsagittal fibers and extended more posteriorly in the distal than midsagittal fibers. Despite lack of evidence for callosal aging over 2 years, ventricular enlargement occurred and was disproportionately greater in the elderly relative to the young group, being 8.2% in the elderly but only 1.2% in the young group. Thus, different brain regions can express different rates of change with aging. Our longitudinal DTI data indicate that normal aging is associated with declining FA and increasing diffusivity in both lambdaL (longitudinal diffusivity) and lambdaT (transverse diffusivity), perhaps defining the normal ontological condition rather than a pathological one, which can be marked by low FA and low diffusivity.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California 94305-5723, USA. edie@stanford.edu
authors.forename: Edith V
authors.initials: EV
authors.lastname: Sullivan
authors.forename: Torsten
authors.initials: T
authors.lastname: Rohlfing
authors.forename: Adolf
authors.initials: A
authors.lastname: Pfefferbaum
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D000704:Analysis of Variance; D016880:Anisotropy; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping; D003337:Corpus Callosum / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D006801:Humans; D020547:Lateral Ventricles / Q000473:pathology; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D055815:Young Adult
references.citation: Neuropsychology. 1998 Jan;12(1):95-114
references.pmid: 9460738
references.citation: Cereb Cortex. 2008 Feb;18(2):433-42
references.pmid: 17575289
references.citation: Magn Reson Med. 2002 Nov;48(5):826-37
references.pmid: 12417997
references.citation: Neuroscientist. 2004 Aug;10(4):372-92
references.pmid: 15271264
references.citation: Eur Radiol. 2008 Jan;18(1):130-7
references.pmid: 17701181
references.citation: Acta Radiol. 2001 Sep;42(5):447-58
references.pmid: 11552881
references.citation: J Psychiatr Res. 1975 Nov;12(3):189-98
references.pmid: 1202204
references.citation: Neurobiol Aging. 2007 Jul;28(7):1075-87
references.pmid: 16774798
references.citation: J Comp Neurol. 2003 May 26;460(2):238-54
references.pmid: 12687688
references.citation: Eur J Radiol. 2003 Mar;45(3):223-34
references.pmid: 12595107
references.citation: AJNR Am J Neuroradiol. 1998 Oct;19(9):1636-8
references.pmid: 9802484
references.citation: J Magn Reson Imaging. 2004 Aug;20(2):216-27
references.pmid: 15269946
references.citation: Radiology. 2000 Sep;216(3):672-82
references.pmid: 10966694
references.citation: Br J Radiol. 2007 Dec;80 Spec No 2:S99-108
references.pmid: 18445750
references.citation: Magn Reson Imaging. 2007 Feb;25(2):154-67
references.pmid: 17275609
references.citation: AJR Am J Roentgenol. 2000 Aug;175(2):425-30
references.pmid: 10915688
references.citation: Eur Radiol. 2003 Jan;13(1):6-11
references.pmid: 12541104
references.citation: Neurobiol Aging. 2005 Oct;26(9):1261-70; discussion 1275-8
references.pmid: 16005549
references.citation: Brain. 2007 Jan;130(Pt 1):48-64
references.pmid: 16959813
references.citation: Neuropsychology. 2007 May;21(3):363-70
references.pmid: 17484599
references.citation: Alcohol Clin Exp Res. 2000 Aug;24(8):1214-21
references.pmid: 10968660
references.citation: Psychiatry Res. 2006 Mar 31;146(2):157-70
references.pmid: 16500088
references.citation: Neuropsychopharmacology. 2005 Feb;30(2):423-32
references.pmid: 15562292
references.citation: Cereb Cortex. 1997 Apr-May;7(3):268-82
references.pmid: 9143446
references.citation: Psychiatry Res. 2007 Apr 15;154(3):253-8
references.pmid: 17321725
references.citation: Cereb Cortex. 2007 Dec;17(12):2760-8
references.pmid: 17307759
references.citation: J Neurosci. 2003 Apr 15;23(8):3295-301
references.pmid: 12716936
references.citation: Neurobiol Aging. 2004 Feb;25(2):175-83
references.pmid: 14749135
references.citation: Nat Neurosci. 1999 Oct;2(10):859-61
references.pmid: 10491602
references.citation: J Neurol Neurosurg Psychiatry. 2000 Feb;68(2):242-4
references.pmid: 10644799
references.citation: AJNR Am J Neuroradiol. 2002 Feb;23(2):194-9
references.pmid: 11847041
references.citation: Neurobiol Aging. 2008 Jul;29(7):1070-9
references.pmid: 17383774
references.citation: Alcohol Clin Exp Res. 2006 Jun;30(6):1045-50
references.pmid: 16737464
references.citation: Neuroimage. 2002 Mar;15(3):708-18
references.pmid: 11848714
references.citation: Magn Reson Med. 2003 Jan;49(1):193-7
references.pmid: 12509838
references.citation: Psychol Aging. 1996 Dec;11(4):621-37
references.pmid: 9000294
references.citation: Neuropsychol Rev. 2009 Dec;19(4):415-35
references.pmid: 19705281
references.citation: Exp Brain Res. 2000 Jul;133(1):66-70
references.pmid: 10933211
references.citation: Neurobiol Aging. 2004 Feb;25(2):185-92
references.pmid: 14749136
references.citation: J Neurol Sci. 2004 Oct 15;225(1-2):33-7
references.pmid: 15465083
references.citation: Nat Rev Neurosci. 2003 Jun;4(6):469-80
references.pmid: 12778119
references.citation: Brain Res. 2007 Apr 20;1142:189-205
references.pmid: 17335783
references.citation: AJR Am J Roentgenol. 1987 Aug;149(2):351-6
references.pmid: 3496763
references.citation: Neurosci Biobehav Rev. 2006;30(6):730-48
references.pmid: 16919333
references.citation: Biophys J. 2005 Nov;89(5):2927-38
references.pmid: 16100258
references.citation: Neuroimage. 2003 Sep;20(1):22-33
references.pmid: 14527567
references.citation: Arch Gen Psychiatry. 1998 Oct;55(10):905-12
references.pmid: 9783561
references.citation: Neuroreport. 1996 Jul 29;7(11):1761-4
references.pmid: 8905659
references.citation: Neurobiol Aging. 2001 Jul-Aug;22(4):581-94
references.pmid: 11445259
references.citation: Neuropsychologia. 2003;41(14):1929-41
references.pmid: 14572526
references.citation: Neurology. 2001 Aug 28;57(4):632-8
references.pmid: 11524471
references.citation: Electroencephalogr Clin Neurophysiol. 1984 Apr;59(2):85-103
references.pmid: 6200311
references.citation: Magn Reson Med. 2002 Feb;47(2):215-23
references.pmid: 11810663
references.citation: Neuroimage. 2006 Oct 15;33(1):239-51
references.pmid: 16877010
references.citation: Arch Neurol. 1999 Mar;56(3):338-44
references.pmid: 10190825
references.citation: Cereb Cortex. 2006 Jul;16(7):1030-9
references.pmid: 16207932
references.citation: Neuropsychology. 2000 Jul;14(3):341-52
references.pmid: 10928737
references.citation: Magn Reson Med. 2003 May;49(5):953-61
references.pmid: 12704779
references.citation: Magn Reson Med. 1999 Dec;42(6):1123-7
references.pmid: 10571934
references.citation: Magn Reson Med. 1991 Sep;21(1):138-43
references.pmid: 1943671
references.citation: Cereb Cortex. 2004 Apr;14(4):410-23
references.pmid: 15028645
references.citation: Neuropsychobiology. 2007;55(2):96-111
references.pmid: 17587876
references.citation: Radiology. 2008 Apr;247(1):179-88
references.pmid: 18292477
references.citation: Neuron. 2004 Sep 30;44(1):195-208
references.pmid: 15450170
references.citation: Eur J Radiol. 2003 Apr;46(1):53-66
references.pmid: 12648802
references.citation: Magn Reson Imaging. 1999 Oct;17(8):1121-33
references.pmid: 10499674
references.citation: Acta Neurochir Suppl (Wien). 1990;51:207-9
references.pmid: 2089896
references.citation: Neuroimage. 2001 Jul;14(1 Pt 1):21-36
references.pmid: 11525331
references.citation: Neurology. 2006 Jan 24;66(2):217-22
references.pmid: 16434657
references.citation: J Cogn Neurosci. 2002 May 15;14(4):659-71
references.pmid: 12126506
references.citation: J Clin Exp Neuropsychol. 2003 Dec;25(8):1128-53
references.pmid: 14566586
references.citation: AJNR Am J Neuroradiol. 2007 Feb;28(2):226-35
references.pmid: 17296985
references.citation: Cereb Cortex. 2005 Nov;15(11):1676-89
references.pmid: 15703252
references.citation: Neurobiol Aging. 2008 Oct;29(10):1547-55
references.pmid: 17451845
references.citation: NMR Biomed. 2002 Nov-Dec;15(7-8):468-80
references.pmid: 12489096
references.citation: Cereb Cortex. 2002 Apr;12(4):438-45
references.pmid: 11884358
references.citation: Neurobiol Aging. 2007 Jun;28(6):955-63
references.pmid: 16797787
references.citation: Neuroimage. 2005 Jul 1;26(3):891-9
references.pmid: 15955499
references.citation: AJNR Am J Neuroradiol. 2001 Jan;22(1):136-42
references.pmid: 11158899
references.citation: AJNR Am J Neuroradiol. 1995 Feb;16(2):241-51
references.pmid: 7726068
references.citation: NMR Biomed. 1994 Nov;7(7):304-10
references.pmid: 7718430
references.citation: J Gerontol B Psychol Sci Soc Sci. 2007 May;62(3):P187-90
references.pmid: 17507587
references.citation: Neuroimage. 2004 Mar;21(3):1174-81
references.pmid: 15006684
references.citation: Brain. 2007 Mar;130(Pt 3):630-53
references.pmid: 17293361
references.citation: Neurobiol Aging. 2005 Aug-Sep;26(8):1215-27
references.pmid: 15917106
references.citation: J Neurosci. 2008 Mar 19;28(12):3227-33
references.pmid: 18354026
references.citation: Magn Reson Med. 2002 Nov;48(5):765-70
references.pmid: 12417990
references.citation: AJNR Am J Neuroradiol. 2000 Jun-Jul;21(6):1078-83
references.pmid: 10871018
references.citation: AJNR Am J Neuroradiol. 2000 Jun-Jul;21(6):1099-109
references.pmid: 10871022
references.citation: Annu Rev Psychol. 1955;6:267-96
references.pmid: 14377367
references.citation: Ann N Y Acad Sci. 2005 Dec;1064:37-49
references.pmid: 16394146
references.citation: J Neurotrauma. 2006 Oct;23(10):1412-26
references.pmid: 17020479
references.citation: Neuroimage. 2002 Nov;17(3):1131-43
references.pmid: 12414255
references.citation: Neuroimage. 2006 Jul 15;31(4):1445-52
references.pmid: 16563802
references.citation: J Neuroimaging. 2001 Oct;11(4):393-400
references.pmid: 11677879
references.citation: Neuroimage. 2008 Mar 1;40(1):77-85
references.pmid: 18226549
references.citation: Biol Psychiatry. 2006 Feb 15;59(4):364-72
references.pmid: 16125148
references.citation: IEEE Trans Inf Technol Biomed. 2003 Mar;7(1):16-25
references.pmid: 12670015
references.citation: AJNR Am J Neuroradiol. 2001 Jun-Jul;22(6):1161-7
references.pmid: 11415913
references.citation: Radiology. 1999 Sep;212(3):770-84
references.pmid: 10478246
references.citation: Neurobiol Aging. 2004 Mar;25(3):377-96
references.pmid: 15123343
references.citation: Magn Reson Med. 2004 Jan;51(1):188-93
references.pmid: 14705060
references.citation: Neuroimage. 2008 Jul 1;41(3):657-67
references.pmid: 18442927
references.citation: Neuropsychology. 2007 Mar;21(2):149-57
references.pmid: 17402815
references.citation: Neuroimage. 2008 Jan 15;39(2):566-77
references.pmid: 17951075
references.citation: Psychol Aging. 1992 Dec;7(4):594-601
references.pmid: 1466828
references.citation: Magn Reson Med. 2000 Aug;44(2):259-68
references.pmid: 10918325
references.citation: J Neurosci. 2005 Jan 19;25(3):604-13
references.pmid: 15659596
references.citation: Magn Reson Med. 1999 Jul;42(1):37-41
references.pmid: 10398948
references.citation: Neurobiol Aging. 2006 Jul;27(7):994-1009
references.pmid: 15964101
references.citation: Neurobiol Aging. 2007 Oct;28(10):1556-67
references.pmid: 16962214
references.citation: Brain. 2008 Feb;131(Pt 2):559-72
references.pmid: 18083753
references.citation: NMR Biomed. 2002 Nov-Dec;15(7-8):456-67
references.pmid: 12489095
references.citation: Brain Res. 1992 Dec 11;598(1-2):143-53
references.pmid: 1486477
references.citation: Neuropathol Appl Neurobiol. 1980 Mar-Apr;6(2):119-32
references.pmid: 7374914
references.citation: Neuron. 2006 Sep 7;51(5):527-39
references.pmid: 16950152
references.citation: Arch Neurol. 2008 Jan;65(1):113-20
references.pmid: 18195148
references.citation: Arch Neurol. 1994 Sep;51(9):874-87
references.pmid: 8080387
references.citation: Neuroimage. 2002 Oct;17(2):657-69
references.pmid: 12377141
references.citation: Neuroimage. 2001 Jun;13(6 Pt 1):1174-85
references.pmid: 11352623
references.citation: Neuroreport. 2003 Mar 3;14(3):345-9
references.pmid: 12634481
references.citation: Magn Reson Med. 2001 Jan;45(1):1-9
references.pmid: 11146478
references.citation: Neurobiol Aging. 2010 Mar;31(3):464-81
references.pmid: 18495300
references.citation: Neuroimage. 2004 Apr;21(4):1428-42
references.pmid: 15050568
references.citation: Cortex. 2003 Sep-Dec;39(4-5):1107-28
references.pmid: 14584569
references.citation: Ann N Y Acad Sci. 1992 Dec 26;673:260-9
references.pmid: 1485724
references.citation: Neuroimage. 2008 Feb 15;39(4):1918-25
references.pmid: 18060810
references.citation: Magn Reson Med. 1996 Dec;36(6):893-906
references.pmid: 8946355
references.citation: Phys Med Biol. 2007 Apr 7;52(7):R57-90
references.pmid: 17374909
references.citation: Neuroreport. 2001 Jun 13;12(8):1677-81
references.pmid: 11409738
references.citation: Neurobiol Aging. 2007 Mar;28(3):459-76
references.pmid: 16500004
references.citation: Nat Neurosci. 2006 Apr;9(4):534-42
references.pmid: 16547512
references.citation: Neuroimage. 2009 Feb 1;44(3):1050-62
references.pmid: 18977450
references.citation: J Neurol Neurosurg Psychiatry. 2007 May;78(5):491-6
references.pmid: 17028118
references.citation: NMR Biomed. 1995 Nov-Dec;8(7-8):333-44
references.pmid: 8739270
references.citation: Amyotroph Lateral Scler. 2007 Dec;8(6):348-55
references.pmid: 17924235
references.citation: Proc SPIE Int Soc Opt Eng. 2008;6914:691409
references.pmid: 19183706
references.citation: Neuroimage. 2002 Nov;17(3):1429-36
references.pmid: 12414282
references.citation: Neurobiol Aging. 2006 Dec;27(12):1827-33
references.pmid: 16310892
references.citation: J Neurol Neurosurg Psychiatry. 2005 Feb;76(2):200-5
references.pmid: 15654032
references.citation: Neuropsychology. 2007 Jul;21(4):412-8
references.pmid: 17605574
references.citation: Magn Reson Med. 1998 Jun;39(6):928-34
references.pmid: 9621916
references.citation: Neuroreport. 2001 Jan 22;12(1):99-104
references.pmid: 11201100
references.citation: Neurology. 1998 Apr;50(4):972-8
references.pmid: 9566381